Optimisation of PCL-HA laden biodegradable nanoparticles containing cyclosporine-A for the treatment of dry eye syndrome: in vitro-in vivo evaluation

Abstract

The purpose of the present study is to develop polycaprolactone (PCL)-hyaluronic acid (HA) laden biodegradable nanoparticles containing cyclosporine-A (CsA) and sustained the release for ophthalmic delivery. The nanoparticles (NPs) were prepared by solvent diffusion technique followed lyophilisation. Optimisation of product variables for nanoparticles was done by central composite design (CCD) with particle size and entrapment efficiency as chosen responses. The developed formulation consisting 1.18% polycaprolactone and 0.16% hyaluronic acid showed 376.6 nm, −0.438 ± 0.137 mV and 40.945 ± 1.561% particle size, zeta potential and entrapment efficiency respectively. However, this formulation was efficient in controlling the drug release in-vitro as well, i.e., 92.59 ± 0.05% cyclosporine-A release at 24 hours. Surface morphology revealed nanoparticles were spherical in shape. Ocular irritancy study showed that formulation was safe and non-irritant. The Cmax of plain drug and biodegradable nanoparticles was found to be 15.802 mg at 6 hrs (mean residence time - MRT) and 19.447 mg at 8 hrs respectively. Area under the curve (AUC) was found to be 79.26 and 113.0 for plain drug and NPs formulation.