Abstract
The present research work focused on the development and evaluation of a cationic nanoliposomal formulation of Ciprofloxacin HClfor sustained release ocular drug delivery for the treatment of bacterial endophthalmitis. Conventional ophthalmic formulations of ciprofloxacin exhibit poor ocular bioavailability due to rapid precorneal elimination, nasolacrimal drainage, and limited corneal permeability, resulting in frequent dosing and reduced patient compliance. Therefore, the objective of this work was to develop a stable liposomal delivery system capable of enhancing ocular retention and providing sustained release of ciprofloxacin.
A reverse-phase high-performance liquid chromatography (HPLC) analytical method was used for the quantification of ciprofloxacin hydrochloride. Liposomal formulations were prepared using thin-film hydration followed by active remote loading employing an ammonium sulphate transmembrane gradient. Various formulation parameters including lipid composition and drug-to-lipid ratio were optimized to improve encapsulation efficiency and formulation stability. Initial passive loading studies demonstrated poor encapsulation efficiency (~15%) and drug precipitation, whereas active loading significantly improved drug entrapment (~30%) and formulation reproducibility.
Among the formulations investigated, the 2:1 DPPC (1,2-dipalmitoyl-sn-glycero-3-phopshocholine): DC-Chol (3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol ) formulation at a 20 % w/w drug relative to the lipid composition demonstrated the most favourable balance between encapsulation efficiency, particle size, colloidal stability, and reproducibility. The optimized formulation exhibited nanometric particle size (<300 nm), acceptable polydispersity index (<0.3), and positive zeta
potential (+30-45 mV), supporting successful formulation of the cationic liposomes containing ciprofloxacin. Cytotoxicity studies using ARPE-19 (Adult Retinal Pigmental Epithelial) cells demonstrated acceptable cellular compatibility with cell viability remaining above the recommended safety threshold.
In vitro drug release studies demonstrated sustained ciprofloxacin release over 144 h compared to the rapid release observed from the free drug solution. Release kinetic analysis indicated diffusion-controlled drug release behavior consistent with the Higuchi model and first-order kinetics. The nano liposomal formulation also demonstrated comparable in vitro corneal permeability to the free ciprofloxacin solution, suggesting that further enhancement of the positive surface charge may improve effective permeability (Peff). Overall, the findings of this thesis demonstrate the potential of DPPC/DC-Chol-based cationic nanoliposomes as a promising sustained-release ocular drug delivery system for ciprofloxacin, with potential applications in the management of bacterial ocular infections and postoperative ophthalmic care.