Hyaluronic acid modified chitosan nanoparticles for effective management of glaucoma: development, characterization, and evaluation

Abstract

In clinical practices, solution of dorzolamide hydrochloride (DH) and timolol maléate (TM) is recommended for the treatment of glaucoma. However, low drug-contact time and poor ocular bioavailability of drugs due to drainage of solution, tear turnover and its dilution or lacrimation limits its uses. In addition, systemic absorption of TM may induce undesirable cardiovascular side effects. Chitosan (CS) is a polycationic biodegradable polymer which provides sustained and local delivery of drugs to the ocular sites. Hyaluronic acid (HA) also provides synergistic effect for mucoadhesion in association with chitosan. In the present study, hyaluronic acid modified chitosan nanoparticles (CS-HA-NPs) loaded with TM and DH were developed and characterized. The CS-HA-NPs were evaluated for size, shape, zeta potential, entrapment efficiency, and mucoadhesive strength. The in vitro release study was also performed in PBS pH 7.4. The ocular irritation potential of CS-HA-NPs was estimated using draize test on albino rabbits. A significant reduction in IOP level was obtained using CS-HA-NPs as compared to plain solution of drug and a comparable higher reduction in IOP level was observed as to CS-NPs. These results suggest that HA potentialy enhance the mucoadhesiveness and efficiency of CS-NPs and may be promising carrier for ocular drug delivery.

PLGA Microparticles Entrapping Chitosan-Based Nanoparticles for the Ocular Delivery of Ranibizumab

“…The size was relatively similar to another study utilizing nanoparticles in PLGA microparticles which reported a nanoparticle size of 513 nm (50) . Empty chit/TPP particles were significantly larger than chitosan particles (345.5 ± 2.5 and 40.1 ± 3 nm, respectively, p = 1.79 x 10 -8 ) and previously reported chit/TPP particles of sizes up to 226 nm (51) . This is due to the use of a higher chitosan Mw and chit/TPP ratio of 10:1 compared 4:1 (51) as these parameters have been reported to influence the particle size (52) .…”

Nanotechnology Applications for Glaucoma

“…In in vivo rabbit studies, chitosan NPs encapsulating timolol have been shown to be more effective in lowering IOP as compared with a drug solution. 10 In another study, the subconjuctival administration of microspheres encapsulating the drug exhibited sustained drug release for up to 3 months in in vitro conditions. 11 Similarly, a contact lens loaded with 5% 1:1 timolol: propoxylated glyceryl triacylate NPs continued drug release for up to 1 month under in vitro conditions (Fig.…”

Nanoparticles for drug delivery to the anterior segment of the eye

“…The combination of these properties makes polysaccharides versatile biopolymers for ocular drug delivery [71, 84–89]. Drugs such as cyclosporine A (CsA) [90], dorzolamide hydrochloride [91, 92], pramipexole hydrochloride [91], acyclovir [93], 5-flurouracil [94], carteolol [92], gatifloxacin [95], betamethasone sodium phosphate [96], gene [97], pilocarpine [98], econazole nitrate [99], natamycin [100], daptomycin [89], amphotericin B [101], celecoxib [102], timolol maleate [103, 104], fluconazole [105], sodium diclofenac [106], and tropicamide [107] were loaded into nanoparticles made of polysaccharides for ocular delivery. The release of the drugs from these hydrophilic polymer nanoparticle matrices relies on various factors such as polymer hydration, solvent penetration, drug diffusion, drug dissolution, and/or polymer erosion [95].…”