Revamping the corneal permeability and antiglaucoma therapeutic potential of brinzolamide using transniosomes: optimization, in vitro and preclinical evaluation

Abstract

Aim: This study aims to explore potential of transniosomes, a hybrid vesicular system, as ocular drug-delivery vehicle. Materials & methods: Thin-film hydration technique was used to fabricate brinzolamide-loaded transniosomes (BRZ-TN) and optimized using Box–Behnken design, further exhaustively characterized for physicochemical evaluations, deformability, drug release, permeation and preclinical evaluations for antiglaucoma activity. Results: The BRZ-TN showed ultradeformability (deformability index: 5.71), exhibiting sustained drug release without irritation (irritancy score: 0) and high permeability compared with the marketed formulation or free drug suspension. The extensive in vivo investigations affirmed effective targeted delivery of transniosomes, with brinzolamide reducing intraocular pressure potentially. Conclusion: Our findings anticipated that BRZ-TN is a promising therapeutic nanocarrier for effectively delivering cargo to targeted sites by crossing corneal barriers.

Summary points

• Ocular drug delivery is an arduous task due to presence of several static and dynamic barriers.

• This research work presents the development and comprehensive investigation of a hyphenated colloidal system as a cutting-edge drug-delivery platform for efficient glaucoma treatment.

• Transniosomes are highly deformable hybrid vesicles possessing advantages of conventional vesicular systems and capable of improving corneal permeability.

• Brinzolamide-loaded transniosomes (BRZ-TN) were prepared and optimized using Box–Behnken design with a hypothesis to overcome aqueous insolubility of drug and promote corneal permeation.

• BRZ-TN showed a deformability index of 5.91, that is, highly elastic in nature, and proved its squeezability by passing through cornea efficiently, observed in confocal laser scanning microscope imaging.

• BRZ-TN exhibited permeation of 89.17 ± 4.39% with drug flux twice that of marketed formulation and apparent permeability of 0.044 in ex vivo permeation studies.

• Subsequent in vivo investigation carried out on New Zealand rabbits provides compelling evidence of enhanced therapeutic efficacy of BRZ-TN with 36% intraocular pressure reduction in 6 h.

• The developed BRZ-TN has the potential to serve as a superior alternative for glaucoma management.

Keywords: :

• brinzolamide
• glaucoma
• nanotechnology
• ocular drug-delivery system
• transniosomes

Author contributions

RK Patil and V Srivastava: writing (original draft), methodology, formal analysis, data curation. V Srivastava and R Bhawale: writing (review and editing), data analysis. KP Tryphena and DK Khatri: data curation. N Doijad: animal facility information writing. NK Mehra: supervision, resources, project administration, funding acquisition, formal analysis, data curation, conceptualization.

Financial disclosure

NK Mehra would like to acknowledge the Department of Science and Technology, New Delhi for the research grant (File no. DST/NM/NS/2021/405) under the nanomission scheme. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Competing interests disclosure

The authors have no competing interests or relevant affiliations with any organization or entity with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Writing disclosure

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval. The animal study was approved by the Institutional Animal Ethics Committee protocol no. NIP/11/2022/PE/527.

Acknowledgments

The authors would like to acknowledge the Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad (Ministry of Chemical and Fertilizers, India) for providing extending facilities during this manuscript (manuscript communication no. NIPER-H/2022).