Combination of self-assembling system and N,O-Carboxymethyl chitosan improves ocular residence of anti-glaucoma drug
Abstract
Glaucoma is known to be one of the principal causes of vision loss due to elevated intraocular pressure. Currently, latanoprost eye drops is used as first-line treatment for glaucoma; however, it possesses low bioavailability due to rapid precorneal clearance. A novel delivery system with a mucoadhesive property could overcome this problem. Therefore, we attempt to develop a combination of self-assembling latanoprost nanomicelles (Latcel) and a mucoadhesive polymer (N,O-carboxymethyl chitosan: N,O-CMC) to improve the corneal residence time. Latcel was developed using Poloxamer-407 by thin film hydration method, followed by the addition of N,O-CMC using simple solvation to obtain Latcel-CMC and characterized using various physicochemical characterization techniques. The particle size of Latcel-CMC was 94.07 ± 2.48 nm and a zeta potential of -16.03 ± 0.66 mV, with a sustained release for 24h whereas marketed latanoprost drops released 90 % of the drug within 1h. In vitro cytotoxicity studies, HET-CAM, and in vivo Draize test showed the biocompatibility of Latcel-CMC. Cellular uptake studies performed using fluorescein isothiocyanate (FITC) loaded nanomicelles in human corneal epithelial cells indicates the increased cellular uptake as compare to plain FITC solution. In vivo ocular residence time was evaluated in Wistar rats using Indocyanine green (ICG) loaded nanomicelles by an in vivo imaging system (IVIS), indicating Latcel-CMC (8h) has better residence time than plain ICG solution (2h). The Latcel-CMC showed improved corneal residence time and sustained release of latanoprost due to increased mucoadhesion. Thus, the developed N,O-Carboxymethyl chitosan based nanomicelles eye drop could be a better strategy than conventional eye drops for topical delivery of latanoprost to treat glaucoma.
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Latcel-CMC in New Zealand white rabbits confirmed the drug has 24-h continuous release ability and good biocompatibility, and eye retention time is extended to 8 h, much higher than 2 h of the ordinary solution.
“The in vivo experiment in New Zealand white rabbits confirmed that the drug has a 24-h continuous release ability and good biocompatibility, and the eye retention time is extended to 8 h, which is much higher than 2 h of the ordinary solution”
From From design to Deployment: The innovative role of nanomicelles in targeted ophthalmic therapeutics (2025) · cites this paper as [160]
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- Authors
- Kailasam, V., Kumara, B. N., Prasad, K. S., & Nirmal, J.
- Affiliations
- Birla Institute of Technology and Science - Hyderabad Campus (IN)
- Yenepoya University (IN)
- Corresponding author
- Prasad, K. Sudhakara
- Nirmal, Jayabalan
- Venue
- European Journal of Pharmaceutics and Biopharmaceutics
- Publisher
- Elsevier BV
- Published
- 2024-04
- Volume
- 197
- Pages
- 114208
- ISSN
- 0939-6411 (ISSN-L)
- OpenAlex
- W4391617409
- Cited by
- 19
- References
- 61
- Citations by year
- 2026: 2 · 2025: 14 · 2024: 3
- FWCI
- 3.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- European Journal of Pharmaceutics and Biopharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Science and Technology
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Ocular Surface and Contact Lens
- Keywords
- latanoprost, glaucoma, ocular drug delivery, Pluronic F127, N,O-carboxymethyl chitosan, mucoadhesion, ocular residence time, sustained drug release, eye drops, corneal epithelial cells, biocompatibility, topical ocular drug delivery
- MeSH terms
- Latanoprost, Antiglaucoma Agents, Animals, Cornea, Delayed-Action Preparations, Drug Carriers, Glaucoma, Humans, Ophthalmic Solutions, Drug Delivery Systems, Fluorescein-5-isothiocyanate, Rats, Wistar, Chitosan, Rats
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