Chitosan-coated bovine serum albumin nanoparticles for topical tetrandrine delivery in glaucoma: in vitro and in vivo assessment

Abstract

Glaucoma is one of the leading causes of blindness. Therapies available suffer from several drawbacks including low bioavailability, repeated administration and poor patient compliance with adverse effects thereafter. In this study, bovine serum albumin nanoparticles (BSA-NPs) coated with chitosan(CS) were developed for the topical delivery of tetrandrine (TET) for glaucoma management. Optimized nanoparticles were prepared by desolvation. pH, BSA, CS and cross-linking agent concentrations effects on BSA-NPs colloidal properties were investigated. CS-BSA-NPs with particle size 237.9 nm and zeta potential 24 mV was selected for further evaluation. EE% exceeded 95% with sustained release profile. In vitro mucoadhesion was evaluated based on changes in viscosity and zeta potential upon incubation with mucin. Ex vivo transcorneal permeation was significantly enhanced for CS coated formulation. In vitro cell culture studies on corneal stromal fibroblasts revealed NPs biocompatibility with enhanced cellular uptake and improved antioxidant and anti-proliferative properties for the CS-coated formulation. Moreover, BSA-NPs were nonirritant as shown by HET-CAM test. Also, bioavailability in rabbit aqueous humor showed 2-fold increase for CS-TET-BSA-NPs compared to TET with a sustained reduction in intraocular pressure in a rabbit glaucoma model. Overall, results suggest CS-BSA-NPs as a promising platform for topical ocular TET delivery in the management of glaucoma.

Recent Progress in Chitosan-Based Nanomedicine for Its Ocular Application in Glaucoma

“…The study showed that higher levels of amination can lead to more positive charges on the surface, likely because there are more amino groups [ 44 ]. Similarly, chitosan-coated tetrandrine containing bovine serum albumin nanoparticles were formulated and optimized for the concentration of BSA, chitosan, glutaraldehyde, and pH to achieve the desired physiochemical properties for the effective treatment of ocular glaucoma [ 45 ]. At pH levels above the isoelectric point (pH > 5) of bovine serum albumin, the net charge of a developed nanoparticle is very negative.…”

“…The developed system helps to improve (4-fold and 1.7-fold) the apparent permeability coefficient compared to tetrandrine suspension and tetrandrine-loaded albumin nanoparticles, respectively. The study also indicated a two-times increase in ocular bioavailability of tetrandrine from developed chitosan-coated albumin nanoparticles compared to tetrandrine suspension and tetrandrine-loaded albumin nanoparticles [ 45 ]. In another study, trimethyl chitosan-coated lipid nanoparticles significantly prolonged the residence of tetrandrine in tears and enhanced ocular absorption as compared to tetrandrine solution [ 62 ].…”

“…It was concluded that chitosan-based nanomedicine is thought to be safe for the in vivo system and could be a promising approach to treat retinopathy, such as glaucoma-related optic nerve degeneration. Radwan et al proved in their investigation that chitosan coating over the nanoformulation system (such as bovine serum albumin nanoparticles) is helpful in further reducing the ocular irritation potential of the nanoformulation system (Illustrated in Figure 10 ) [ 45 ].…”

“…It highlights that the coating of chitosan over the bovine serum albumin nanoparticles is further helpful to reduce the ocular irritation index value compared to bovine serum albumin nanoparticles and tetrandrine suspension. Reproduced from Radwan et al [ 45 ], Informa UK Limited, 2022.…”

Recent Strategies for Ocular Drug Delivery: Promises and Challenges

“…For instance, Radwan et al [12] prepared bovine serum albumin nanoparticles coated with chitosan by the desolvation method for the topical delivery of tetrandrine for management of glaucoma. The optimized formulation had a size of 237.9 nm and zeta potential of 24 mV and high % EE > 95% with a sustained-release drug profile.…”