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Development of Liposomal Formulation for Controlled Delivery of Valacyclovir: an In Vitro Study

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Abstract

Purpose

Herpes, a highly contagious viral infection caused by the herpes simplex virus, infects the face to any other body part of the skin, even the genital areas. Among the anti-herpes drugs, valacyclovir (VCV) possesses 55–70% oral bioavailability and more improved performance than acyclovir (15–20% oral bioavailability). However, a high daily intake of around 1 g is required. This work aimed to prepare a suitable carrier system to enhance bioavailability of VCV with reduced dose and dose-related side effects.

Methods

The processes of thin film hydration and reverse-phase evaporation were employed to synthesize liposomes encapsulating VCV, which were then subjected to basic characterizations such particle size and zeta potential. Moreover, FESEM and cryo-EM studies of the optimized formulation were also performed. FTIR spectroscopy was performed to detect incompatibility present if any between drug and excipients. The percentage drug loading and in vitro drug release were studied by UV–Visible spectrophotometer.

Results

The results showed that the liposome vesicles were in nanosize range (140 ± 4.1 nm) with good colloidal stability (−62.75 ± 3.18 mV; the zeta potential) with appreciable drug loading capability. In vitro drug release studies revealed a biphasic release pattern, with initial burst release lasting up to 2 h and then continuous drug release. About 73% drug was released after 48 h.

Conclusion

Based on the findings, it was determined that VCV, a widely used drug for the treatment and prevention of viral infections in humans, may be formulated as a liposome for the successful treatment of herpes with a lower dose and improved bioavailability.

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Data Availability

The datasets used or analysed during the current study are available from the corresponding author on reasonable request.

References

  1. World Health Organization. WHO guidelines for the treatment of genital herpes simplex virus. World Health Organization. 2016.

  2. Wagstaff AJ, Faulds D, Goa KL. Aciclovir. Drugs. 1994;47(1):153–205.

    Article  CAS  PubMed  Google Scholar 

  3. Granero GE, Amidon GL. Stability of valacyclovir: implications for its oral bioavailability. Int J Pharm. 2006;317(1):14–8.

    Article  CAS  PubMed  Google Scholar 

  4. Gilbert S, McBurney E. Use of valacyclovir for herpes simplex virus-1 (HSV-1) prophylaxis after facial resurfacing: a randomized clinical trial of dosing regimens. Dermatol Surg. 2000;26(1):50–4.

    Article  CAS  PubMed  Google Scholar 

  5. Cunha BA, Baron J. The pharmacokinetic basis of oral valacyclovir treatment of herpes simplex virus (HSV) or varicella zoster virus (VZV) meningitis, meningoencephalitis or encephalitis in adults. J Chemother. 2017;29(2):122–5.

    Article  PubMed  Google Scholar 

  6. Kumar R, Sinha V. Lipid nanocarrier: an efficient approach towards ocular delivery of hydrophilic drug (Valacyclovir). AAPS PharmSciTech. 2017;18(3):884–94.

    Article  CAS  PubMed  Google Scholar 

  7. Nair P, Gharote H, Singh P, Jain-Choudhary P. Herpes zoster on the face in the elderly. Case Rep 2014;bcr2013200101.

  8. Spruance SL, Nett R, Marbury T, Wolff R, Johnson J, Spaulding T. Acyclovir cream for treatment of herpes simplex labialis: results of two randomized, double-blind, vehicle-controlled, multicenter clinical trials. Antimicrob Agents Chemother. 2002;46(7):2238–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Pacheco-Quito E-M, Ruiz-Caro R, Rubio J, Tamayo A, Veiga M-D. Carrageenan-based acyclovir mucoadhesive vaginal tablets for prevention of genital herpes. Mar Drugs. 2020;18(5):249.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Mohammadi M, Elahimehr Z, Mahboobian MM. Acyclovir-loaded nanoemulsions: preparation, characterization and irritancy studies for ophthalmic delivery. Curr Eye Res. 2021;46(11):1646–52.

    Article  CAS  PubMed  Google Scholar 

  11. Pradhan B, Kumar N, Saha S, Roy A. Liposome: method of preparation, advantages, evaluation and its application. J Appli Pharm Res. 2015;3(3):01–8.

    Google Scholar 

  12. Amoabediny G, Haghiralsadat F, Naderinezhad S, Helder MN, Akhoundi Kharanaghi E, Mohammadnejad Arough J, Zandieh-Doulabi B. Overview of preparation methods of polymeric and lipid-based (niosome, solid lipid, liposome) nanoparticles: a comprehensive review. Int J Polym Mater Polym Biomater 2018;67(6):383–400.

  13. Ajeeshkumar KK, Aneesh PA, Raju N, Suseela M, Ravishankar CN, Benjakul S. Advancements in liposome technology: preparation techniques and applications in food, functional foods, and bioactive delivery: a review. Compr Rev Food Sci Food Saf. 2021;20(2):1280–306.

    Article  CAS  PubMed  Google Scholar 

  14. Sengupta S, Paul P, Mukherjee B, Gaonkar RH, Debnath MC, Chakraborty R, Khatun N, Roy S. Peripheral nerve targeting by procaine-conjugated ribavirin-loaded dual drug nanovesicle. Nanomedicine. 2018;13(23):3009–23.

    Article  CAS  PubMed  Google Scholar 

  15. Han B, Yang Y, Chen J, Tang H, Sun Y, Zhang Z, Wang Z, Li Y, Li Y, Luan X. Preparation, characterization, and pharmacokinetic study of a novel long-acting targeted paclitaxel liposome with antitumor activity. Int J Nanomed. 2020;15:553.

    Article  CAS  Google Scholar 

  16. Dutta L, Mukherjee B, Chakraborty T, Das MK, Mondal L, Bhattacharya S, Gaonkar RH, Debnath MC. Lipid-based nanocarrier efficiently delivers highly water soluble drug across the blood–brain barrier into brain. Drug Deliv. 2018;25(1):504–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Satapathy BS, Mukherjee B, Baishya R, Debnath MC, Dey NS, Maji R. Lipid nanocarrier-based transport of docetaxel across the blood brain barrier. RSC Adv. 2016;6(88):85261–74.

    Article  CAS  Google Scholar 

  18. Shekhar Dey N, Mukherjee B, Maji R, Sankar Satapathy B. Development of linker-conjugated nanosize lipid vesicles: a strategy for cell selective treatment in breast cancer. Curr Cancer Drug Targets 2016;16(4):357–72.

  19. Rudra A, Deepa RM, Ghosh MK, Ghosh S, Mukherjee B. Doxorubicin-loaded phosphatidylethanolamine-conjugated nanoliposomes: in vitro characterization and their accumulation in liver, kidneys, and lungs in rats. Int J Nanomed. 2010;5:811.

    CAS  Google Scholar 

  20. Paul P, Sengupta S, Mukherjee B, Shaw TK, Gaonkar RH, Debnath MC. Chitosan-coated nanoparticles enhanced lung pharmacokinetic profile of voriconazole upon pulmonary delivery in mice. Nanomedicine. 2018;13(5):501–20.

    Article  CAS  PubMed  Google Scholar 

  21. Douda J, Calderón LM, Kryshtab T, Cerón JA, Kryvko A. Synthesis and characterization of II–VI (CdSe) quantum dot encapsulated liposomes. J Mater Sci Mater Electron. 2018;29(18):15570–8.

    Article  CAS  Google Scholar 

  22. Weber F, Rahnfeld L, Luciani P. Analytical profiling and stability evaluation of liposomal drug delivery systems: a rapid UHPLC-CAD-based approach for phospholipids in research and quality control. Talanta. 2020;220: 121320.

    Article  CAS  PubMed  Google Scholar 

  23. Chauhan T, Rani V, Sahu B, Sharma A, Kheruka SC, Gambhir S, Dube V, Aggarwal LM, Chawla R. Negatively charged liposomes of sertraline hydrochloride: formulation, characterization and pharmacokinetic studies. J Drug Deliv Sci Technol. 2020;58:101780.

    Article  CAS  Google Scholar 

  24. Shaw TK, Mandal D, Dey G, Pal MM, Paul P, Chakraborty S, Ali KA, Mukherjee B, Bandyopadhyay AK, Mandal M. Successful delivery of docetaxel to rat brain using experimentally developed nanoliposome: a treatment strategy for brain tumor. Drug Deliv. 2017;24(1):346–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Cheng C, Wu Z, McClements DJ, Zou L, Peng S, Zhou W, Liu W. Improvement on stability, loading capacity and sustained release of rhamnolipids modified curcumin liposomes. Colloids Surf B. 2019;183:110460.

    Article  CAS  Google Scholar 

  26. Das S, Samanta A, Mondal S, Roy D, Nayak AK. Design and release kinetics of liposomes containing abiraterone acetate for treatment of prostate cancer. Sens Int. 2021;2:100077.

    Article  Google Scholar 

  27. Karami K, Jamshidian N, Hajiaghasi A, Amirghofran Z. BSA nanoparticles as controlled release carriers for isophethalaldoxime palladacycle complex; synthesis, characterization, in vitro evaluation, cytotoxicity and release kinetics analysis. New J Chem. 2020;44(11):4394–405.

    Article  CAS  Google Scholar 

  28. Ugwu S, Zhang A, Parmar M, Miller B, Sardone T, Peikov V, Ahmad I. Preparation, characterization, and stability of liposome-based formulations of mitoxantrone. Drug Dev Ind Pharm. 2005;31(2):223–9.

    Article  CAS  PubMed  Google Scholar 

  29. Singh VK, Pandey PM, Agarwal T, Kumar D, Banerjee I, Anis A, Pal K. Development of soy lecithin based novel self-assembled emulsion hydrogels. J Mech Behav Biomed Mater. 2016;55:250–63.

    Article  CAS  Google Scholar 

  30. Das PJ, Paul P, Mukherjee B, Mazumder B, Mondal L, Baishya R, Debnath MC, Dey KS. Pulmonary delivery of voriconazole loaded nanoparticles providing a prolonged drug level in lungs: a promise for treating fungal infection. Mol Pharm. 2015;12(8):2651–64.

    Article  CAS  PubMed  Google Scholar 

  31. Ghosh S, Mondal L, Chakraborty S, Mukherjee B. Early stage HIV management and reduction of stavudine-induced hepatotoxicity in rats by experimentally developed biodegradable nanoparticles. AAPS PharmSciTech. 2017;18(3):697–709.

    Article  CAS  PubMed  Google Scholar 

  32. Lombardo D, Kiselev MA. Methods of liposomes preparation: formation and control factors of versatile nanocarriers for biomedical and nanomedicine application. Pharmaceutics 2022;14(3).

  33. Akbari A, Akbarzadeh A, Rafiee Tehrani M, Cohan RA, Mozaffari A, Memarzadeh M. Preparation and evaluation of a liposome drug delivery system in cancer treatment in vitro. J Nanostruct. 2020;10(1):140–47.

  34. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A, Khorasani S, Mozafari M. Impact of particle size and polydispersity index on the clinical applications of lipidic nanocarrier systems. Pharmaceutics. 2018;10(2):57.

  35. Shahraki N, Mehrabian A, Amiri-Darban S, Moosavian SA, Jaafari MR. Preparation and characterization of PEGylated liposomal Doxorubicin targeted with leptin-derived peptide and evaluation of their anti-tumor effects, in vitro and in vivo in mice bearing C26 colon carcinoma. Colloids Surf B. 2021;200:111589.

    Article  CAS  Google Scholar 

  36. Oh N, Park J-H. Endocytosis and exocytosis of nanoparticles in mammalian cells. Int J Nanomed. 2014;9(Suppl 1):51.

    Google Scholar 

  37. Vu MT, Le NTT, Pham TLB, Nguyen NH, Nguyen DH. Development and characterization of soy lecithin liposome as potential drug carrier systems for codelivery of letrozole and paclitaxel. J Nanomater. 2020.

  38. Pattnaik G, Sinha B, Mukherjee B, Ghosh S, Basak S, Mondal S, Bera T. Submicron-size biodegradable polymer-based didanosine particles for treating HIV at early stage: an in vitro study. J Microencapsul. 2012;29(7):666–76.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors sincerely acknowledged Aurobindo Pharma Limited, Hyderabad, for gifting Valacyclovir HCl for conducting research. The authors sincerely acknowledge the University of North Bengal, India, for providing necessary support, facilities, and e-resources to conduct this work.

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Authors

Contributions

Conception, design of work, and supervision, P.P.; experimental execution, A.M., A.D., A.K.; analysis and interpretation of the data, G.N., R.S., T.K.S., T.K.D; drafting of the manuscript, A.M. and P.P.; revision of the manuscript, T.K.D., P.P., G.N., R.S., T.K.S.; funding acquisition, R.S. and G.N.

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Correspondence to Paramita Paul.

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Mallick, A., Sahu, R., Nandi, G. et al. Development of Liposomal Formulation for Controlled Delivery of Valacyclovir: an In Vitro Study. J Pharm Innov 18, 1020–1029 (2023). https://doi.org/10.1007/s12247-022-09706-1

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