Formulation and Characterization of Polymeric Nanoparticles Encapsulating Ganciclovir for Improved Ocular Delivery

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Ocular drug delivery continues to be challenging because of dynamic anatomical and physiological barriers such as precorneal drainage, tear turnover and limited corneal permeability in which conventional ophthalmic formulations are limited to <5% ocular bioavailability. Ganciclovir, a potent anti-viral active against cytomegalovirus (CMV) and herpes simplex viruses (HSV-1/HSV-2) is associated with rapid elimination and poor intraocular penetration, requiring frequent dosing. The objective of the present study is to formulate and characterize polymeric nanoparticles encapsulated with ganciclovir to improve precorneal retention and corneal permeation and sustained drug release. Chitosan, a biodegradable and mucoadhesive polymer, was chosen because of its capacity to open the tight junctions transiently and enhance drug penetration. Nanoparticles were produced using the ionic gelation technique using sodium tripolyphosphate (TPP) and optimized by adjusting the polymer concentration and sonication time. Characterization was carried out (particle size, zeta potential, encapsulation efficiency, morphology (SEM), FTIR, DSC, in vitro release, kinetic modelling, and in vivo ocular pharmacokinetics in rabbits). Optimized formulation (F9) showed a particle size of 585.4 nm, zeta potential of +38.3 mV and encapsulation efficiency of 81.1%. Spherical morphology confirmed by SEM. In vitro studies showed biphasic release followed by sustained release for up to 24 hours (90.10%), according to Higuchi kinetics. Stability studies showed no significant alteration in drug release for 90 days. Overall, the study validates the possibility of use of polymeric nanoparticles based on chitosan as an efficient ocular delivery system for ganciclovir, with an improved bioavailability, a longer residence time and a reduced dosing frequency.

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