Abstract/Summary

This PhD project was focused on the preparation of semisolid (polyaphrons) and liquid (liposomes) dosage forms for extended retention of topically applied ophthalmic drugs and evaluation of various ex vivo models for ocular research. The formulation and characterisation of four different polyaphrons stabilised with water-soluble polymers (P188, POZ, PQ10, and CMC) were performed. The highest stability was found in polyaphrons stabilised with P188. This finding demonstrates the ability of amphiphilic non-ionic polymers to stabilise the polyaphron structure effectively. The polyaphrons (mixed with 0.5 mg/mL of fluorescein sodium salt) with 0.3% PQ10 by weight of the total polyaphron weight demonstrated the best retention properties on the ex vivo bovine cornea compared to polyaphrons with P188, POZ, PQ10 (0.1% by weight of the total weight), CMC, and negative control (FITC-dextran solution) using a fluorescence-based flow-through method, which might be explained by the electrostatic interaction of positively charged PQ10 with the negatively charged mucins presented on the ocular surface. The toxicological safety of polyaphrons with P188, POZ, PQ10, and CMC was assessed using SMIT and BCOP assays. Next, conventional (CL), PEGylated liposomes with PEG of different molecular weights (LPEG1000, LPEG2000, LPEG3000, and LPEG5000), and liposomes decorated with functionalised maleimide groups (LPEG2000-Mal) were formulated and analysed in this study. The LPEG2000-Mal outperformed CL, LPEG2000, and FITC-dextran solution when tested on the ex vivo bovine conjunctiva. This outcome supports the hypothesis of the improved mucoadhesive properties for LPEG2000-Mal due to the covalent bonds formation with free thiols groups (–SH) of cysteine from the mucin glycoproteins. Also, ocular dimensions were measured for rabbits’, porcine, ovine, and bovine ex vivo eyeballs, along with the corneal epithelium thickness. The ex vivo model selection depends on the type of ocular research. In addition, the protocol of monitoring the polymer thermogelation and release process following intracameral injection was developed.