Chitosan/carbomer nanoparticles- laden in situ gel for improved ocular delivery of timolol: in vitro, in vivo, and ex vivo study.

Due to the small capacity of the eye cavity and the rapid drainage of liquid into the nasolacrimal duct, patients must frequently administer the drops. Nanoparticles (NPs) and in situ gel systems have each proven their ability to achieve eye retention independently. In this study, timolol-loaded chitosan-carbomer NPs were prepared using the polyelectrolyte complexation method, and incorporated into a pH-responsive in situ gel system made of carbomer. The rheological behavior of NPs-laden in situ gel was examined at room and physiological conditions. Characteristics such as zeta potential, surface tension, refractive index, mucoadhesive properties, drug release, transcorneal permeability, and intra-ocular pressure (IOP) lowering activity were investigated on NPS and NPs-laden in situ gel formulations. The optimum gained NPs system had an encapsulation efficiency of about 69% with a particle size of 196 nm. The zeta potential of the NP and NPs-laden in situ gel were - 16 and + 11 mV respectively. NPs-laden in situ gel presented enhanced viscosity at physiological pH. All physicochemical properties were acceptable for both formulations. NPs and NPs-laden in situ gel systems proved to sustain drug release. They showed mucoadhesive properties which were greater for NPs-laden in situ gel. IOP reduction by NPs-laden in situ gel was significantly higher and more long-lasting than the timolol solution and NPs. In conclusion, the developed NPs-laden in situ gel is a promising carrier for ocular drug delivery due to the slow release of drug from nanoparticles, its mucoadhesive properties, and high viscosity acquisition in contact with precorneal film, which lead to improved therapeutic efficacy.