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Development, Optimization and In Vitro Characterization of Eudragit-Ganciclovir Nanosuspension or Treating Herpes Simplex Keratitis

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Abstract

Purpose

In the present study, we aimed to optimize, formulate and characterize Eudragit-based nanosuspension of Ganciclovir (GCV-NPs) as a carrier for ocular delivery. GCV is having a potential role in the treatment of herpes simplex keratitis caused by herpes simplex virus (HSV). The topical delivery of GCV is valuable for treating the HSK but it is limited due to its hydrophilic character. Hence, the purpose of the work was to develop nanosuspension of GCV with the help of a hydrophobic polymer Eudragit RL 100 in order to enhance the corneal permeation and to achieve sustained release of medication.

Methods

The GCV-NPs was formulated using nanoprecipitation method and the formula was optimized using central composite design. The optimized formulation was characterized for particle size (PS), zeta potential (ZP), entrapment efficiency (EE), polydispersity index (PDI), scanning electron microscopy (SEM), pH, in vitro drug release study and ex vivo transcorneal permeation study.

Results

The GCV-NPs were successfully developed using nanoprecipitation method. The optimized GCV-NPs have an average particle size of 260.8 ± 2.05 nm and drug entrapment efficiency of 51.06 ± 0.36%. The ZP and PDI were found to be − 10 ± 6.45 and 0.158 ± 0.02 respectively. The SEM images revealed a spherical shape for the optimized nanoparticles. The formulation has a pH of 6.96 ± 0.20. When compared with GCV solution, the optimized GCV-NPs exhibited a sustained release pattern and enhanced corneal permeation.

Conclusion

The formulated GCV-NPs have demonstrated several advantages like suitable pH, enhanced permeation and sustained release of medication. These findings indicate the potential role of GCV-NPs in ocular drug delivery.

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Data Availability

All data generated or analysed during this study are included in this article.

References

  1. Achouri D, Alhanout K, Piccerelle P, Andrieu V. Recent advances in ocular drug delivery. Dev Ind Pharm. 2013;39(11):1599–617.

    Article  CAS  Google Scholar 

  2. Sultana Y, Jain R, Aqil M, Ali A. Review of ocular drug delivery. Curr Drug deliv. 2006;3(2):207–17.

    Article  CAS  PubMed  Google Scholar 

  3. Lynch C, Kondiah PPD, Choonara YE, du Toit LC, Ally N, Pillay V. Advances in Biodegradable Nano-Sized polymer-based ocular drug delivery. Polymers (Basel). 2019;11(8):1371. https://doi.org/10.3390/polym11081371. PMID:31434273; PMCID:PMC6722735.

    Article  CAS  PubMed  Google Scholar 

  4. Vandervoort J, Annick L. Ocular drug delivery: nanomedicine applications. 2007:11–21.

  5. Singh S, Neelam SA, Singla YP. An overview of multifaceted significance of eudragit polymers in drug delivery systems. Asian J Pharm Clin Res. 2015;8(5):1–6.

    Article  Google Scholar 

  6. Pignatello R, Bucolo C, Puglisi G. Ocular tolerability of Eudragit RS100® and RL100® nanosuspensions as carriers for ophthalmic controlled drug delivery. J Pharm Sci. 2002;91(12):2636–41.

    Article  CAS  PubMed  Google Scholar 

  7. Taghe S, Mirzaeei S, Alany RG, Nokhodchi A. Polymeric inserts containing Eudragit® L100 nanoparticle for improved ocular delivery of azithromycin. Biomedicines. 2020;8(11):466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Akhter S, Talegaonkar S, Khan ZI, Jain GK, Khar RK, Ahmad FJ. Assessment of ocular pharmacokinetics and safety of Ganciclovir loaded nanoformulations. J Biomed Nanotech. 2011;7(1):144–5.

    Article  CAS  Google Scholar 

  9. Faulds D, Heel RC. Ganciclovir. A review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy in cytomegalovirus infections. Drugs. 1990;39(4):597–638.  https://doi.org/10.2165/00003495-199039040-00008. PMID: 2161731.

  10. Kapanigowda UG, Nagaraja SH, Ramaiah B, Boggarapu PR. Improved intraocular bioavailability of ganciclovir by mucoadhesive polymer based ocular microspheres: development and simulation process in Wistar rats. Daru. 2015;23:49. https://doi.org/10.1186/s40199-015-0132-7.PMID:26497653;PMCID:PMC4620023.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kaufman HE, Haw WH. Ganciclovir ophthalmic gel 0.15%: safety and efficacy of a new treatment for herpes simplex keratitis, Curr Eye Res. 2012;37:7654–660. https://doi.org/10.3109/02713683.2012.692846.

  12. Kumar N, Aggarwal R, Chauhan MK. Extended levobunolol release from Eudragit nanoparticle-laden contact lenses for glaucoma therapy. Futur J Pharm Sci. 2020;6:109. https://doi.org/10.1186/s43094-020-00128-9.

    Article  Google Scholar 

  13. Maaz A, Abdelwahed W, Tekko IA, Trefi S. Influence of nanoprecipitation method parameters on nanoparticles loaded with gatifloxacin for ocular drug delivery. 2015.

  14. Eid HM, Naguib IA, Alsantali RI, Alsalahat I, Hegazy AM. Novel chitosan-coated niosomal formulation for improved management of bacterial conjunctivitis: a highly permeable and efficient ocular nanocarrier for azithromycin. J Pharm Sci. 2021;110(8):3027–3036. ISSN 0022–3549. https://doi.org/10.1016/j.xphs.2021.04.020.

  15. Pujitha C, Jyothi JS, Sucharitha J, Lakshmi GN, Rao AL. Formulation and characterization of ofloxacin opthalmic GEL.

  16. Costa P, Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123–33.

    Article  CAS  PubMed  Google Scholar 

  17. Eid HM, Elkomy MH, El Menshawe SF, et al. Development, optimization, and in vitro/in vivo characterization of enhanced lipid nanoparticles for ocular delivery of ofloxacin: the influence of pegylation and chitosan coating. AAPS PharmSciTech. 2019;20:183. https://doi.org/10.1208/s12249-019-1371-6.

    Article  CAS  PubMed  Google Scholar 

  18. Dave V, Paliwal S. A novel approach to formulation factor of aceclofenac eye drops efficiency evaluation based on physicochemical characteristics of in vitro and in vivo permeation. Saudi Pharm J. 2014;22(3):240–5. https://doi.org/10.1016/j.jsps.2013.03.001.

    Article  PubMed  Google Scholar 

  19. Cetin M, Atila A, Kadioglu Y. Formulation and in vitro characterization of Eudragit® L100 and Eudragit® L100-PLGA nanoparticles containing diclofenac sodium. AAPS PharmSciTech. 2010;11(3):1250–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Alhamhoom Y, Ravi G, Osmani RAM, Hani U, Prakash GM. Formulation, characterization, and evaluation of eudragit-coated saxagliptin nanoparticles using 3 factorial design modules. Molecules. 2022;27(21):7510. https://doi.org/10.3390/molecules27217510. PMID:36364338; PMCID:PMC9653823.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sharma UK, Verma A, Prajapati SK, Pandey HS, Pandey AC. In vitro, in vivo and pharmacokinetic assessment of amikacin sulphate laden polymeric nanoparticles meant for controlled ocular drug delivery. Appl Nanosci. 2015;5:143–55.

    Article  CAS  Google Scholar 

  22. Galindo-Rodriguez S, Allémann E, Fessi H, Doelker E. Physicochemical parameters associated with nanoparticle formation in the salting-out, emulsification-diffusion, and nanoprecipitation methods. Pharm Res. 2004;8:1428–39. https://doi.org/10.1023/b:pham.0000036917.75634.be. PMID: 15359578.

    Article  Google Scholar 

  23. Katara R, Sachdeva S, Majumdar DK. Design, characterization, and evaluation of aceclofenac-loaded Eudragit RS 100 nanoparticulate system for ocular delivery. Pharm Dev Technol. 2019;24(3):368–79.

    Article  CAS  PubMed  Google Scholar 

  24. Sakhare S, Shinde SD, Yadav AV, Shete AS. Studies on formulation and evaluation of Eudragit RS PO based nanoparticulate system of aceclofenac for ocular delivery. Indian J Pharm Educ Res. 2021;55(1):S87-99.

    Article  CAS  Google Scholar 

  25. Mohammadi G, Mirzaeei S, Taghe S, Mohammadi P. Preparation and evaluation of Eudragit® L100 nanoparticles loaded impregnated with KT tromethamine loaded PVA-HEC insertions for ophthalmic drug delivery. Adv Pharm Bull. 2019;9(4):593.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Verma P, Gupta RN, Jha AK, Pandey R. Development, in vitro and in vivo characterization of Eudragit RL 100 nanoparticles for improved ocular bioavailability of acetazolamide. Drug Deliv. 2013;20(7):269–76. https://doi.org/10.3109/10717544.2013.834417. PMID: 24044644.

    Article  CAS  PubMed  Google Scholar 

  27. Ahmed L, Atif R, Eldeen TS, Yahya I, Omara A, Eltayeb M. Study the using of nanoparticles as drug delivery system based on mathematical models for controlled release. Int J Eng Technol. 2019;8(5):52–6.

    Google Scholar 

  28. Qaddoumi MG, Gukasyan HJ, Davda J, Labhasetwar V, Kim KJ, Lee VH. Clathrin and caveolin-1 expression in primary pigmented rabbit conjunctival epithelial cells: role in PLGA nanoparticle endocytosis. Mol Vis. 2003;9:559–68. PMID: 14566223.

    CAS  PubMed  Google Scholar 

  29. Morsi N, Ghorab D, Refai H, Teba H. Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery. Int J Pharm. 2016;506(1–2):57–67. https://doi.org/10.1016/j.ijpharm.2016.04.021. PMID: 27091293.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the management, Principal of Nirmala College of Pharmacy, Muvattupuzha, for supporting and encouraging us to carry out this research work.

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Authors and Affiliations

  1. Department of Pharmaceutics, Nirmala College of Pharmacy, 686661, Muvattupuzha, Kerala, India

    Soniya Peter, Manju Maria Mathews, Fels Saju & Swapna Paul

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  1. Soniya Peter
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  2. Manju Maria Mathews
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  3. Fels Saju
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Soniya Peter and Swapna Paul and guided by Manju Maria Mathews. The experimental design was performed by Fels Saju. All authors read and approved the final manuscript.

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Correspondence to Soniya Peter or Manju Maria Mathews.

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Peter, S., Mathews, M.M., Saju, F. et al. Development, Optimization and In Vitro Characterization of Eudragit-Ganciclovir Nanosuspension or Treating Herpes Simplex Keratitis. J Pharm Innov 18, 1328–1337 (2023). https://doi.org/10.1007/s12247-023-09723-8

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