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Lipoplexes’ Structure, Preparation, and Role in Managing Different Diseases

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Abstract

Lipid-based vectors are becoming promising alternatives to traditional therapies over the last 2 decades specially for managing life-threatening diseases like cancer. Cationic lipids are the most prevalent non-viral vectors utilized in gene delivery. The increasing number of clinical trials about lipoplex-based gene therapy demonstrates their potential as well-established technology that can provide robust gene transfection. In this regard, this review will summarize this important point. These vectors however have a modest transfection efficiency. This limitation can be partly addressed by using functional lipids that provide a plethora of options for investigating nucleic acid-lipid interactions as well as in vitro and in vivo nucleic acid delivery for biomedical applications. Despite their lower gene transfer efficiency, lipid-based vectors such as lipoplexes have several advantages over viral ones: they are less toxic and immunogenic, can be targeted, and are simple to produce on a large scale. Researchers are actively investigating the parameters that are essential for an effective lipoplex delivery method. These include factors that influence the structure, stability, internalization, and transfection of the lipoplex. Thorough understanding of the design principles will enable synthesis of customized lipoplex formulations for life-saving therapy.

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References

  1. Vodovozova EL. Editorial for special issue: liposomal and lipid-based drug Delivery systems and vaccines. Pharmaceutics. 2024;16:238. https://doi.org/10.3390/pharmaceutics16020238.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Mandal S, Mallik S, Bhoumick A, Bhattacharya A, Sen P. Synthesis of amino acid-based cationic lipids and study of the role of the cationic head group for enhanced drug and nucleic acid delivery. ChemBioChem. 2024;25(6):e202300834.

  3. Vaidya S, Mohod A, Eedara AC, Andugulapati SB, Pabbaraja S. Synthesis and characterization of a New Cationic lipid: efficient siRNA delivery and anticancer activity of Survivin-siRNA lipoplexes for the treatment of lung and breast cancers. ChemMedChem. 2023;18:e202300097.

    Article  CAS  PubMed  Google Scholar 

  4. Gandek TB, van der Koog L, Nagelkerke A. A comparison of cellular uptake mechanisms, delivery efficacy, and intracellular fate between liposomes and extracellular vesicles. Adv Healthc Mater. 2023;12:2300319.

    Article  CAS  Google Scholar 

  5. Husteden C, Brito Barrera YA, Tegtmeyer S, Borges J, Giselbrecht J, Menzel M, et al. Lipoplex-Functionalized Thin‐Film Surface Coating based on Extracellular Matrix Components as local Gene Delivery System to control osteogenic stem cell differentiation. Adv Healthc Mater. 2023;12:2201978.

    Article  CAS  Google Scholar 

  6. Wu Y, Yu B, Jackson A, Zha W, Lee LJ, Wyslouzil BE. Coaxial Electrohydrodynamic spraying: a Novel one-step technique to prepare Oligodeoxynucleotide Encapsulated Lipoplex nanoparticles. Mol Pharm. 2009;6:1371–9. https://doi.org/10.1021/mp9000348.

    Article  CAS  PubMed  Google Scholar 

  7. Balbino TA, Serafin JM, Malfatti-Gasperini AA, de Oliveira CLP, Cavalcanti LP, de Jesus MB, et al. Microfluidic Assembly of pDNA/Cationic Liposome Lipoplexes with High pDNA Loading for Gene Delivery. Langmuir. 2016;32:1799–807. https://doi.org/10.1021/acs.langmuir.5b04177.

    Article  CAS  PubMed  Google Scholar 

  8. Monnery BD. Polycation-mediated transfection: mechanisms of internalization and intracellular trafficking. Biomacromolecules. 2021;22:4060–83.

    Article  CAS  PubMed  Google Scholar 

  9. Adil MM, Erdman ZS, Kokkoli E. Transfection mechanisms of polyplexes, lipoplexes, and stealth liposomes in α5β1 integrin bearing DLD-1 colorectal cancer cells. Langmuir. 2014;30:3802–10.

    Article  CAS  PubMed  Google Scholar 

  10. Resina S, Prevot P, Thierry AR. Physico-Chemical characteristics of lipoplexes Influence cell uptake mechanisms and transfection efficacy. PLoS ONE. 2009;4:e6058. https://doi.org/10.1371/journal.pone.0006058.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Khajeei A, Masoomzadeh S, Gholikhani T, Javadzadeh Y. The effect of PEGylation on drugs’ pharmacokinetic parameters; from absorption to excretion. Curr Drug Deliv. 2024;21(7):978–92.

    Article  CAS  PubMed  Google Scholar 

  12. Li J, Zhang R, Du Y, Liu G, Dong Y, Zheng M, et al. Osteophilic and dual-regulated Alendronate‐Gene lipoplexes for reversing bone loss. Small. 2023;19:2303456.

    Article  CAS  Google Scholar 

  13. Pereira S, Santos RS, Moreira L, Guimarães N, Gomes M, Zhang H, et al. Lipoplexes to deliver oligonucleotides in Gram-positive and Gram-negative Bacteria: towards treatment of blood infections. Pharmaceutics. 2021;13:989. https://doi.org/10.3390/pharmaceutics13070989.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Patil TS, Deshpande AS. Mannosylated nanocarriers mediated site-specific drug delivery for the treatment of cancer and other infectious diseases: a state of the art review. J Controlled Release. 2020;320:239–52.

    Article  CAS  Google Scholar 

  15. Chandra J, Molugulu N, Annadurai S, Wahab S, Karwasra R, Singh S, et al. Hyaluronic acid-functionalized lipoplexes and polyplexes as emerging nanocarriers for receptor-targeted cancer therapy. Environ Res. 2023;233:116506.

  16. Faghfuri E. Recent advances in personalized cancer immunotherapy with immune checkpoint inhibitors, T cells and vaccines. Personalized Med. 2024;21:45–57.

    Article  CAS  Google Scholar 

  17. Ganley M, Holz LE, Minnell JJ, de Menezes MN, Burn OK, Poa KCY, et al. mRNA vaccine against malaria tailored for liver-resident memory T cells. Nat Immunol. 2023;24:1487–98.

    Article  CAS  PubMed  Google Scholar 

  18. Song S, Liu Z, Guo L, Yao W, Liu H, Yang M, et al. Continuous and size-control synthesis of lipopolyplex nanoparticles enabled by controlled micromixing performance for mRNA delivery. J Flow Chem. 2024:1–18. https://doi.org/10.1007/s41981-024-00316-1.

  19. Fan N, Chen K, Zhu R, Zhang Z, Huang H, Qin S, et al. Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants. Sci Adv. 2022;8:eabq3500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Tse S-W, McKinney K, Walker W, Nguyen M, Iacovelli J, Small C, et al. mRNA-encoded, constitutively active STINGV155M is a potent genetic adjuvant of antigen-specific CD8 + T cell response. Mol Ther. 2021;29:2227–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Tockary TA, Abbasi S, Matsui-Masai M, Hayashi A, Yoshinaga N, Boonstra E et al. Comb-structured mRNA vaccine tethered with short double-stranded RNA adjuvants maximizes cellular immunity for cancer treatment. Proc Nat Acad Sci. 2023;120:e2214320120.

  22. Sternberg B, Sorgi FL, Huang L. New structures in complex formation between DNA and cationic liposomes visualized by freeze-fracture electron microscopy. FEBS Lett. 1994;356:361–6. https://doi.org/10.1016/0014-5793(94)01315-2.

    Article  CAS  PubMed  Google Scholar 

  23. Chan K, Wong FS, Pearson JA. Circadian rhythms and pancreas physiology: a review. Front Endocrinol (Lausanne). 2022;13:920261. https://doi.org/10.3389/fendo.2022.920261.

    Article  PubMed  Google Scholar 

  24. Sengupta S, Bhattacharya G, Shaw S, Hans M, Devadas S. Immunomodulation in autoimmune disorders. Immunomodulators and Human Health, Springer; 2022. pp. 303–27.

    Google Scholar 

  25. Francis JE, Skakic I, Majumdar D, Taki AC, Shukla R, Walduck A, et al. Solid lipid nanoparticles delivering a DNA vaccine encoding Helicobacter pylori Urease A Subunit: Immune analyses before and after a mouse model of infection. Int J Mol Sci. 2024;25:1076.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Pinto IS, Cordeiro RA, Faneca H. Polymer- and lipid-based gene delivery technology for CAR T cell therapy. J Controlled Release. 2023;353:196–215. https://doi.org/10.1016/j.jconrel.2022.11.038.

    Article  CAS  Google Scholar 

  27. Khare P, Edgecomb SX, Hamadani CM, Tanner EEL, Manickam S. Lipid nanoparticle-mediated drug delivery to the brain. Adv Drug Deliv Rev. 2023;197:114861. https://doi.org/10.1016/j.addr.2023.114861.

    Article  CAS  PubMed  Google Scholar 

  28. Marquez CA, Oh C-I, Ahn G, Shin W-R, Kim Y-H, Ahn J-Y. Synergistic vesicle-vector systems for targeted delivery. J Nanobiotechnol. 2024;22:6.

    Article  Google Scholar 

  29. Srivastav AK, Karpathak S, Rai MK, Kumar D, Misra DP, Agarwal V. Lipid based drug delivery systems for oral, transdermal and parenteral delivery: recent strategies for targeted delivery consistent with different clinical application. J Drug Deliv Sci Technol. 2023;85:104526.

  30. Zeng S, Chen Y, Zhou F, Zhang T, Fan X, Chrzanowski W, et al. Recent advances and prospects for lipid-based nanoparticles as drug carriers in the treatment of human retinal diseases. Adv Drug Deliv Rev. 2023;199:114965.

  31. Belhadj Z, Qie Y, Carney RP, Li Y, Nie G. Current advances in non-viral gene delivery systems: liposomes versus extracellular vesicles. BMEMat. 2023;1:e12018.

    Article  Google Scholar 

  32. Bolhassani A. Lipid-based delivery systems in development of genetic and subunit vaccines. Mol Biotechnol. 2023;65:669–98.

    Article  CAS  PubMed  Google Scholar 

  33. Chhikara N, Singh J, Sharma A, Sood A, Kumar A. Functionalized lipoplexes and polyplexes for cancer therapy. In: Barabadi H, Mostafavi E, Mustansar Hussai C (eds) Functionalized Nanomaterials for Cancer Research. Elsevier; 2024. pp. 145–66.

  34. Ramamoorth M, Narvekar A. Non viral vectors in gene therapy-an overview. J Clin Diagn Research JCDR. 2015;9:GE01.

    Google Scholar 

  35. Kim K-D, Lieberman PM. Viral remodeling of the 4D nucleome. Exp Mol Med. 2024;56:799–808.

  36. Wang C, Pan C, Yong H, Wang F, Bo T, Zhao Y, et al. Emerging non-viral vectors for gene delivery. J Nanobiotechnol. 2023;21:272.

    Article  Google Scholar 

  37. Casper J, Schenk SH, Parhizkar E, Detampel P, Dehshahri A, Huwyler J. Polyethylenimine (PEI) in gene therapy: current status and clinical applications. J Controlled Release. 2023;362:667–91.

    Article  CAS  Google Scholar 

  38. Jiménez Blanco JL, Ortega-Caballero F, Blanco-Fernández L, Carmona T, Marcelo G, Martínez-Negro M, et al. Trehalose-based Janus cyclooligosaccharides: the click synthesis and DNA-directed assembly into pH-sensitive transfectious nanoparticles. Chem Commun (Camb). 2016;52:10117–20. https://doi.org/10.1039/c6cc04791b.

    Article  PubMed  Google Scholar 

  39. O’Keeffe Ahern J, Lara-Sáez I, Zhou D, Murillas R, Bonafont J, Mencía Á, et al. Non-viral delivery of CRISPR-Cas9 complexes for targeted gene editing via a polymer delivery system. Gene Ther. 2022;29:157–70. https://doi.org/10.1038/s41434-021-00282-6.

    Article  CAS  PubMed  Google Scholar 

  40. Badwaik VD, Aicart E, Mond**ou YA, Johnson MA, Bowman VD, Thompson DH. Structure-property relationship for in vitro siRNA delivery performance of cationic 2-hydroxypropyl-β-cyclodextrin: PEG-PPG-PEG polyrotaxane vectors. Biomaterials. 2016;84:86–98. https://doi.org/10.1016/j.biomaterials.2015.11.032.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Koltover I, Salditt T, Rädler JO, Safinya CR. An inverted hexagonal phase of cationic liposome-DNA complexes related to DNA release and delivery. Science. 1998;281:78–81. https://doi.org/10.1126/science.281.5373.78.

    Article  CAS  PubMed  Google Scholar 

  42. Hu D, Fumoto S, Yoshikawa N, Peng J, Miyamoto H, Tanaka M, et al. Diffusion coefficient of cationic liposomes during lipoplex formation determines transfection efficiency in HepG2 cells. Int J Pharm. 2023;637:122881.

    Article  CAS  PubMed  Google Scholar 

  43. Hu Y, Jiang K, Wang D, Yao S, Lu L, Wang H, et al. Core-shell lipoplexes inducing active macropinocytosis promote intranasal delivery of c-Myc siRNA for treatment of glioblastoma. Acta Biomater. 2022;138:478–90. https://doi.org/10.1016/j.actbio.2021.10.042.

    Article  CAS  PubMed  Google Scholar 

  44. Simberg D, Weisman S, Talmon Y, Faerman A, Shoshani T, Barenholz Y. The role of organ vascularization and lipoplex-serum initial contact in intravenous murine lipofection. J Biol Chem. 2003;278:39858–65. https://doi.org/10.1074/jbc.M302232200.

    Article  CAS  PubMed  Google Scholar 

  45. Wheeler CJ, Felgner PL, Tsai YJ, Marshall J, Sukhu L, Doh SG, et al. A novel cationic lipid greatly enhances plasmid DNA delivery and expression in mouse lung. Proc Natl Acad Sci U S A. 1996;93:11454–9. https://doi.org/10.1073/pnas.93.21.11454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Morán MC, Alonso T, Lima FS, Vinardell MP, Miguel MG, Lindman B. Counter-ion effect on surfactant–DNA gel particles as controlled DNA delivery systems. Soft Matter. 2012;8:3200–11.

    Article  Google Scholar 

  47. Pozzi D, Marchini C, Cardarelli F, Amenitsch H, Garulli C, Bifone A, et al. Transfection efficiency boost of cholesterol-containing lipoplexes. Biochim Biophys Acta. 2012;1818:2335–43. https://doi.org/10.1016/j.bbamem.2012.05.017.

    Article  CAS  PubMed  Google Scholar 

  48. Akhter S, Berchel M, Jaffrès P-A, Midoux P, Pichon C. mRNA lipoplexes with Cationic and Ionizable α-Amino-lipophosphonates: membrane Fusion, transfection, mRNA translation and conformation. Pharmaceutics. 2022;14:581. https://doi.org/10.3390/pharmaceutics14030581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Zhou S, Kawakami S, Higuchi Y, Yamashita F, Hashida M. The involvement of NK cell activation following intranasal administration of CpG DNA lipoplex in the prevention of pulmonary metastasis and peritoneal dissemination in mice. Clin Exp Metastasis. 2012;29:63–70.

    Article  CAS  PubMed  Google Scholar 

  50. Brigham KL, Lane KB, Meyrick B, Stecenko AA, Strack S, Cannon DR, et al. Transfection of nasal mucosa with a normal alpha1-antitrypsin gene in alpha1-antitrypsin-deficient subjects: comparison with protein therapy. Hum Gene Ther. 2000;11:1023–32.

    Article  CAS  PubMed  Google Scholar 

  51. Porteous DJ, Dorin JR, McLachlan G, Davidson-Smith H, Davidson H, Stevenson BJ, et al. Evidence for safety and efficacy of DOTAP cationic liposome mediated CFTR gene transfer to the nasal epithelium of patients with cystic fibrosis. Gene Ther. 1997;4:210–8. https://doi.org/10.1038/sj.gt.3300390.

    Article  CAS  PubMed  Google Scholar 

  52. Kichler A, Zauner W, Ogris M, Wagner E. Influence of the DNA complexation medium on the transfection efficiency of lipospermine/DNA particles. Gene Ther. 1998;5:855–60. https://doi.org/10.1038/sj.gt.3300658.

    Article  CAS  PubMed  Google Scholar 

  53. Boomer JA, Thompson DH, Sullivan SM. Formation of plasmid-based transfection complexes with an acid-labile cationic lipid: characterization of in vitro and in vivo gene transfer. Pharm Res. 2002;19:1292–301. https://doi.org/10.1023/a:1020342523694.

    Article  CAS  PubMed  Google Scholar 

  54. Nabel GJ, Nabel EG, Yang ZY, Fox BA, Plautz GE, Gao X, et al. Direct gene transfer with DNA-liposome complexes in melanoma: expression, biologic activity, and lack of toxicity in humans. Proc Natl Acad Sci U S A. 1993;90:11307–11. https://doi.org/10.1073/pnas.90.23.11307.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. **ng X, null Yujiao Chang J, Hung M. Preclinical and clinical study of HER-2/neu-targeting cancer gene therapy. Adv Drug Deliv Rev. 1998;30:219–27. https://doi.org/10.1016/s0169-409x(97)00118-x.

    Article  CAS  PubMed  Google Scholar 

  56. Hui KM, Ang PT, Huang L, Tay SK. Phase I study of immunotherapy of cutaneous metastases of human carcinoma using allogeneic and xenogeneic MHC DNA-liposome complexes. Gene Ther. 1997;4:783–90. https://doi.org/10.1038/sj.gt.3300455.

    Article  CAS  PubMed  Google Scholar 

  57. Sorscher EJ, Logan JJ, Frizzell RA, Lyrene RK, Bebok Z, Dong JY, et al. Gene therapy for cystic fibrosis using cationic liposome mediated gene transfer: a phase I trial of safety and efficacy in the nasal airway. Hum Gene Ther. 1994;5:1259–77. https://doi.org/10.1089/hum.1994.5.10-1259.

    Article  CAS  PubMed  Google Scholar 

  58. Bramson JL, Bodner CA, Graham RW. Activation of host antitumoral responses by cationic lipid/DNA complexes. Cancer Gene Ther. 2000;7:353–9. https://doi.org/10.1038/sj.cgt.7700143.

    Article  CAS  PubMed  Google Scholar 

  59. Le Bihan O, Chèvre R, Mornet S, Garnier B, Pitard B, Lambert O. Probing the in vitro mechanism of action of cationic lipid/DNA lipoplexes at a nanometric scale. Nucleic Acids Res. 2011;39:1595–609. https://doi.org/10.1093/nar/gkq921.

    Article  CAS  PubMed  Google Scholar 

  60. Aa M, Is B. Self-assembled lipoplexes of short interfering RNA (siRNA) using spermine-based fatty acid Amide Guanidines: Effect on Gene silencing efficiency. Pharmaceutics 2011;3. https://doi.org/10.3390/pharmaceutics3030406.

  61. Meekel AA, Wagenaar A, Šmisterová J, Kroeze JE, Haadsma P, Bosgraaf B, et al. Synthesis of pyridinium amphiphiles used for transfection and some characteristics of amphiphile/DNA complex formation. Eur J Org Chem. 2000;2000:665–73.

    Article  Google Scholar 

  62. Hattori Y, Tang M, Torii S, Tomita K, Sagawa A, Inoue N, et al. Optimal combination of cationic lipid and phospholipid in cationic liposomes for gene knockdown in breast cancer cells and mouse lung using siRNA lipoplexes. Mol Med Rep. 2022;26:253. https://doi.org/10.3892/mmr.2022.12769.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Gonçalves E, Debs RJ, Heath TD. The effect of liposome size on the final lipid/DNA ratio of cationic lipoplexes. Biophys J. 2004;86:1554–63. https://doi.org/10.1016/S0006-3495(04)74223-X.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Hohokabe M, Higashi K, Yamada Y, Fujimoto T, Tokumoto T, Imamura H, et al. Modification of liposomes composed of a cationic lipid TMAG and an anionic lipid DSPG with a PEGylated lipid based on the investigation of lipid structures. Colloids Surf a. 2023;661:130891.

    Article  CAS  Google Scholar 

  65. Simberg D, Danino D, Talmon Y, Minsky A, Ferrari ME, Wheeler CJ, et al. Phase behavior, DNA ordering, and size instability of cationic lipoplexes: relevance to optimal transfection activity. J Biol Chem. 2001;276:47453–9.

    Article  CAS  PubMed  Google Scholar 

  66. Lewis JG, Lin K-Y, Kothavale A, Flanagan WM, Matteucci MD, DePrince RB, et al. A serum-resistant cytofectin for cellular delivery of antisense oligodeoxynucleotides and plasmid DNA. Proc Natl Acad Sci. 1996;93:3176–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Ruiz F, Clancy J, Perricone M, Bebok Z, Hong J, Cheng S, et al. A clinical inflammatory syndrome attributable to aerosolized lipid–DNA administration in cystic fibrosis. Hum Gene Ther. 2001;12:751–61.

    Article  CAS  PubMed  Google Scholar 

  68. Aleku M, Schulz P, Keil O, Santel A, Schaeper U, Dieckhoff B, et al. Atu027, a liposomal small interfering RNA formulation targeting protein kinase N3, inhibits cancer progression. Cancer Res. 2008;68:9788–98.

    Article  CAS  PubMed  Google Scholar 

  69. Du Z, Munye MM, Tagalakis AD, Manunta MD, Hart SL. The role of the helper lipid on the DNA transfection efficiency of lipopolyplex formulations. Sci Rep. 2014;4:1–6.

    Article  Google Scholar 

  70. Sun M, Dang UJ, Yuan Y, Psaras AM, Osipitan O, Brooks TA, et al. Optimization of DOTAP/chol Cationic lipid nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery. AAPS PharmSciTech. 2022;23:135. https://doi.org/10.1208/s12249-022-02294-w.

    Article  CAS  PubMed  Google Scholar 

  71. Mamidi S, Cinci M, Hasmann M, Fehring V, Kirschfink M. Lipoplex mediated silencing of membrane regulators (CD46, CD55 and CD59) enhances complement-dependent anti-tumor activity of trastuzumab and pertuzumab. Mol Oncol. 2013;7:580–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Rädler JO, Koltover I, Salditt T, Safinya CR. Structure of DNA-cationic liposome complexes: DNA intercalation in multilamellar membranes in distinct interhelical packing regimes. Science. 1997;275:810–4. https://doi.org/10.1126/science.275.5301.810.

    Article  PubMed  Google Scholar 

  73. Das S, Negi S. A novel strategy for partial purification of alkane hydroxylase from P. Chrysogenum SNP5 through reconstituting its native membrane into liposome. Sci Rep. 2024;14:3779.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. El-Zahaby SA, Abdelhady SA, Ali MA, Younis SE, Elnaggar YS. Limosomes versus hyalurolimosomes loaded with piperine for management of skin cancer. Int J Pharm. 2024;650:123730.

    Article  CAS  PubMed  Google Scholar 

  75. Almofti MR, Harashima H, Shinohara Y, Almofti A, Li W, Kiwada H. Lipoplex size determines lipofection efficiency with or without serum. Mol Membr Biol. 2003;20:35–43.

    Article  CAS  PubMed  Google Scholar 

  76. Bessodes M, Dhotel H, Mignet N. Lipids for nucleic acid delivery: Cationic or Neutral Lipoplexes, Synthesis, and particle formation. Methods Mol Biol. 2019;1943:123–39. https://doi.org/10.1007/978-1-4939-9092-4_8.

    Article  CAS  PubMed  Google Scholar 

  77. Hofland HE, Shephard L, Sullivan SM. Formation of stable cationic lipid/DNA complexes for gene transfer. Proc Natl Acad Sci U S A. 1996;93:7305–9. https://doi.org/10.1073/pnas.93.14.7305.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Gershon H, Ghirlando R, Guttman SB, Minsky A. Mode of formation and structural features of DNA-cationic liposome complexes used for transfection. Biochemistry. 1993;32:7143–51.

    Article  CAS  PubMed  Google Scholar 

  79. MacDonald RC, Ashley GW, Shida MM, Rakhmanova VA, Tarahovsky YS, Pantazatos DP, et al. Physical and biological properties of cationic triesters of phosphatidylcholine. Biophys J. 1999;77:2612–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Schmutz M, Durand D, Debin A, Palvadeau Y, Etienne A, Thierry AR. DNA packing in stable lipid complexes designed for gene transfer imitates DNA compaction in bacteriophage. Proc Natl Acad Sci U S A. 1999;96:12293–8. https://doi.org/10.1073/pnas.96.22.12293.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Williams-Fegredo T, Davies L, Knevelman C, Mitrophanous K, Miskin J, Rafiq QA. Development of Novel Lipoplex Formulation methodologies to improve large scale transient transfection for Lentiviral Vector manufacture. Mol Ther Methods Clin Dev. 2024;32(2):101260..

  82. Ponti F, Campolungo M, Melchiori C, Bono N, Candiani G. Cationic lipids for gene delivery: many players, one goal. Chem Phys Lipids. 2021;235:105032. https://doi.org/10.1016/j.chemphyslip.2020.105032.

    Article  CAS  PubMed  Google Scholar 

  83. Coppola S, Estrada LC, Digman MA, Pozzi D, Cardarelli F, Gratton E, et al. Intracellular trafficking of cationic liposome-DNA complexes in living cells. Soft Matter. 2012;8:7919–27. https://doi.org/10.1039/C2SM25532D.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Khalil IA, Kogure K, Futaki S, Harashima H. High density of octaarginine stimulates macropinocytosis leading to efficient intracellular trafficking for gene expression. J Biol Chem. 2006;281:3544–51. https://doi.org/10.1074/jbc.M503202200.

    Article  CAS  PubMed  Google Scholar 

  85. Rehman AU, Busignies V, Coelho Silva Ribeiro M, Almeida Lage N, Tchoreloff P, Escriou V, et al. Fate of Tableted Freeze-dried siRNA lipoplexes in gastrointestinal environment. Pharmaceutics. 2021;13:1807. https://doi.org/10.3390/pharmaceutics13111807.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kim J, Kim JY, Kim H, Kim E, Park S, Ryu K-H, et al. Increasing transfection efficiency of Lipoplexes by modulating complexation solution for transient gene expression. Int J Mol Sci. 2021;22:12344. https://doi.org/10.3390/ijms222212344.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, et al. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987;84:7413–7. https://doi.org/10.1073/pnas.84.21.7413.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Elsana H, Olusanya TOB, Carr-wilkinson J, Darby S, Faheem A, Elkordy AA. Evaluation of novel cationic gene based liposomes with cyclodextrin prepared by thin film hydration and microfluidic systems. Sci Rep. 2019;9:15120. https://doi.org/10.1038/s41598-019-51065-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ge X, Chen L, Zhao B, Yuan W. Rationale and application of PEGylated lipid-based system for Advanced Target delivery of siRNA. Front Pharmacol 2021;11:598175.

  90. Hoffmann M, Gerlach S, Hoffmann C, Richter N, Hersch N, Csiszár, A et al. PEGylation and folic-acid functionalization of cationic lipoplexes—improved nucleic acid transfer into cancer cells. Front Bioeng Biotechnol 2022;10:1066887.

  91. Hattori Y, Tamaki K, Sakasai S, Ozaki K-I, Onishi H. Effects of PEG anchors in PEGylated siRNA lipoplexes on in vitro gene–silencing effects and siRNA biodistribution in mice. Mol Med Rep. 2020;22:4183–96. https://doi.org/10.3892/mmr.2020.11525.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Siakotos AN, Rouser G. Isolation of highly purified human and bovine brain endothelial cells and nuclei and their phospholipid composition. Lipids. 1969;4:234–9. https://doi.org/10.1007/BF02532638.

    Article  CAS  PubMed  Google Scholar 

  93. Leventis R, Silvius JR. Interactions of mammalian cells with lipid dispersions containing novel metabolizable cationic amphiphiles. Biochim Biophys Acta. 1990;1023:124–32. https://doi.org/10.1016/0005-2736(90)90017-i.

    Article  CAS  PubMed  Google Scholar 

  94. Koynova R, MacDonald RC. Mixtures of cationic lipid O-ethylphosphatidylcholine with membrane lipids and DNA: phase diagrams. Biophys J. 2003;85:2449–65. https://doi.org/10.1016/S0006-3495(03)74668-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Barrán-Berdón AL, Muñoz-Úbeda M, Aicart-Ramos C, Pérez L, Infante M-R, Castro-Hartmann P, et al. Ribbon-type and cluster-type lipoplexes constituted by a chiral lysine based cationic gemini lipid and plasmid DNA. Soft Matter. 2012;8:7368–80.

    Article  Google Scholar 

  96. Gao X, Huang L. A novel cationic liposome reagent for efficient transfection of mammalian cells. Biochem Biophys Res Commun. 1991;179:280–5.

    Article  CAS  PubMed  Google Scholar 

  97. Harashima H, Shinohara Y, Kiwada H. Intracellular control of gene trafficking using liposomes as drug carriers. Eur J Pharm Sci. 2001;13:85–9. https://doi.org/10.1016/s0928-0987(00)00211-6.

    Article  CAS  PubMed  Google Scholar 

  98. Zelphati O, Szoka FC. Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci U S A. 1996;93:11493–8. https://doi.org/10.1073/pnas.93.21.11493.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Meisel JW, Gokel GW. A simplified direct lipid mixing Lipoplex Preparation: comparison of Liposomal-, Dimethylsulfoxide-, and ethanol-based methods. Sci Rep. 2016;6:27662. https://doi.org/10.1038/srep27662.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Gustafsson J, Arvidson G, Karlsson G, Almgren M. Complexes between cationic liposomes and DNA visualized by cryo-TEM. Biochim Biophys Acta. 1995;1235:305–12. https://doi.org/10.1016/0005-2736(95)80018-b.

    Article  PubMed  Google Scholar 

  101. Zuhorn IS, Kalicharan R, Hoekstra D. Lipoplex-mediated transfection of mammalian cells occurs through the cholesterol-dependent clathrin-mediated pathway of endocytosis. J Biol Chem. 2002;277:18021–8. https://doi.org/10.1074/jbc.M111257200.

    Article  CAS  PubMed  Google Scholar 

  102. Ulrich AS. Biophysical aspects of using liposomes as delivery vehicles. Biosci Rep. 2002;22:129–50. https://doi.org/10.1023/a:1020178304031.

    Article  CAS  PubMed  Google Scholar 

  103. Harvie P, Wong FM, Bally MB. Characterization of lipid DNA interactions. I. destabilization of bound lipids and DNA dissociation. Biophys J. 1998;75:1040–51. https://doi.org/10.1016/S0006-3495(98)77593-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Heidari Z, Arora JS, Datta D, John VT, Kumar N, Bansal GP. Impact of the charge ratio on the in vivo immunogenicity of Lipoplexes. Pharm Res. 2017;34:1796–804. https://doi.org/10.1007/s11095-017-2187-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Khatri N, Baradia D, Vhora I, Rathi M, Misra A. Development and characterization of siRNA lipoplexes: Effect of different lipids, in Vitro evaluation in cancerous cell lines and in vivo toxicity study. AAPS PharmSciTech. 2014;15:1630–43. https://doi.org/10.1208/s12249-014-0193-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Kubota K, Onishi K, Sawaki K, Li T, Mitsuoka K, Sato T, et al. Effect of the nanoformulation of siRNA-lipid assemblies on their cellular uptake and immune stimulation. Int J Nanomed. 2017;12:5121–33. https://doi.org/10.2147/IJN.S136426.

    Article  CAS  Google Scholar 

  107. Apsite G, Timofejeva I, Vezane A, Vigante B, Rucins M, Sobolev A, et al. Synthesis and comparative evaluation of Novel Cationic Amphiphile C12-Man-Q as an efficient DNA delivery Agent in Vitro. Molecules. 2018;23:1540. https://doi.org/10.3390/molecules23071540.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Wang J, Wang D, Du T-T, Yi W-J, Liu Q. Reducible amino acid based cationic lipids with a naphthalimide moiety as non-viral gene vehicles. J Chem Res. 2022;46:17475198221145850. https://doi.org/10.1177/17475198221145850.

    Article  CAS  Google Scholar 

  109. Wani AK, Prakash A, Sena S, Akhtar N, Singh R, Chopra C, et al. Unraveling Molecular signatures in Rare Bone tumors and navigating the Cancer Pathway landscapes for targeted therapeutics. Crit Rev Oncol/Hematol 2024;196:104291.

  110. Mastorakos P, da Silva AL, Chisholm J, Song E, Choi WK, Boyle MP, et al. Highly compacted biodegradable DNA nanoparticles capable of overcoming the mucus barrier for inhaled lung gene therapy. Proc Natl Acad Sci U S A. 2015;112:8720–5. https://doi.org/10.1073/pnas.1502281112.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Olmsted SS, Padgett JL, Yudin AI, Whaley KJ, Moench TR, Cone RA. Diffusion of macromolecules and virus-like particles in human cervical mucus. Biophys J. 2001;81:1930–7. https://doi.org/10.1016/S0006-3495(01)75844-4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Tranchant I, Thompson B, Nicolazzi C, Mignet N, Scherman D. Physicochemical optimisation of plasmid delivery by cationic lipids. J Gene Med. 2004;6(Suppl 1):S24–35. https://doi.org/10.1002/jgm.509.

    Article  CAS  PubMed  Google Scholar 

  113. Li S, Huang L. In vivo gene transfer via intravenous administration of cationic lipid-protamine-DNA (LPD) complexes. Gene Ther. 1997;4:891–900. https://doi.org/10.1038/sj.gt.3300482.

    Article  CAS  PubMed  Google Scholar 

  114. Thierry AR, Rabinovich P, Peng B, Mahan LC, Bryant JL, Gallo RC. Characterization of liposome-mediated gene delivery: expression, stability and pharmacokinetics of plasmid DNA. Gene Ther. 1997;4:226–37. https://doi.org/10.1038/sj.gt.3300350.

    Article  CAS  PubMed  Google Scholar 

  115. Shi J, Yan W-W, Qi X-R, Yang L, Zhang L. Biodistribution and hepatocytes targeting of cationic liposomes surface-modified with sterylglucoside and golyethylene glycol. Yao Xue Xue Bao = Acta Pharm Sinica. 2004;39:551–5.

    CAS  Google Scholar 

  116. Filipczak N, Pan J, Yalamarty SSK, Torchilin VP. Recent advancements in liposome technology. Adv Drug Deliv Rev. 2020;156:4–22.

    Article  CAS  PubMed  Google Scholar 

  117. Lechardeur D, Sohn K, Haardt M, Joshi P, Monck M, Graham R, et al. Metabolic instability of plasmid DNA in the cytosol: a potential barrier to gene transfer. Gene Ther. 1999;6:482–97.

    Article  CAS  PubMed  Google Scholar 

  118. Boukhnikachvili T, Aguerre-Chariol O, Airiau M, Lesieur S, Ollivon M, Vacus J. Structure of in-serum transfecting DNA-cationic lipid complexes. FEBS Lett. 1997;409:188–94. https://doi.org/10.1016/s0014-5793(97)00505-x.

    Article  CAS  PubMed  Google Scholar 

  119. Plank C, Mechtler K, Szoka FC, Wagner E. Activation of the complement system by synthetic DNA complexes: a potential barrier for intravenous gene delivery. Hum Gene Ther. 1996;7:1437–46. https://doi.org/10.1089/hum.1996.7.12-1437.

    Article  CAS  PubMed  Google Scholar 

  120. Zhu N, Liggitt D, Liu Y, Debs R. Systemic gene expression after intravenous DNA delivery into adult mice. Science. 1993;261:209–11. https://doi.org/10.1126/science.7687073.

    Article  CAS  PubMed  Google Scholar 

  121. Lebrón JA, López-López M, García-Calderón CB, Rosado V, Balestra I, Huertas FR. Multivalent calixarene-based liposomes as platforms for Gene and Drug Delivery. Pharmaceutics. 2021;13:1250. https://doi.org/10.3390/pharmaceutics13081250.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Behr JP, Demeneix B, Loeffler JP, Perez-Mutul J. Efficient gene transfer into mammalian primary endocrine cells with lipopolyamine-coated DNA. Proc Natl Acad Sci U S A. 1989;86:6982–6. https://doi.org/10.1073/pnas.86.18.6982.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Broos K, Van der Jeught K, Puttemans J, Goyvaerts C, Heirman C, Dewitte H, et al. Particle-mediated intravenous delivery of antigen mRNA results in strong antigen-specific T-cell responses despite the induction of type I interferon. Mol Ther Nucleic Acids 2016;5(6):e326.

  124. Kranz LM, Diken M, Haas H, Kreiter S, Loquai C, Reuter KC, et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. 2016;534:396–401.

    Article  PubMed  Google Scholar 

  125. Krienke C, Kolb L, Diken E, Streuber M, Kirchhoff S, Bukur T, et al. A noninflammatory mRNA vaccine for treatment of experimental autoimmune encephalomyelitis. Science. 2021;371:145–53.

    Article  CAS  PubMed  Google Scholar 

  126. Farhood H, Serbina N, Huang L. The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. Biochim Biophys Acta. 1995;1235:289–95. https://doi.org/10.1016/0005-2736(95)80016-9.

    Article  PubMed  Google Scholar 

  127. Behr JP. Gene transfer with synthetic cationic amphiphiles: prospects for gene therapy. Bioconjug Chem. 1994;5:382–9. https://doi.org/10.1021/bc00029a002.

    Article  CAS  PubMed  Google Scholar 

  128. Alves RF, Favaro MT, Balbino TA, de Toledo MA, de la Torre LG, Azzoni AR. Recombinant protein-based nanocarriers and their association with cationic liposomes: characterization and in vitro evaluation. Colloids Surf A. 2017;513:1–10.

    Article  CAS  Google Scholar 

  129. Farhood H, Gao X, Son K, Yang YY, Lazo JS, Huang L, et al. Cationic liposomes for direct gene transfer in therapy of cancer and other diseases. Ann N Y Acad Sci. 1994;716:23–34. https://doi.org/10.1111/j.1749-6632.1994.tb21701.x. discussion 34–35.

    Article  CAS  PubMed  Google Scholar 

  130. López A, López-Cornejo P, López-López M, Lebrón JA, Ostos FJ, Pérez-Alfonso D, et al. Influence of the degree of oligomerization of surfactants on the DNA/surfactant interaction. Colloids Surf B Biointerfaces. 2019;182:110399. https://doi.org/10.1016/j.colsurfb.2019.110399.

    Article  CAS  PubMed  Google Scholar 

  131. Yadav BK, Khursheed A, Singh RD, Cocrystals. A complete review on conventional and novel methods of its formation and its evaluation. Asian J Pharm Clin Res. 2019;12:68–74.

    Article  CAS  Google Scholar 

  132. Kirkham M, Parton RG. Clathrin-independent endocytosis: new insights into caveolae and non-caveolar lipid raft carriers. Biochim et Biophys Acta (BBA)-Molecular Cell Res. 2005;1745:273–86.

    Article  CAS  Google Scholar 

  133. Kikuchi A, Aoki Y, Sugaya S, Serikawa T, Takakuwa K, Tanaka K, et al. Development of novel cationic liposomes for efficient gene transfer into peritoneal disseminated tumor. Hum Gene Ther. 1999;10:947–55. https://doi.org/10.1089/10430349950018346.

    Article  CAS  PubMed  Google Scholar 

  134. Sánchez-Arribas N, Martínez-Negro M, Villar EM, Pérez L, Osío Barcina J, Aicart E, et al. Protein expression knockdown in Cancer cells Induced by a Gemini Cationic lipid nanovector with histidine-based Polar heads. Pharmaceutics. 2020;12:791. https://doi.org/10.3390/pharmaceutics12090791.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Budker V, Gurevich V, Hagstrom JE, Bortzov F, Wolff JA. pH-sensitive, cationic liposomes: a new synthetic virus-like vector. Nat Biotechnol. 1996;14:760–4. https://doi.org/10.1038/nbt0696-760.

    Article  CAS  PubMed  Google Scholar 

  136. Maurer N, Mori A, Palmer L, Monck MA, Mok KW, Mui B, et al. Lipid-based systems for the intracellular delivery of genetic drugs. Mol Membr Biol. 1999;16:129–40. https://doi.org/10.1080/096876899294869.

    Article  CAS  PubMed  Google Scholar 

  137. Niu L, Xu Y-C, Dai Z, Tang H-Q. Gene therapy for type 1 diabetes mellitus in rats by gastrointestinal administration of chitosan nanoparticles containing human insulin gene. World J Gastroenterol. 2008;14:4209–15. https://doi.org/10.3748/wjg.14.4209.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Silva SG, Oliveira IS, do Vale MLC, Marques EF. Serine-based gemini surfactants with different spacer linkages: from self-assembly to DNA compaction. Soft Matter. 2014;10:9352–61. https://doi.org/10.1039/c4sm01771d.

    Article  CAS  PubMed  Google Scholar 

  139. Nascimento TL, Hillaireau H, Noiray M, Bourgaux C, Arpicco S, Pehau-Arnaudet G, et al. Supramolecular Organization and siRNA binding of Hyaluronic Acid-Coated lipoplexes for targeted delivery to the CD44 receptor. Langmuir. 2015;31:11186–94. https://doi.org/10.1021/acs.langmuir.5b01979.

    Article  CAS  PubMed  Google Scholar 

  140. Medaer L, Veys K, Gijsbers R. Current status and prospects of viral vector-based gene therapy to treat kidney diseases. Hum Gene Ther. 2024;35(5–6):139–50.

    Article  CAS  PubMed  Google Scholar 

  141. Yan J, Zhang H, Li G, Su J, Wei Y, Xu C. Lipid nanovehicles overcome barriers to systemic RNA delivery: lipid components, fabrication methods, and rational design. Acta Pharm Sinica B. 2024;14(2):579–601.

    Article  CAS  Google Scholar 

  142. Tavitian B, Marzabal S, Boutet V, Kühnast B, Terrazzino S, Moynier M, et al. Characterization of a synthetic anionic vector for oligonucleotide delivery using in vivo whole body dynamic imaging. Pharm Res. 2002;19:367–76. https://doi.org/10.1023/a:1015133205457.

    Article  CAS  PubMed  Google Scholar 

  143. Kim N, Yoo J, Atala A, Lee S. Small RNA delivery for in situ tissue regeneration. In: Lee SJ, Yoo JJ, Atala A (eds) In Situ Tissue Regeneration. Boston: Academic Press; 2016. pp. 111–35.

  144. Zhou F, Jia X, Yang Q, Yang Y, Zhao Y, Fan Y, et al. Targeted delivery of microRNA-126 to vascular endothelial cells via REDV peptide modified PEG-trimethyl chitosan. Biomaterials Sci. 2016;4:849–56.

    Article  CAS  Google Scholar 

  145. Caracciolo G, Amenitsch H. Cationic liposome/DNA complexes: from structure to interactions with cellular membranes. Eur Biophys J. 2012;41:815–29. https://doi.org/10.1007/s00249-012-0830-8.

    Article  CAS  PubMed  Google Scholar 

  146. Lv H, Zhang S, Wang B, Cui S, Yan J. Toxicity of cationic lipids and cationic polymers in gene delivery. J Controlled Release. 2006;114:100–9. https://doi.org/10.1016/j.jconrel.2006.04.014.

    Article  CAS  Google Scholar 

  147. Ranjbar S, Zhong X, Manautou J, Lu X. A holistic analysis of the intrinsic and delivery-mediated toxicity of siRNA therapeutics. Adv Drug Deliv Rev. 2023;201:115052. https://doi.org/10.1016/j.addr.2023.115052.

    Article  CAS  PubMed  Google Scholar 

  148. Ibrahim M, Ramadan E, Elsadek NE, Emam SE, Shimizu T, Ando H, et al. Polyethylene glycol (PEG): the nature, immunogenicity, and role in the hypersensitivity of PEGylated products. J Controlled Release. 2022;351:215–30. https://doi.org/10.1016/j.jconrel.2022.09.031.

    Article  CAS  Google Scholar 

  149. Stavnsbjerg C, Christensen E, Münter R, Henriksen JR, Fach M, Parhamifar L, et al. Accelerated blood clearance and hypersensitivity by PEGylated liposomes containing TLR agonists. J Controlled Release. 2022;342:337–44. https://doi.org/10.1016/j.jconrel.2021.12.033.

    Article  CAS  Google Scholar 

  150. Stepanenko AA, Heng HH. Transient and stable vector transfection: pitfalls, off-target effects, artifacts. Mutat Research/Reviews Mutat Res. 2017;773:91–103. https://doi.org/10.1016/j.mrrev.2017.05.002.

    Article  CAS  Google Scholar 

  151. Paramshetti S, Angolkar M, Talath S, Osmani RAM, Spandana A, Al Fatease A, et al. Unravelling the in vivo dynamics of liposomes: insights into biodistribution and cellular membrane interactions. Life Sci 2024;346:122616.

  152. Ko T, Fumoto S, Kurosaki T, Nakashima M, Miyamoto H, Sasaki H, et al. Interaction of γ-Polyglutamic Acid/Polyethyleneimine/Plasmid DNA ternary complexes with serum components plays a crucial role in Transfection in mice. Pharmaceutics. 2024;16:522. https://doi.org/10.3390/pharmaceutics16040522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Conceptualization: Sally A. El-Zahaby; Interpretation of data: Sally A. El-Zahaby, Lovepreet Kaur, Ankur Sharma, Aprameya Ganesh Prasad, Atif Khurshid Wani & Rattandeep Singh, Visualization: Sally A. El-Zahaby & Aprameya Ganesh Prasad; Writing - original draft: Sally A. El-Zahaby, Aprameya Ganesh Prasad & Atif Khurshid Wani; Writing–review & editing: Sally A. El-Zahaby, Lovepreet Kaur, Ankur Sharma, Aprameya Ganesh Prasad, Atif Khurshid Wani, Rattandeep Singh, Mohamed Y. Zakaria; Final approval of the version to be published: Sally A. El-Zahaby, Lovepreet Kaur, Ankur Sharma, Aprameya Ganesh Prasad, Atif Khurshid Wani, Rattandeep Singh, Mohamed Y. Zakaria.

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El-Zahaby, S.A., Kaur, L., Sharma, A. et al. Lipoplexes’ Structure, Preparation, and Role in Managing Different Diseases. AAPS PharmSciTech 25, 131 (2024). https://doi.org/10.1208/s12249-024-02850-6

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