Dual Delivery of Cyclosporin A and Etodolac Using Polymeric Nanocapsules in a Rabbit Eye Model: Ocular Biodistribution and Pharmacokinetic Study

Commercially available eye drops are loaded only with a single drug. By using the polymeric nanocapsules, dual delivery of 0.05% w/w cyclosporin A (CsA) and 0.2% w/w etodolac (Edc) was achieved. An ultraperformance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed for determining simultaneously the biodistribution and pharmacokinetic profile of CsA and Edc in ocular tissues. After one single drop instillation of nanocapsules into healthy right eyes of rabbits, the eyeballs were enucleated at 5, 15, 30, 60, and 90 min time periods to separate the 5 different ocular tissues. A liquid/liquid extraction method was used for ocular sample extraction using darunavir as internal standard. Using 3 diverse conditions such as bench-top, autosampler, and freeze-thaw, the stability of the analytes at 3 quality control samples in ocular tissues was also checked. Intra- and interday precisions for both CsA and Edc in multiple ocular tissues were