Abstract

Herein, cyclosporine A loaded liposomes (CsA-Lips) were fabricated aimed at improving the biocompatibility of the ophthalmic formulation and getting rid of the direct contact of ocular tissues with irritant excipients . Response surface methodology was exploited in order to investigate the influence of miscellaneous factors on the key characteristics of CsA-Lips. Ratio of EPC:CsA, ratio of EPC:Chol, and stirring speed were selected as the independent variables, while size, drug-loading content (DL), and drug-loading content (DL) loss rate were applied as the response variables. In case of the maximal lack-of-fit p-value and minimum sequential p-value, quadratic model was regarded as the fittest model to analyze the data. The correlation of independent variables with response variables was described by three-dimension surface figures. Optimized formulation for CsA-Lips was obtained with ratio of EPC:CsA set as 15, ratio of EPC:Chol set as 2, and stirring speed set as 800 rpm. The particle size of CsA-Lips was 129.2 nm after optimalization while their TEM images exhibited spherical unilamellar vesicles with clearly shell-core structure. CsA released more rapidly from CsA-Lips in comparison with self-made emulsion and Restasis®. Besides, minimum cytotoxicity of CsA-Lips was perceived via both MTT method and LDH method, indicating the excellent compatibility of the ophthalmic formulation. Simultaneously, CsA-Lips showed enhanced nonspecific internalization in the cytoplasm with a time-dose-dependent manner. In conclusion, CsA-Lips could be adhibited as the hopeful ophthalmic drug delivery system clinically for dry eye syndrome (DES).