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Development of brimonidine niosomes laden contact lenses for extended release and promising delivery system in glaucoma treatment

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Abstract

Background

Increased intraocular pressure is a common symptom of glaucoma. In severe circumstances, it may result in loss of eyesight. Glaucoma treatment is difficult due to ocular physiological barriers that prevent medications from reaching the afflicted area. Traditional formulations (eye drops) have a short residence period and are rapidly drained away via the nasolacrimal duct, resulting in increased adverse drug responses and lower efficacy. The usage of nanoparticles such as niosomes could be one potential answer to these problems. While niosomes improve drug penetration, they have little effect on ocular retention of the medication. Contact lenses containing niosomes can assist to overcome this disadvantage.

Objective

This study aims to prepare and evaluate Brimonidine niosomes laden contact lenses for the treatment of Glaucoma.

Methods

Brimonidine niosomes were prepared using thin film hydration method and evaluated. The contact lenses were soaked in the niosomal formulation at varying intervals (3–10 days). Thereafter, the contact lenses were evaluated for %transmittance, %swelling index, drug quantification and in vitro drug release. The pharmacodynamic studies were conducted to assess the reduction in intraocular pressure (IOP) in albino rabbits. The research compared the results of the reduction in intraocular pressure caused by Brimonidine niosomes laden contact lenses with a marketed preparation of niosomes.

Results

Higher concentration of the drug was loaded in contact lenses loaded with Brimonidine niosomes compared to the marketed formulation, by soaking method. The contact lenses exhibited an optimal %transmittance of 98.02 ± 0.36 and %swelling index of 50.35 ± 0.57. Increase in the soaking time up to 7 days led to an increase in the drug concentration in the contact lenses. However, no further increase was observed after the 7th day due to saturation of the contact lenses. Brimonidine niosomes laden contact lenses provided a reduction in intraocular pressure that was similar to the marketed preparation. Further, the contact lenses provided extended release up to 20 h.

Conclusion

Brimonidine niosomes laden contact lenses exhibited superior drug loading through the soaking method, displaying optimal %transmittance and %swelling index. Soaking for 7 days increased drug concentration in contact lenses with no further increase due to saturation. These lenses reduced intraocular pressure like the marketed formulation, offering extended release for 20 h.

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Data availability

The authors declare that the data supporting the findings of this study are available within the paper. Any other data required can be made available upon request to the authors.

References

  1. Yadav KS, Rajpurohit R, Sharma S. Glaucoma: current treatment and impact of advanced drug delivery systems. Life Sci. 2019;221:362–76. https://doi.org/10.1016/j.lfs.2019.02.029.

    Article  CAS  PubMed  Google Scholar 

  2. Yadav KS, Sharma S, Londhe VY. Bio-tactics for neuroprotection of retinal ganglion cells in the treatment of glaucoma. Life Sci. 2020;243:117303. https://doi.org/10.1016/j.lfs.2020.117303.

    Article  CAS  PubMed  Google Scholar 

  3. Peral A. Contact lenses as drug delivery system for glaucoma: a review. Appl Sci. 2020;10(15):5151. https://doi.org/10.3390/app10155151.

    Article  CAS  Google Scholar 

  4. Sartini F. In vivo efficacy of contact lens drug-delivery systems in glaucoma management. A systematic review. Appl Sci. 2021;11(2):724. https://doi.org/10.3390/app11020724.

    Article  CAS  Google Scholar 

  5. Maulvi FA, Shetty KH, Desai DT, Shah DO, Willcox MDP. Recent advances in ophthalmic preparations: Ocular barriers, dosage forms and routes of administration. Int J Pharm. 2021;608:121105. https://doi.org/10.1016/j.ijpharm.2021.121105.

    Article  CAS  PubMed  Google Scholar 

  6. Oh DJ, Chen JL, Vajaranant TS, Dikopf MS. Brimonidine for the treatment of glaucoma. Expert Opin Pharmacother. 2019;20:115–22. https://doi.org/10.1080/14656566.2018.1544241.

    Article  CAS  PubMed  Google Scholar 

  7. Cantor LB. Brimnidine in the treatment of glaucoma and ocular hypertension. Ther Clin Risk Manag. 2006;2(4):337–46. https://doi.org/10.2147/2Ftcrm.2006.2.4.337.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Alyami H. Nonionic surfactant vesicles (niosomes) for ocular drug delivery: Development, evaluation and toxicological profiling. J Drug Deliv Sci Technol. 2020;60:102069. https://doi.org/10.1016/j.jddst.2020.102069.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  10. Fathala D, Fouad EA, Soliman GM. Latanoprost niosomes as a sustained release ocular delivery system for the management of glaucoma. Drug Dev Ind Pharm. 2020;46:806–13. https://doi.org/10.1080/03639045.2020.1755305.

    Article  CAS  Google Scholar 

  11. Xu J, Ge Y, Bu R. Co-delivery of latanoprost and timolol from micelles-laden contact lenses for the treatment of glaucoma. J Control Release. 2019;305:18–28. https://doi.org/10.1016/j.jconrel.2019.05.025.

    Article  CAS  PubMed  Google Scholar 

  12. Xu W, Wanzhen J. Bimatoprost loaded microemulsion laden contact lens to treat glaucoma. J Drug Deliv Sci Technol. 2019;54:101330. https://doi.org/10.1016/j.jddst.2019.101330.

    Article  CAS  Google Scholar 

  13. Maulvi FA, Patil RJ, Desai AR, Shukla MR, Vaidya RJ, Ranch KM, Vyas BA, Shah SA, Shah DO. Effect of gold nanoparticles on timolol uptake and its release kinetics from contact lenses: In vitro and in vivo evaluation. Acta Biomater. 2019;86:350–62. https://doi.org/10.1016/j.actbio.2019.01.004.

    Article  CAS  PubMed  Google Scholar 

  14. Kumar GP, Rajeshwarrao P. Nonionic surfactant vesicular systems for effective drug delivery—an overview. Acta Pharm Sin B. 2011;1(4):208–19. https://doi.org/10.1016/j.apsb.2011.09.002.

    Article  CAS  Google Scholar 

  15. Verma A. Emerging potential of niosomes in ocular delivery. Expert Opin Drug Deliv. 2021;18:55–71. https://doi.org/10.1080/17425247.2020.1822322.

    Article  CAS  PubMed  Google Scholar 

  16. Gugleva V, Titeva S. Design and in vitro evaluation of doxycycline hyclate niosomes as a potential ocular delivery system. Int J Pharm. 2019;567:118431. https://doi.org/10.1016/j.ijpharm.2019.06.022.

    Article  CAS  PubMed  Google Scholar 

  17. Gupta P, Yadav KS. Formulation and evaluation of brinzolamide encapsulated niosomal in-situ gel for sustained reduction of IOP in rabbits. J Drug Deliv Sci Technol. 2022;67:103004. https://doi.org/10.1016/j.jddst.2021.103004.

    Article  CAS  Google Scholar 

  18. Moiseev RV, Morrison PW. Penetration enhancers in ocular drug delivery. Pharmaceutics. 2019;11(7):321. https://doi.org/10.3390/2Fpharmaceutics11070321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Waqas MK, Sadia H. Development and characterization of niosomal gel of fusidic acid: in-vitro and ex-vivo approaches. Des Monomers Polym. 2022;2022:165–74. https://doi.org/10.1080/2F15685551.2022.2086411.

    Article  Google Scholar 

  20. Khan DH, Bashir S. Process optimization of ecological probe sonication technique for production of rifampicin loaded niosomes. J Drug Deliv Sci Technol. 2019;50:27–33. https://doi.org/10.1016/j.jddst.2019.01.012.

    Article  CAS  Google Scholar 

  21. Verma P, Yadav KS. Quality by design (QbD) enabled and Box-Behnken design assisted approach for formulation of tranexamic acid loaded stratum corneum lipid liposomes. J Drug Deliv Sci Technol. 2023;86:104571. https://doi.org/10.1016/j.jddst.2023.104571.

    Article  CAS  Google Scholar 

  22. Silva LD, Htar TT. Characterization, optimization, and in vitro evaluation of Technetium-99m-labeled niosomes. Int J Nanomed. 2019;14:1101–17. https://doi.org/10.2147/2FIJN.S184912.

    Article  Google Scholar 

  23. Singh KH, Shinde UA. Chitosan nanoparticles for controlled delivery of Brimonidine to the ocular membrane. Pharmazie. 2011;66:594–9. https://doi.org/10.1691/ph.2011.0349.

    Article  CAS  PubMed  Google Scholar 

  24. Bayindir ZS, Yuksel N. Investigation of formulation variables and excipient interaction on the production of niosomes. AAPS PharmSciTech. 2012;13:826–35. https://doi.org/10.1208/2Fs12249-012-9805-4.

    Article  Google Scholar 

  25. Mohamad EA, Fahmy HM. Niosomes and liposomes as promising carriers for dermal delivery of Annona squamosa extract. Braz J Pharm Sci. 2020;56:e18096. https://doi.org/10.1590/s2175-97902019000318096.

    Article  CAS  Google Scholar 

  26. Eldeeb AE, Salah S, Ghorab M. Proniosomal gel-derived niosomes: an approach to sustain and improve the ocular delivery of Brimonidine; formulation, in-vitro characterization, and in-vivo pharmacodynamic study. Drug Deliv. 2019;26:509–21. https://doi.org/10.1080/10717544.2019.1609622.

    Article  CAS  Google Scholar 

  27. Zheng J, Clogston DJ, Patri AK. Dobrovolskaia AM, McNeil SE. Sterilization of silver nanoparticles using standard gamma irradiation procedure affects particle integrity and biocompatibility. J Nanomed Nanotechnol 2011:95–101. https://doi.org/10.4172/2F2157-7439.S5-001.

  28. Padala S, Sripada R, Gundabattula SB, Tadi KJ, Nallamothula PR, Raveshi F, Magharla DD. A comparative study on the efficacy of brinzolamide/timolol versus brinzolamide/brimonidine fixed drug combinations in primary open-angle glaucoma. Future J Pharm Sci. 2020;6(1):1–7.

    Google Scholar 

  29. Dubey A, Prabhu P. Development and investigation of niosomes of Brimonidine and timolol maleate for the treatment of glaucoma. Int J PharmTech Res. 2014;6(3):942–50.

    CAS  Google Scholar 

  30. Maulvi FA, Soni TG, Shah DO. A review on therapeutic contact lenses for ocular drug delivery. Drug Deliv. 2016;23:3017–26. https://doi.org/10.3109/10717544.2016.1138342.

    Article  CAS  PubMed  Google Scholar 

  31. Maulvi FA, et al. Controlled bimatoprost release from graphene oxide laden contact lenses: in vitro and in vivo studies. Colloids Surf B. 2020;208:112096. https://doi.org/10.1016/j.colsurfb.2021.112096.

    Article  CAS  Google Scholar 

  32. Jung HJ, Jaoude MA. Glaucoma therapy by extended release of timolol from nanoparticle loaded. J Control Rel. 2012;2012:82–9. https://doi.org/10.1016/j.jconrel.2012.10.010.

    Article  CAS  Google Scholar 

  33. Nguyen DC. Pharmaceutical-loaded contact lenses as an ocular drug delivery system: A review of critical lens characterization methodologies with reference to ISO standards. Cont Lens Anterior Eye. 2021;44(6):101487. https://doi.org/10.1016/j.clae.2021.101487.

    Article  PubMed  Google Scholar 

  34. Pereira-da-Mota AF, Lopez MV. Atorvastatin-eluting contact lenses: effects of molecular imprinting and sterilization on drug loading and release. Pharmaceutics. 2021;13(5):606. https://doi.org/10.3390/pharmaceutics13050606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Gulsen D, Li CC, Chauhan A. Dispersion of DMPC liposomes in contact lenses for opthalmic drug delivery. Curr Eye Res. 2005;30:1071–80. https://doi.org/10.1080/02713680500346633.

    Article  CAS  PubMed  Google Scholar 

  36. Jain N, Verma A, Jain N. Formulation and investigation of pilocarpine hydrochloride niosomal gels for the treatment of glaucoma: intraocular pressure measurement in white albino rabbits. Drug Deliv. 2020;27:888–99. https://doi.org/10.1080/10717544.2020.1775726.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Elshaer A, et al. Nanoparticle-laden contact lens for controlled ocular delivery of prednisolone: Formulation optimization using statistical experimental design. Pharmaceutics. 2016;8(2):14. https://doi.org/10.3390/pharmaceutics8020014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Basiri L, Rajabzadeh G, Bostan A. α-Tocopherol-loaded niosome prepared by heating method and its release behavior. Food Chem. 2017;221:620–8. https://doi.org/10.1016/j.foodchem.2016.11.129.

    Article  CAS  PubMed  Google Scholar 

  39. Abdelkader H, Ismail S, Kamal A, Alany RG. Preparation of niosomes as an ocular delivery system for naltrexone hydrochloride: Physicochemical characterization. Pharmazie. 2010;65:811–7.

    CAS  PubMed  Google Scholar 

  40. Souza JF, Maia KN. Ocular inserts based on chitosan and Brimonidine: development, characterization and biocompatibility. J Drug Deliv Sci Technol. 2016:21–30. https://doi.org/10.1016/j.jddst.2016.01.008.

  41. Pramod K, Ali J. Unveiling the compatibility of eugenol with formulation excipients by systematic drug-excipient compatibility studies. Jo Anal Sci Technol. 2015. https://doi.org/10.1186/s40543-015-0073-2.

    Article  Google Scholar 

  42. Mohamed HB, El-Shanawany SM, Hamad MA, Elsabahy M. Niosomes: a strategy toward prevention of clinically significant drug incompatibilities. Sci Rep. 2017;7(1):6340. https://doi.org/10.1038/s41598-017-06955-w.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sharma PK, Chauhan MK. Optimization and characterization of Brimonidine Nanoparticles-loaded in situ gel for the treatment of glaucoma. Curr Eye Res. 2021:1703–1716. https://doi.org/10.1080/02713683.2021.1916037.

  44. Gupta U. Spectroscopic studies of cholesterol: Fourier Transform Infra-red and vibrational Frequency Analysis. Materials Focus. 2014:211–217. https://doi.org/10.1166/mat.2014.1161.

  45. Soltys-Robitaille CE. The relationship between contact lens surface charge and in-vitro protein deposition levels. Biomaterials. 2001:3257–3260. https://doi.org/10.1016/S0142-9612(01)00163-6.

  46. Farmoudeh A, Akbari J, Saeedi M. Methylene blue-loaded niosome: preparation, physicochemical characterization, and in vivo wound healing assessment. Drug Deliv Transl Res. 2020. https://doi.org/10.1007/s13346-020-00715-6.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Hao YM, Li K. Entrapment and release difference resulting from hydrogen bonding interactions in niosome. Int J Pharm. 2011:245–253. https://doi.org/10.1016/j.ijpharm.2010.10.027.

  48. Mavaddati MA, Moztarzadeh F, Baghbani F. Effect of formulation and processing variables on dexamethasone entrapment and resease of niosomes. J Clust Sci. 2015:2065–2078. https://doi.org/10.1007/s10876-015-0908-4.

  49. Barakat HS. Vancomycin-eluting niosomes: a new approach to the inhibition of staphylococcal biofilm on abiotic surfaces. AAPS PharmSciTech. 2014:1263–1274. https://doi.org/10.1208/2Fs12249-014-0141-8.

  50. Gharbhavi M, Amani J. Niosome: a promising nanocarrier for natural drug delivery through Blood brain barrier. Adv Pharmacol Sci. 2018:6847971. https://doi.org/10.1155/2018/6847971.

  51. Franco P, Marco ID. Contact lenses as ophthalmic drug delivery systems: a review. Polymers. 2021;13(7):1102. https://doi.org/10.3390/2Fpolym13071102.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Moreddu R, Vigolo D, Yetisen AK. Contact lens technology: from fundamentals to applications. Adv Healthc Mater. 2019;8(15):1900368. https://doi.org/10.1002/adhm.201900368.

    Article  CAS  Google Scholar 

  53. Riley C, Chalmers RL, Pence N. The impact of lens choice in the relief of contcat lens related symptoms and ocular surface findings. Cont Lens Anterior Eye. 2005;23:13–9. https://doi.org/10.1016/j.clae.2004.09.002.

    Article  Google Scholar 

  54. Mun J, Jeong S, Cho S. Drug-eluting contact lens containing cyclosporineloaded cholesterol-hyaluronate micelles for dry eye syndrome. RSC Adv. 2019;9(29):16578–85. https://doi.org/10.1039/C9RA02858G.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kesavan K, Kant S, Singh PN, Pandit JK. Mucoadhesive chitosan-coated cationic microemulsion of dexamethasone for ocular delivery: in vitro and in vivo evaluation. Curr Eye Res. 2013;38(3):342–52. https://doi.org/10.3109/02713683.2012.745879.

    Article  CAS  PubMed  Google Scholar 

  56. Aj R, Hn Y, Sb S. Natural gums as sustained release carriers: development of gastroretentive drug delivery system of ziprasidone HCl. DARU J Pharm Sci. 2012;20:58. https://doi.org/10.1186/2008-2231-20-58.

    Article  CAS  Google Scholar 

  57. Rad MS, Mohajeri SA. Simultaneously load and extended release of betamethasone and ciprofloxacin from Vitamin E-loaded silicone-based soft contact lenses. Curr Eye Res. 2016:1–7. https://doi.org/10.3109/02713683.2015.1107591.

  58. Ammar HO. Nanoemulsion as a potential ophthalmic delivery system for dorzolamide hydrochloride. AAPS PharmSciTEch. 2009:808. https://doi.org/10.1208/s12249-009-9268-4.

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Tripathi, S., Yadav, K.S. Development of brimonidine niosomes laden contact lenses for extended release and promising delivery system in glaucoma treatment. DARU J Pharm Sci 32, 161–175 (2024). https://doi.org/10.1007/s40199-023-00500-z

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