1 Introduction

In earlier days, the conventional forms of drug administration were generally ointments, pills, solutions that can be injected into the bloodstream, or by oral solutions. At present, various drug delivery approaches have been developed, for example, chemical modification of drugs, entrapment of drugs in inorganic and organic materials that are placed in desired body parts, or drug entrapment in small intravenous vehicles. Drug delivery systems are those for the delivery of drugs to the target sites where therapeutic actions are to be carried out. The technologies implemented for these applications include those regarding the route of administration, drug preparation, site targeting, and toxicity. The dosage form is based on the route of administration and enteral, parenteral (injections), transdermal, inhalation, oral, and topical routes are some of the habitual routes of administration. One of the problems encountered while administering drugs is the molecular size of drug particles. Due to molecular size and charge, many medications like peptide and protein, gene, vaccine, and antibody-based drugs, may not be supplied using these routes because it cannot be absorbed into the systemic circulation effectively. The solubility of drugs also plays a vital role in drug efficacy, independent of the administration route. To avoid this problem, drug carrier materials have been used in the medical field to deliver the therapeutic molecule at specific sites in the human body. However, there are many problems still existing in drug delivery systems, such as low drug loading efficiency, rapid release, degradation rate, size, and various other surface chemistry hurdles are still some of the roadblocks and challenges after its administration to our body. There are numerous standard bulk methods to synthesize drug delivery systems, but they all suffer from several drawbacks. The constraints in generating carriers that are to be loaded with multiple therapeutic agents, studying the therapeutic/toxic effects in vivo, and the difficulty confronted in localized drug delivery can be considered as some drawbacks.

Recently, the field of nanotechnology has acquired a lot of attention for its ability to effectively diagnose and take care of various kinds of tumours. Nanocarriers are colloidal drug carrier systems having submicron particle sizes typically, less than 500 nm [1]. For the past few decades, they have been comprehensively examined as they exhibited promising results in the area of drug delivery. Nowadays, nanocarriers of size less than 100 nm have been developed. Nanocarriers have the capability of altering the fundamental properties and bioactivity of the drugs, due to their high surface area to volume ratio [2]. Nanocarrier systems own several advantageous aspects for the intended areas of applications. The volumes of distribution are lowered when the drugs and imaging agents are combined with nanocarriers. And it also can improve the pharmacokinetics and intensify the distribution of therapeutic agents to target organs, which results in better effectiveness. The drug toxicity is abridged as an outcome of its preferential accretion at the specific destinations and lower levels of concentration in the healthy tissues. Many nanoscale carriers also have the enviable advantage of enhancing the solubility of hydrophobic compounds in the aqueous medium to make them appropriate for parenteral administration. Moreover, to be on the safer side, biocompatible nanocarrier materials are being used recently [3].

The substantial amount of effort taken in the synthesis and modification of nanomaterials has resulted in the advancement of the utilization of nanoparticles for various biomedical applications such as gene/drug delivery, orthopedic implants, tissue engineering [4, 5], bone regeneration, magnetic resonance imaging (MRI), and cancer treatment [6, 7]. Nanoparticle-based drug delivery systems have arisen as an assuring methodology for the improvement of the efficiency of prevailing drugs and also to enable the advancement of new therapies. Various characteristics like size, porosity, morphology, adsorption, and physicochemical parameters determine the suitability of nanoparticles for their usage in drug delivery systems. Nanoparticles have the potential and ability to navigate through the body’s smallest blood vessels effectively and securely due to miniaturization and associated technology developments. Also, it increases the surface area for rapid dissolution of the drug. Porosity is essential for capturing gases in the nanoparticles, for the controlled release rate of the drug, and also for targeting the drugs to specified sites [8].

2 Inorganic and organic nanoparticles

2.1 Organic nanoparticles

In general, nanoparticles can be classified into two: Organic and Inorganic. Organic nanoparticles (eg: Micelles, dendrimers, ferritin, liposomes, and so on) are non-toxic and biodegradable. It also has to be highlighted that nanocapsules for example like micelles and liposomes, which have a hollow core, are delicate to thermal or electromagnetic (EM) radiations such as heat and light. These exceptional features make them a perfect choice for biomedical applications, drug delivery in particular [9]. Nevertheless, certain factors like poor stability, short shelf life and low drug encapsulation efficacy, could hinder their widespread utilization in drug delivery applications, as reported by Naseri et al. [10]. A comparison on the properties of organic and inorganic nanoparticles [11], that play a key role in determining their utilization as drug carriers, is given in Table 1.

Table 1 A comparison on the physical and biological properties of organic and inorganic nanoparticles
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2.2 Inorganic nanoparticles

Inorganic nanoparticles are highly stable and hydrophilic when compared to organic nanomaterials [16]. Inorganic nanoparticles do have intrinsic outstanding physicochemical properties (magnetic, thermal, optical, and catalytic performance) and therefore, these nanosized materials offer a sturdy framework where two or more dopants can be integrated to give multifunctional abilities [

3 The necessity of drug delivery applications

In recent days, researchers have been more keenly concentrated on the improvement of the safety efficacy ratio of the existing drugs rather than develo** a new drug that requires a huge amount of money and time. The improvisation methodologies include procedures like monitoring the drug, the drug dosage, individualization of drug therapy, slow and controlled delivery of the drug, and targeted drug delivery. The principles of pharmacodynamics and pharmacokinetics, which manage the action and character of drugs, were thoroughly studied on administering these improvised drugs on living beings. From these studies, it was found that nasal and buccal mucosa and also skin membranes can be utilized as the alternate routes for the delivery of analgesics and anaesthetics. Similarly, when these drugs were combined with other materials, a whole new range of implantable and programmable devices such as nasal aerosol sprays, transdermal and transmucosal delivery systems, incorporated with controlled drug release technology, were developed. The obstacles faced while using the standard methods of drug administration can be subjugated by implementing these methods.

In most cases, the efficiency of the drug carrier is highly dependent on the particle size, i.e., smaller the particle size, the greater the surface area and therefore has a greater capability to cross the minute parts in the human body like the blood–brain barrier and constricted junctions in the endothelial cells in the skin. The drug particles may also exhibit increased bioavailability and higher solubility. There are some basic requirements to be achieved for the designing of an ideal drug carrier for higher drug efficacy. The first and foremost one is that, when administered, the loaded drugs should reach the destination site with minimum volume loss and blood circulation activity. The next requirement is that the drug administered should only act on the desired tumour site and should be ineffective to the healthy cells.

3.1 Types of drug delivery and the utilization of inorganic nanoparticles

3.1.1 Pulmonary drug delivery

Intake of medications via inhalation has been available for many years for treating respiratory diseases. Inhalation is found to be an optimal and non-invasive route of administration for first-line therapy of asthma and other chronic obstructive pulmonary diseases. Also, lungs are capable of absorbing medications for systemic delivery, like drug delivery for diseases such as diabetes mellitus since lungs have a large surface area for absorption, high permeability, and an excellent supply of blood. The main absorption site, for most of the pharmaceuticals in the lungs, is the alveolar epithelium in the central part of the lung (Fig. 2 A). The epithelial cells in the respiratory system play a key role in regulating the airway tone and also in producing the lining fluid in the airway.

Fig. 2
figure 2

A Administration of drugs into lungs using nanoparticle-based drug carriers. B (a) Cytotoxicity of GO, GO-PEG and GO-PEG-MAN on human THP-1 cells. (b) Cellular uptake of C6@GO-PEG and C6@GO-PEG-MAN by THP-1 cells after 1 h incubation. (c) Effects of free mannose on the cellular uptake of C6@GO-PEG-MAN in THP-1 cells. (d) Cellular uptake of C6@GOPEG-MAN in THP-1 cells under different endocytosis inhibition conditions. (e) Confocal images for intracellular localization of C6@GO-PEG-MAN and lysosomes in THP-1 cells at 1 h, 3 h, 6 h and 12 h. TEM images for localization of (f, g) GO-PEG-MAN in lysosomes of THP-1 cells, and (h, i) GO-PEG-MAN and M.tuberculosis (H37Rv) in the H37Rv infected THP-1 cells. Adapted with permission from [164]. © 2019 Elsevier Ltd. All rights reserved. C) (a) Cellular uptake of [46Sc] Sc-HAp and [46Sc] Sc-HAp-Zr in A549 cell line at 10, 30, and 60 min. (b) Ex vivo biodistribution of Sc-46, [46Sc] Sc-HAp, and [46Sc] Sc-HAp-Zr in normal mice 1 h after injection. Adapted with permission from [165]. © 2021 Elsevier Ltd. All rights reserved

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For appropriate therapeutic efficacy, if the lung is the target organ or the route of administration, a suitable amount of drug should be deposited in or around the oropharynx. In addition to the deposition site, the uniformity in the distribution of drugs is also a major factor for drug efficacy. At present, there are a number of inhaled products in the market to treat respiratory diseases. This drastic growth in the usage of inhalable drugs is due to the increased development of inhalable devices (nanoparticles or aerosols) that are capable of delivering high doses of the drug to the respiratory pathway, with higher deposition efficacy, when compared to earlier methods of administration. The capability to defeat the first-pass metabolism and low enzymatic activity are some other advantages of these newly developed inhalable devices over the traditional or peroral applications of therapeutics. When the lung is selected as the route of administration, there is a need to have some basic knowledge of the science behind the pulmonary drug delivery, i.e., physiological characteristics (respiratory pathway geometry, size of the particle, polymer selection) and other technicalities that affect the therapeutic efficiency.

There are various natural defence mechanisms like the bronchial tree, for the human lungs to prevent the entry of aerosol particles. Bronchial tree or the oropharynx are known to be very good filters that eliminate the inhaled aerosol particles and also prevent the deposition of particles in the epithelium. So, the administered drug delivery system should surpass these filters. In addition to these filters, there are some other precautionary mechanisms that inhibit the permeability of the drug into the circulatory system and cause an obstacle for the cellular uptake. It is said that, by principle, the absorption property of the substances that are inhaled greatly depends on their properties like molecular weight, charge, and solubility. Compared to the larger molecules, smaller ones are absorbed more quickly. For inhalation, the nanoparticles should possess a pH value above 3 and below 8.5, excellent aerosol properties, and should be sterile. There are few strategies followed to overcome the challenges faced during the development of inhalable therapeutic drugs using nanocarriers. The first one is the nebulization of nanocarriers in the form of colloidal suspensions. The next one is the association of the developed nanocarrier system with a microsize carrier. This association can be done by implanting the nanoparticle-based carrier into the microsize carrier. It can also be done via the incorporation of inert carriers (eg: Mannitol) onto the nanocarriers.

When we consider the case in which GO is selected as the lung targeting nanocarrier material, it was reported in previous works that the administration can be done through inhalation or IV routes and also reported the positive results based on their uptake by the cells in the lungs [189]. Kumar et al. developed a stable, hybrid nanosystem by electrostatically assembling GO (2D) and graphene QDs (0D) in layers, using PEI as a bridge. Even when exposed to a laser of very low power, the complex system responded exceptionally, concerning the photodynamic and photothermal activity, bioimaging, and oxidative stress in the MDA-MB-231 cell lines [190]. Luo et al. synthesized GO nanosheets loaded with very small SPIONs of diameter less than 5 nm, with the help of Na3C6H5O7 as an inhibitor for crystal growth, which could be utilized for both chemotherapeutics and T1-MRI. Doxorubicin was then modified with generation 2 PAMAM (dendrimer) and cis-aconitic acid since the amino groups can easily form appropriate links with the –COOH groups present on the surface of GO, and this modified DOX was loaded onto the synthesized SPIONs-loaded GO nanosheet. The nanosheet could be used as an efficient drug carrier as it displayed a manageable pH-sensitive release of DOX and better anti-cancer efficiency. Due to the interface formed between the in situ-grown SPIONs and GO, the nanocarrier showed high values of r1 and therefore, excellent performance in the case of T1-MRI in-vivo [191]. Usman et al. also developed a GO-based theranostic drug delivery system in which a natural anticancer drug, Protocatechuic acid, and a contrast medium, GdH12N3O15, were doped onto the GO nanosheet surface through pi stacking and H-bond formations. Later, via electrostatic interactions, gold nanoparticles were adsorbed onto the functionalized nanosheet. The release of the drug was reportedly higher in an acidic environment, and the nanocarrier was non-toxic to normal fibroblasts. A visible increase in the T1-contrast of the developed nanosheet suggested that they could be used as efficient agents for MRI [192]. Further research has to be done here since the results are completely based on the experiments done in-vitro. Guo et al. developed a uniform-sized nanoplatform for the combined photothermal chemotherapy. The nanosystem consisted of rGO onto which mSiO2 was grown through the formation of a supramolecular interface, and PEG-modified-Octadecanoic acid was added in order to make the nanoplatform more stable and soluble. Finally, via non-covalent bonding, DOX was loaded to the nanocarrier system. It was reported that the DOX release was initiated only by an acidic medium and when subjected to light radiation, the nanoplatform exhibited improved as well as combined photothermal and chemotherapeutic effects [193]. Another work based on GO was done by Liu et al. in which, GO was PEGylated and then loaded with a 2-photon compound (BL4) and photosensitizer (PPa) simultaneously, for the combined photothermal and photodynamic therapies. The 2-photon compound was found to be capable of converting the incoming light in the NIR region (980 nm) to the light in the visible region and therefore attained a greater, extended therapeutic efficacy. GO quenches the photoactivity of the 2-photon compound and the photosensitizer, but as soon as they are released from the nanocarrier, they are activated. So, the combined therapy with an excitation laser of a single wavelength repressed the large growth of tumour cells and also resulted in lesser damage to the normal cells [194].

The role played by the AgNPs in the field of cancer theranostics is also inevitable. In the work by Debnath et al., AgNPs, whose size could be tuned, were synthesized using the one-step process of vibration milling at high speeds, and in order to reduce the synthesized AgNPs, chitosan, PEG and PVP were utilized instead of surfactants. The particles were found to be stable for a long period and its standard diameters were in the region between 3.1 ± 1.4 nm and 22.8 ± 5.8 nm. They exhibited high levels of cytotoxicity and anticancer characteristics by subduing the growth of MCF-7, NIH-3T3, and NCI-H358 cell lines [195]. Asha et al. developed a nanoparticulate system in which the surface of nanorods of Eu doped HAp was decorated with Ag2+ ions that were passivated with linoleic acid. When annealed at 250ºC, via diffusion, ultra-small AgNPs were formed on the surface of nanorods by nucleation. These biocompatible nanorods exhibited outstanding cytotoxicity against MCF-7 and F929 cancer cell lines. The presence of Ag2+ ions and AgNPs additionally to europium, made the nanorods display varied luminescence i.e., from NIR to visible range emissions, which makes the developed nanosystem ideal for imaging in the deeper areas of tissues [196]. Yao et al. developed an antibody therapeutic system by conjoining AgNPs with Rituxan, which is a well-known monoclonal antibody for lymphoma. This conjoining with AgNPs restricted the entry of Rituxan into the cells and extended the interaction between the cell and drug, which resulted in enhanced therapeutic efficacy. Thus, the designed nanocarrier has transformed the actions of the antibody at the molecular level. They could also be functioned as a sensitive probe, to identify lymphoma cells that are alive, with the help of SERS. In order to increase the efficiency further, the structural features of the nanocarriers can be altered or the amount of antibody involved can be managed [197]. Sakr et al. also prepared 21 nm hydrodynamic sized, PEG capped AgNPs doped with 131I (core–shell), by a unique single-step method. The synthesized particles were found to be highly stable (in-vivo and in-vitro), non-cytotoxic to WI-38 normal cell lines at lower concentrations, enhanced yields from radiolabelling, and improved uptake of tumours. Thus, these particles could be potentially used as nanocarriers for radiotherapeutics in cancer theranostics [198]. Of all the AgNPs shapes, it was conveyed that the Ag nanoprisms exhibit very strong SPR in the NIR region and hence they have greater potentiality for photothermal therapies. But the complication lies in its heavy toxicity and its vulnerability in the physicochemical atmospheres. This inspired Zeng et al. to design a hybrid nanosystem with polydopamine-coated Ag nanoprisms, functionalized with RGD peptide. Polydopamine helps the nanoprisms to stay stable and biocompatible in-vivo, to convert incoming light to heat upon NIR irradiation, and also make the surface ideal for functionalization. So, in short, the developed nanosystem can act as drug delivery system, probe for photothermal therapy and an agent for imaging simultaneously [199].

In the work by Feng et al., SPIONs along with PEG were utilized to encapsulate the mesoporous and hollow copper (II) sulphide nanoparticles, loaded with Doxorubicin. It was noted that the developed nanocarrier system could be effectively controlled with the help of an external magnetic field and also exhibited higher absorption when irradiated using NIR radiation. The efficient encapsulation by the SPIONs resulted in minimal adversities and timely and controlled release of doxorubicin during the in-vivo delivery of drugs. Therefore, the developed system can be used for both photodynamic and photothermal therapies at the same time due to the combined effect of hyperthermia and plasmonic resonance [200]. Hayashi et al. developed a biocompatible nanosystem in a core–shell arrangement, in which the core was formed by a cluster of IONPs. In the cluster formed, the distance between the particles was maintained to be zero and this helped in boosting the r2 value and also the power for generating heat. The process of release of drugs was initiated as a response to the varying magnetic field and even when the magnetic field was removed, the release continued. This resulted in the accumulation of nanoparticles in the tumour-site which in turn facilitated the conception of MRI. So, the consequent application of a magnetic field could generate hyperthermia and restricted tumour cell growth. This led to increased therapeutic efficiency with minimum side-effects [201]. As discussed earlier, the presence of IONPs as a core permits its application in imaging and at the same time, the property of AuNPs (as the shell) getting heated when subjected to laser radiations, the action of attachment of drugs onto its surface is inverted. These properties were exploited by Malekigorji et al. and then synthesized a hybrid nanosystem using IONPs and AuNPs, onto which the drug (which is in the bisnaphthalamido-based series) was loaded. A drug release which was activated by heat was attained as a result of the utilization of the electrostatic interaction between the drug and the Au surface [202]. Huang et al. developed a nanoparticle-based system from PEI and PEG-coated SPIONs, modified with folic acid, and then loaded with Doxorubicin (DOX). The DOX release was highest in acidic medium and the nanosystem exhibited outstanding stability. Also, they inhibited the growth of cancer cells with improved efficacy, in the presence of the magnetic field. A higher value of r2 was shown while monitoring the accumulation of the nanoparticles around the tumour cells, using MRI [203]. Aeineh et al. also developed a delivery system by functionalizing spherical IONP-surface with Glutathione and PEI for delivering Curcumin. The nanosystem exhibited excellent biocompatibility and increased cellular uptake [204]. Gao et al. developed a similar biocompatible nanocarrier using IONPs that were functionalized using folic acid, PLGA, a cell-penetrable peptide, and Doxorubicin. Due to the presence of the peptide, the level of toxicity was significantly reduced and was also having the exceptional ability for tumour-specific targeting. This nanosystem was also capable of encouraging ROS production which resulted in cell apoptosis. They could also be utilized as a probe for MRI r2* map** [\(\upmu\)M) of PTX for 48 h without any stimulus. In the presence of a strong magnetic field, the carrier system exhibited a much higher (four-fold) therapeutic efficacy when compared with conventional chemotherapy using Temozolomide [227].

For the upcoming progressions in treating psychiatric and neurological diseases, there is a need for neuropeptides with targeting capability. But the difficulty here is the inability of such peptides to capably crossing the BBB. ASV-30, from earlier studies, is one such peptide which helps in reducing typical anxiety behaviours by acting upon the CRF2 expressing neurons when used directly. Vinzant et al. verified whether the iron oxide nanoparticles conjugated with ASV-30 could travel across BBB, localizes the CRF2 receptors, and could reduce anxiety. They were successful in their research since there was an enhancement in the bioavailability of ASV-30 by the thorough administration of the iron oxide-peptide (ASV-30) complex nanoparticles. This study helped in introducing a new method for the delivery of peptides, across BBB, with high efficiency and biodistribution [228]. Saesoo et al. developed SPIONs functionalized with liposomes (Fig. 4C(a)), the drug Rituximab and tween80 (for improved penetration of BBB), which was aimed to easily travel across BBB and treat CNS lymphoma. The drug carrier system exhibited higher monitoring abilities, improved delivery of drugs, and was also capable of diagnosis. Also, the spherical-shaped particles of diameter between 140 and 190 nm, showed the property of super-paramagnetism (Fig. 4C(b)). Thus, the developed system could be used as a theranostic tool, which could easily transit across BBB and focus around the cancer cells (Fig. 4C (c, d)). This was one of the first nanoparticle-based theranostic systems ever developed for treating CNS lymphoma [223].

Another temperature-sensitive, Doxorubicin encapsulated liposomal nanosystem was designed by Shi et al., which is capable of crossing BBB and delivers drugs for treating aggressive tumours like GBM. The drug, doxorubicin, and SPIONs were loaded up simultaneously to a liposomal system containing Tenascin-C (antibody) and P1NS (a peptide that is capable of targeting GBM and has high permeability through cells). The results proved that the liposomal delivery system was not eliminated by the endothelial cells and at the same time was capable of targeting and entering the glioblastoma cells. The investigation on the passage of the synthesized delivery system through BBB was done in an in-vitro model and prominent outcomes, like the noticeable value of TEER and expressions of tight junctions, was observed. In the presence of a varying magnetic field, the SPIONs inside the delivery system caused a thermally activated release of doxorubicin, which was controlled, effective, and was also less cytotoxic to normal cells [229]. Shen et al. also worked on develo** a nanocarrier, which could easily pass through BBB, act as a probe for imaging, and can function as a theranostic tool, for treating glioma. The nanosystem consisted of hydrophobic SPIONs coated with DSPE-PEG2000, Doxorubicin, and a cyanine dye – ICG. The as-synthesized nanoparticle system was of suitable size (22.9 nm diameter), and thus an effectual uptake of doxorubicin by the cells was observed, without any side-effects. The nanoparticles were able to successfully travel across BBB and were also seen gathering around the tumour cells, in particular, which was observed from the MRI and fluorescence imaging [230]. Shaghaghi et al. designed a multifunctional, SPIONs and folic acid incorporated, Janus-based nanocarrier that could deliver doxorubicin across BBB to the tumour cells in the brain. The surface of Janus nanoparticles is said to have more than 2 physical characteristics and allows 2 separate kinds of chemistry to happen simultaneously. The folic acid conjugated covalently to the Janus nanoparticle acts as an agent for targeting the cancer cells. The developed drug carrier system showed an increased circulation period in blood. Since the doxorubicin was conjugated covalently to the system through imine bonds, a pH-sensitive release of doxorubicin was initiated [231]. Next is the work done by Norouzi et al., on the development of a biocompatible, magnetically targeting vehicle for the delivery of Salinomycin to the brain, for the treatment of GBM. Iron oxide nanoparticles were combined with PEG and PEI and then the drug was loaded onto this system. The release of the drug from the delivery system was prolonged for about four days, in acidic conditions, and was found to be efficient in killing the ROS (reactive oxygen species) mediated GBM cells. The BBB permeability of the Salinomycin-PEI-PEG-Iron Oxide nanoparticle-based system was only about 1.0% ± 0.08%, but in the presence of an external magnetic field and also with hyperosmotic disruption, the permeation ability increased to 3.2% ± 0.1% [232].

When a stroke happens, an excess amount of ROS is produced and they could destroy the BBB. As far as Nanoceria is concerned, they are found efficient in scavenging ROS and offer high protection to the neurons and vasculature of the brain. Bao et al. designed and developed a neuroprotective nanocarrier to effectively deliver the therapeutics required for the treatment of strokes. The nanosystem consisted of CeO2 nanoparticles functionalized with PEG and an oligopeptide, Angiopep-2, and was loaded with the drug, Edaravone. This system was non-toxic, was able to cross BBB through transcytosis, and at the same time, was successful in ensuring the stability of the environment of the brain. A high level of agglomeration of particles was found in the intracerebral lesions. This nanoparticle system could, therefore, be used for the targeted delivery of drugs for treating neurodegenerative diseases [233]. Kaushik et al. computationally analyzed the effectiveness of ceria nanoparticle-based drug delivery systems in elucidating the activity of α-synuclein (causing Parkinson’s disease), when compared to that of the SPIONs and AuNPs. It was found that CeO2 nanoparticles were capable enough to inhibit α-synuclein activity [234]. In a recent attempt by Lin et al., honokiol loaded HAp nanoparticles were developed for targeted delivery of the drug, during the post-glioma surgery management. It was noted that in acidic environment, the hydrophobic honokiol-HAp nanoparticles undergo burst release. The nanoparticle system also displayed better cell viability along with prolonged and effective release of honokiol. Additionally, after the treatment with honokiol loaded HAp, the MRI results of the in-vivo studies carried out, displayed an effective reduction of the size of tumor by 40% [235].

3.1.4 Ocular drug delivery

The human eye is a very complicated organ with distinctive physiology and anatomy, and therefore, the designing of an ideal drug carrier for the eye, that targets a certain tissue, has been a greater challenge for the researchers. The interior of the eye consists of three parts: anterior and posterior chambers, and vitreous body. The tissues like cornea, iris, and lens, together form the anterior chamber. The posterior chamber is made of tissues like the choroid and sclera. Different types of vision-affecting diseases, for example, cataract, conjunctivitis, diabetic retinopathy, and glaucoma, pose a threat to the anterior chamber and posterior chamber. In the eye, the retina is separated from the circulation of blood, by the BRB or Blood-Retinal Barrier. Both the interior and exterior BRB cells consist of tight junctions that differ only in their configuration. These tight junctions control the movement of molecules or fluids between the tissues in the retina and the ocular vasculature. It also prevents the entry of very large molecules and various other foreign, unsafe agents into the retina and supports the retention of the micro-environment in the retina [236]. In addition to this barrier, there are various other barriers, both static and dynamic which are unique and intrinsic to ocular anatomy. Most of these barriers generally protect the eye from toxic agents [237]. Due to these obstructions, it is important to develop a drug carrier for treating retinal diseases with appropriate size range, enhanced drug penetration, controlled drug release, and drug targeting capability with minimal side-effects which ensure high therapeutic efficiency and biocompatibility (Fig. 5 A).

Fig. 5
figure 5

A Various methods of administration of drug-loaded nanocarriers to overcome different ocular barriers B (a) Image of the AuNPs loaded contact lens. (b) Timolol concentration in tear fluid from the blank-4 mg contact lenses (253 ± 3 μg timolol loading), 0.025 mM-GNP-CL-4 mg (277 ± 7 μg timolol loading) and eye drop treatment (1 drop = 250 μg of timolol maleate). The histopathological images of cornea were taken by the light microscopy at X450 magnification. Adapted with permission from [239]. © 2019 Elsevier Ltd. All rights reserved

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In a study by Salem et al., an antifungal drug named Flucytosine was capped by gold nanoparticles and the nanocarrier was developed with the help of liposomes for treating the inflammation of intraocular fluids (endophthalmitis), caused by Candida albicans. AuNPs acted as an agent for contrasting, which helps in tracing the drug in the posterior chamber of the eye. Liposomes were formulated in varying ratios of molar weights. The optimum formulation of liposome was obtained, when stearylamine, phosphatidylcholine, Span 60, and cholesterol were taken at a ratio of 0:1:1:1, with a maximum ocular depth of penetration (10.22 ± 0.11 mm) and maximum drug release (7.043 mg/hour). When Candida albicans infected cornea of rabbit were treated with the as-prepared nanocarrier, it reported an increase in the healing efficiency, since there was an increase in the zeta potential (positive) of the liposome used. The Computed Tomography (CT) imaging technique revealed the achievement in tracking the AuNPs [238]. For prolonged delivery of drugs to the tissues in the eye, contact lenses could be used. But the problem lies in the fact that the inclusion of drugs onto the lens could damage its significant characteristics. There are various methods implemented for loading drugs to contact lenses like molecular imprinting, the technology of supercritical fluids, and soaking methods. Timolol is a medication that helps to treat glaucoma, which is caused by the increased pressure in the eye. Incorporation of timolol to the lens via the standard method of soaking doesn’t expressively change the substantial characteristics of the lens but there is a possibility for burst release and minimal loading of drugs. Maulvi et al. studied the consequences of loading AuNPs on the contact lens, through the conventional method of soaking, and also about its drug-releasing performance. In the first methodology followed, AuNPs were mixed in the soaking solution that contains timolol (GNP-SS), and in the second, the AuNPs were directly fabricated to the lens (GNP-CL) (Fig. 5 B (a)). The in-vivo studies indicated that GNP-CL contained higher concentrations of timolol. The studies on the distribution of drugs also revealed the major enhancement in the deposition of drugs at the desired sites, when GNP-CL was used (Fig. 5B(b)). So, in a nutshell, the author has reported the ability of AuNPs in enhancing the acceptance of drugs from the soaking solution, without affecting the properties of the lens [239]. AuNPs should be highly stable to be more efficient and also to avoid forming clusters in tissues or cells. Masse et al. reported the novel conditions under which highly stable AuNPs were synthesized. The AuNPs were made highly stable by combining it with ligands of mass that range from 800 to 600 g/mol. The research group has also proven the capability of the synthesized nanoparticles in encapsulating the drug used for treating glaucoma, Bimatoprost, from the experiments done for assessing drug encapsulation. The nanoparticles exhibited no cytotoxicity in MTT assay. From the results obtained, the author has concluded that the synthesized ultrastable AuNPs can be utilized as potential drug carriers for ocular therapies [240]. Natesan et al. designed a formulation in which Hypocrellin B, along with AgNPs, was loaded on PLGA (HBS-NPs), which aimed at attaining an increased 1O2 production and can be applied for ocular photodynamic therapy, i.e., for treatments in the posterior chamber of the eye. The HBS-NPs were in the range between 135.6 and 828.2 nm, showed 92.9 ± 1.79% of encapsulation efficacy, contained 2.60 ± 0.06 mg/mL of amorphous Hypocrellin B and exhibited a negative zeta potential. Regarding the release of drugs, a burst release (3.50%) was witnessed in the initial 8 h, which was then followed by a steady release (47.82%), observed for 3 days. An increase in the ROS production by the HBS-NPs was detected, when compared to that of the HB-NPs or pure HB. When HBS-NPs were irradiated by the light source, it showed phototoxicity which depended on time and concentration [241].

Typically, the RPE cells are held responsible for causing blindness in both adults and children. From the report of Giannaccini et al., effective utilization of magnetic nanoparticles as drug carriers made it possible to rapidly and specifically locate the RPE cells. Additionally, this nanocarrier could be used to offer therapies in those areas which have the least access and can also be used as an agent for tracking in MRI, in various kinds of retinopathy [242]. Mousavikhamene et al. introduced an exceptional method for delivering drugs from the periocular routes, across the sclera, with the help of magnetically subtle nanoparticles that are loaded with drugs. He stated that applying an external magnetic field in front of the eye, after injecting the magnetically-active, polymeric nanoparticles into the periocular space (parallel to the axis of the eye), could influence the nanoparticles so that, they move in the magnetic field direction and travel across the sclera. This method could overcome the difficulties faced by the normal scleral drug nanocarriers. An anti-inflammatory drug, diclofenac sodium, was loaded onto a nanocomposite consisting of sodium alginate (biopolymer) and IONPs. In the presence of an external magnetic field, a substantial upsurge in the transferring of diclofenac sodium through sclera was affirmed [243]. Agban et al. developed a novel nanoparticle cross-linked collagen to overcome the difficulties met while using the usual therapeutics for treating glaucoma. The current practice involves the recurrent usage of eye drops which resulted in reduced healing effects and weak patient compliance. The objective of this research group was a continual delivery of Pilocarpine hydrochloride and surmount the ineffectiveness of the eye drops prescribed for glaucoma. PVP functionalized zinc oxide nanoparticles were selected as ideal delivery candidate when compared with TiO2 and pure ZnO. ZnO/PVP loaded with PHCl, displayed cytotoxicity, thickness, tensile strength, transparency in shielding and bioadhesive properties which are supportive for ocular drug delivery. Zinc ions were also released along with PHCl and the concentration of Zn ions was much lower than the half maximal inhibitory concentration. Also, the drug release from the crosslinked collagen was observed for a stretch of 14 days. This confirmed a sustained PHCl release for the therapy, which is much more extended than the drug release by the administered eye drops [244]. Luo et al. has also introduced a new formulation for the treatment of glaucoma. They have designed a nanocarrier (in the form of eye drops) for targeted and continual delivery of pilocarpine to the eye. Hollow nanoceria was functionalized with ZM241385 and chitosan. They were designed in such a manner so that they can pass through the tight junctions of BRB. The results of the prepared eye drops, when compared to that of the conventional eye drops, showed that the as-prepared nanocarrier had anti-inflammatory and antioxidant characteristics, which are the important criteria for eradicating glaucoma progression. It established 42 times longer period to normalize the elevated pressure, in a one-time administration which, according to the author, attributes to the permeation of the nanocarrier through the cornea [245]. Diabetic cataract is considered as one of the major causes of visual impairment in patients, who are diabetic. There are only a handful of drugs that are capable of prolonging or preventing this type of cataract. Zhou et al. synthesized Nanoceria and coated it with a combination of polyethylene glycol and PLGA to form a redox and auto-reformative nanoparticle. The results affirmed that the nanoparticles remained in the eyes for an extended time and thereby reduced the opacity of the lens which, later on, attenuates diabetic cataract. The author suggested that this advantageous result can be attributed to two reasons; the antioxidant behaviour of the prepared nanoparticles and the action of nanoparticles as an inhibitor of non-enzymatic glycosylation which helps to keep the lens transparent [246].

3.1.5 Drug delivery for microbial infections and wound healing

The chronic wounds and full-thickness burns are extremely vulnerable to infections caused by bacterial growth and their treatment is quite costly. So, their co-operated healing imposes a huge responsibility for the therapeutics. The top-notch approach for enhanced extermination of bacteria can be made by encapsulating the necessitated drugs into the nanoparticulate system. In this way, the efficiency in delivering the drug to the target site and thus the bioavailability of the drug can be enriched, with reduced toxicity (Fig. 6A(a)). Nanoparticles are known to have a large surface area which makes them easier to functionalize, resulting in furthermore increased ability in loading drugs onto its surface. Therefore, nanoparticles exhibit a very high affinity to bacterial growth (Fig. 6A(b)) [247].

Fig. 6
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A (a) The effect of delivery of naked anti-microbial nanoparticles and drug conjugated nanoparticles to the wound site by various methods. (b) The mechanism of antimicrobial activity of anti-microbial nanoparticles. B (a) Photograph of the PAA@rGO electrospun polymeric mat. (b, c) SEM images of S. epidermidis treated with cefepime loaded PAA@rGO mats and irradiation for 5 min and 30 min, respectively. Photographs of (d) wound scars, 24 h after photothermal treatment for 10 min and (e) intact mouse skin and the three representative skin samples after 48 h of infection, under different treatment conditions. Adapted with permission from [256]. Copyright 2018 American Chemical Society. C (a) The confocal images of (i) S. aureus and (ii) E. coli, respectively treated with ZnO and ZnO-CS/Alg. (b) Histological analysis on HE stains and on Masson’s trichrome stain of the ZnO-CS/Alg. group at (i, vi) 3 days, (ii, vii) 7 days, (iii, viii) 14 days, (iv, ix) 21 days, and (v, x) 48 days, respectively. Adapted with permission from [257]. © 2019 Elsevier Ltd. All rights reserved

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Various biomaterials have been developed recently, that are capable of completely eradicating the bacterial growth and repairing the skin tissues at the wound site, rapidly. AuNPs-incorporated thermosensitive gels were developed by Arafa et al. for the transdermal delivery of AuNPs to act against S.aureus growth and heal burn-induced wounds. Two types of gels were developed; Type 1 contained only 15%w/w Pluronic® 127 (a polymer that is thermosensitive) along with AuNPs and Type 2 consisted of both Hypromellose (viscoelastic polymer) and Pluronic® 127 (15:1%w/w) in addition to AuNPs. From the ex-vivo, in-vivo, and in-vitro test results, Type 2 showed better bioadhesion, viscosity, and 100% drug release in 6 h while Type 1 had higher permeation flux and 98.03% release of drug in 6 h. Both Type 1 and 2 had better capability in acting against S.aureus and healing the wound and exhibited increased bioavailability when compared to that of the AuNPs in suspension form [248]. Another work using gold nanoparticles was done by Wang et al. in which, AuNPs of about 7 nm were combined with LL37 (Cathelicidin antimicrobial peptide) and vascular endothelial growth factor (VEGF), in order to develop a gene-delivery nanosystem for treating chronic diabetic wounds. The nanosystem showed notably higher capability in inserting the pDNA to keratinocytes, in the outermost layer of skin. It also exhibited high efficiency in antibacterial activity with lesser toxicity levels, endorsed angiogenesis, and thus helped in increasing the rate of closure of the wound [249].

Rangasamy et al. developed a special kind of AgNPs that were conjugated with Pyridoxine, having antibacterial characteristics, moisturizing properties, and properties for healing a wound. It was found that the synthesized nanoparticles were able to fasten the movement of keratinocytes and fibroblasts which supported the therapeutic effect on the wound [250]. Aloe vera is a plant that contains vitamins and amino acids abundantly. It is one of the perpetual elements used in cosmetics and medicines, which also has a soothing effect. These properties of aloe vera were made use by Chabala et al. and combined with the healing and antibacterial characteristics of AgNPs, chitosan-alginate polymer system, for develo** a new kind of dressing material for wounds. The polymer matrix with AgNPs, synthesized by the method of blending, was highly porous, which facilitated higher absorption and release of Aloe vera. The matrix in which Aloe vera and AgNPs are incorporated showed antibacterial property towards P.aeruginosa and S.aureus. This material can be used for wound healing applications in order to reduce the consequences of using antibiotics [251]. Tarusha et al. also developed a blended polymeric membrane consisting of hyaluronic acid, polysaccharides alginate, and Chitlac coated AgNPs, where Ca2+ ions were used as an agent for the cross-linking process, for healing chronic wounds. The matrix developed was highly efficient in eradicating and preventing the growth of the biofilms formed by bacteria and planktonic bacteria, and was proven to be non-cytotoxic to normal cell lines, due to the slow-release rate of Ag. The presence of Chitlac coated AgNPs helped in inhibiting the overexpression of proteolysis by Matrix metalloproteinases, which could hinder the wound healing process. The developed membrane possessed a better value of transmission rate of water vapours, which confirmed the presence of moisture on the wound bed, which would not allow any risk of dehydration and helps in the restoration of the tissues [252]. Oryan et al. synthesized AgNPs that were capped with chitosan in a single step and analyzed the outcomes when they were introduced to wounds caused by burns. After 7 days of application of the chitosan-capped AgNPs to the wound, a considerably low inflammation, an increase in the TGF-β1 and bFGF, improved and faster restoration of epithelial cells, and enhanced maturing of granulation tissue was noted. Therefore, it was evident that the chitosan-capped AgNPs were effective and highly encouraged faster healing of wounds caused by burns, by reducing the time taken by each repairing phase [253].

There are some cases where the delivered drugs are ineffective in killing the bacteria at the wound site since they resist the entry of drugs. AgNPs along with the photothermal therapy is being utilized in such situations, but the less effectiveness of the photothermal therapy and the toxicity caused because of the exposure of humans to high volumes of silver, are some of the limitations encountered during the application. To enhance the efficacy of the antibacterial agents, Liu et al. developed a nanocarrier by combining two different bactericidal agents into a single platform. Gold nanorods coated with polydopamine were loaded with Ag+ ions and Glycol chitosan which was labelled with Cyanine 5-SE. The developed therapeutic nanoplatform had a higher capacity in loading the Ag+ ions, and very low-dose release of Ag+ was pH-dependent which led to a selective agglomeration of Ag+ ions at the bacterial site. The low dosages of Ag+ ions were able to pierce through the membrane of the bacteria and were successfully able to moderate the resistance of the cell membrane posed towards heat, which later on led to the enhancement in the efficacy of photothermal therapy. Also, due to the hyperthermia caused, increased Ag+ release was observed, and thus development in the efficiency in killing the bacterial growth. These mechanisms were highly supportive of rapid wound healing and faster recovery from bacterial infection [254]. Chhibber et al. studied the efficiency of a microemulsion made from AgNPs that were coated with an alpha-amino acid, histidine, in healing infections caused by K.pneumoniae at the burn-wound site. There was a significant decrement in bacterial growth and the healing efficiency was improved. The developed microemulsion can be utilized for delivering therapeutics to those sites, where the bacteria which resist the antibiotics are present [255]. Altinbasak et al. developed a stable, nano polymeric mat that releases the antibiotic drugs to the affected area as and when irradiated with NIR radiation, by electrospinning PAA and rGO (Fig. 6B(a)). The mat synthesized displayed precise heating when irradiated with a 980 nm laser. When the antibiotic-loaded mat was exposed to the NIR laser, the rate of release of the drug was enhanced when compared to the rate of release in the absence of the NIR, and the rate was dependent on the power of the laser used. So, the amount of drug released can be controlled externally, based on the required quantity of antibiotics to kill the bacteria (Figs. 6B(b–e)) [256].

Ali et al. explored the capability of rGO in acting against the biofilms, which resist the entry of antibiotics to the wound site and promote chronic wounds. rGO along with C8H15NaO8 (carboxymethylcellulose sodium) formed a hydrogel and was confirmed that the hydrogel was efficient in restraining the growth of biofilms formed by P. aeruginosa and S. aureus, through the XTT test [258]. Fazli et al. developed a nanofiber-based mat using Chitosan and PEG, onto which Imipenem/Cilastatin-Hydrocortisone-coated ZnO nanoparticles were loaded. The swelling behaviour of the mat was at its maximum in the acidic environment and even after the complete utilization of the drug-loaded mat in buffer solution for a period of 8 days, its antibacterial property was conserved. The rate of release of Imipenem/Cilastatin (reduces infection) was found to be very slow when compared to that of the Hydrocortisone (inhibition of swelling) from the mat, which was appropriate for the wound healing dressings [259]. Gong et al. developed a biofilm from Chitosan, Alginate, and ZnO nanoparticles for managing wound dehiscence, which is quite common in patients who have received sutures in abdominopelvic surgeries. Alginate and chitosan are biodegradable polymers that are well known for their biocompatibility and the incorporated ZnO nanoparticles were observed to have a smaller size and large surface area, which highly influences its antimicrobial activity and its role in wound healing (Fig. 6C(a) (i, ii)). From the images taken after Masson’s trichrome staining, it was seen that the newly formed tissue wall in the wound site in the abdomen, exhibited high mechanical strength with increased deposition of collagen (Figs. 6C(b) (i–x)) [257]. Another work using ZnO nanoparticles was done by Masud et al., for enhanced healing of wounds through the controlled release of antibiotics. ZnO nanoparticles, Chitosan, and PEG were combined and linked through sodium triphosphate, and Gentamicin was loaded (loading efficiency-76%) onto the semi-porous nanocomposite. Because of the combinational effect of ZnO and gentamicin, the nanocomposite displayed increased bactericidal activity towards S.enterica and E.coli, when analyzed in-vitro. The prepared nanocomposite could be used as an effective wound dressing material since it degraded slowly in both PBS and water, offered moisture at the wound area, and exhibited enhanced healing characteristics by not leaving scars when compared to that of the commercially available hydrogels [260]. Even in the current times, curing an injury without leaving any scars is considered a big challenge due to some complications. Curcumin is well-known for its anti-inflammatory properties in healing any kind of wound. Bhattacharya et al. combined the anti-oxidant properties of nanoceria and the anti-inflammatory properties of Curcumin in order to find whether they could completely heal a wound without leaving scars. A hydrogel scaffold consisting of CeO2 NPs, PAA, and Curcumin was developed for dressing an acute wound. The release of Curcumin from the hydrogel was sustained and the efficiency in healing the wound was around 78%. The scaffold was applied only for one time and in a period of 7 days, the presence of renewed follicles of hair and an insignificant scar was found in comparison to that of the dressing material with Curcumin alone [261].

Xu et al. reported a study done on the efficacy of HAp incorporated with AuNPs and coated with polydopamine, in killing bacteria like S.aureus and E.coli, and healing the wound when combined with photothermal therapy. The free radicals (•OH) produced by the synthesized nanoparticles, make the bacteria susceptible to the change in temperature. At low and regulated temperature (45 °C), the nanoparticulate system was able to kill 95.2% of S.aureus and 96.8% of E.coli, and initiated skin-tissue regeneration. So, at a lower temperature, the bacteria were killed in a short period with high efficiency without affecting the normal skin tissue [262]. Similarly, Suja et al. prepared Fe-doped HAp as an antibacterial agent for various biomedical applications. Varying concentrations of Fe-do** was carried out in which the 0.2 M Fe doped HAp exhibited prominent antibacterial efficacy [263]. In another attempt by Suja et al., self-luminescent Mg doped HAp was prepared for the roles of antibacterial agent and drug carrier. The analyses were carried out on both the as-prepared as well as microwave irradiated nanoparticles. The microwave irradiated samples exhibited a sustained, quasi-Fickian drug release pattern and thus were found to be ideal for drug delivery applications [264].

4 Fate of inorganic nanoparticles post-application

The inherent physical as well as chemical characteristics of the inorganic nanoparticles, and the properties that evolve from these characteristics (such as quantum confinement and superparamagnetic behaviour) could moderately or completely vary as the particles interact with the physiological microenvironment [265]. For instance, a surface modified nanoparticle system when in contact with the physiological environment, could partially lose its coating, which could ultimately lead to instability of the particle system and their aggregation. As the nanoparticles are taken up by the cells, the protein layer protecting them will be enzymatically digested in the phagosomes or lysosomes. After the digestive process in the cell, the degraded nanoparticle system would be considered foreign and this triggers various immune responses inside the host. These degraded particles could initiate certain variations in the physicochemical characteristics of the residue [266]. These variations, like agglomeration of nanoparticles, could alter their biodistribution and also their immunogenicity. Thus, a precise and comprehensive investigation on such variations is prerequisite to clinical trials, especially in the case of inorganic nanoparticles.

5 Clinical trials and FDA-approval of inorganic nanoparticles

In the past two decades, the clinical trials and FDA and/or EMA approvals of inorganic nanoparticle-based drug carriers have sky-rocketed. On the basis of 2022 data, more than 100 nanoparticle-based formulations are available in the market [267, 268]. Due to the superparamagnetic behaviour of SPIONs, dextran coated SPION-based FDA approved imaging agents (Feridex®/ Endorem®) are readily available in the market. AuNPs are also one among the few inorganic nanoparticles that are FDA approved. Most of the AuNP-based clinical trials are carried out for applications such as contrast agents, drug delivery and photothermal therapy [269, 270]. Till date, the most accounted FDA approved inorganic nanoparticle is AgNPs, for many of its properties. AgNPs have attained greater commercialization, conquering 57% of the whole commercial products available. Few examples for the biocomposite wound dressing with AgNPs, with the US-FDA approval, are PolyMem Silver™ (Aspen), Aquacel™ (ConvaTec) and Tegaderm™ (3 M) [271]. Thus, conclusively, it is essential to focus on the efficiency as well as safety of the nanoparticles, whilst abiding by the regulations instituted by the agencies like EMA and FDA.

6 Outlook

The unification of nanoscience and nanotechnology with biomedicine has opened wide and stimulating paths for research, and some recent developments have indicated the greater potential of the nanoparticles for their applications in drug delivery. This review article has conversed about the physical, chemical, and biological properties of different inorganic nanoparticles, how these properties vary depending on the structure, shape, and size of the nanoparticle considered and has also outlined the exceptional properties of the inorganic nanoparticles which make them useful for designing ideal drug delivery systems. Furthermore, recent research developments in designing drug carriers using AuNPs, AgNPs, graphene-based nanoparticles, Iron oxide NPs, ZnO NPs, CeO2 NPs and nano HAp for different drug delivery applications have also been mentioned. Nevertheless, the authenticity of the inorganic particles, when compared to the organic nanoparticles, has been disputed as they are associated with certain restraining factors, which cause souring pain in the biomedical field.

In order to select the ideal nanoparticle for a drug delivery application, it is necessary to consider its factors like biocompatibility, drug-loading capacity, release kinetics, and targeting capabilities. Moreover, a thorough evaluation of the regulatory and safety aspects of nanoparticles in medical applications should be carried out. Extensive studies are being conducted by the researchers recently for determining the most appropriate nanoparticle for a specific therapeutic purpose.

The selection of nanoparticles for certain drug delivery applications also depends on various other factors like the specific drug being delivered, the proposed target, and the anticipated drug release kinetics. i.e., if targeting cancer cells is crucial, then AuNPs or graphene-based nanoparticles might be suitable due to their targeting capabilities. If antimicrobial properties are the prime concern, AgNPs could be considered. Iron oxide nanoparticles are useful whenever magnetic targeting is needed, and ZnO NPs can be utilized for wound healing. Thus, each of the nanoparticles mentioned in this article has unique properties that can make them suitable for drug delivery applications in different contexts.

The development of efficient nanoparticles, capable of delivering multiple drugs or therapeutic agents simultaneously, will gain prominence. This approach can significantly enhance the treatment efficacy and reduce the extent of resistance. Nanoparticles that respond to specific external stimuli, such as pH, light and/or temperature, will be highly explored. These "smart" nanoparticles can release drugs in response to the microenvironment of the target site, suggestively minimizing the systemic side effects. Develo** patient-specific drug delivery systems tailored to an individual's disease profile and genetic makeup, would be an exciting avenue to explore. As the nanoparticles advance towards the clinical applications, regulatory agencies will need to establish guidelines and safety standards that are specific to the nanoparticle-based drug vehicles.

Research in this area will involve meeting regulatory requirements and ensuring the product quality as well as safety. Develo** cost-effective, scalable production methods for the nanoparticles will be vital for their widespread adoption in the pharmaceutical arena. Transitioning the nanoparticle-based drug carriers from the laboratories to clinical trials and, eventually, to the market will be of significant focus. Researchers will need to address the clinical challenges, such as pharmacokinetics and the compliance by the patients. These research perspectives demonstrate a broader potential of utilization of nanoparticles as drug carriers and highlight the ongoing efforts to advance this field for better and improved healthcare outcomes. A collaborative effort between scientists, clinicians, regulatory bodies, and industrialists would be essential in driving these innovations toward clinical practice.