InVitro, Ex Vivo, and In Vivo Evaluation of a Dual pH/Redox Responsive Nanoliposomal Sludge for Transdermal Drug Delivery.

A dual pH/redox responsive copper-glyglycine-prednisolone succinate-loaded nanoliposomal (NL) sludge was successfully synthesized and optimized using a Box-Behnken design of experiments. Preformulation design variables indicated that relative ratios of phospholipids, considerably influences NL size, thus altering the degree of drug loading in the formulation. In vitro evaluation further confirmed optimum release kinetics of the NL sludge, corresponding closely to ex vivo permeation studies, demonstrating effective transdermal delivery of prednisone succinate (PS) through a pig skin model, which closely resembles human skin anatomy. The pH/redox stimuli responsiveness of the NL sludge further demonstrated superior properties in vivo using a Sprague-Dawley rat model. The NL sludge displayed the greatest release of PS within 24 h of evaluation, falling within the acceptable therapeutic range of PS dose efficiency. In vivo results further displayed the greatest absorption of PS under inflammatory induced conditions, thus confirming the unique pH/redox responsive properties of the NL sludge. It was thus confirmed that the copper-glyglycine-prednisolone succinate-loaded NL sludge has significant potential for application in chronic inflammatory conditions such as tumor necrosis factor receptor-associated periodic syndrome (TRAPS), designed to release an effective dose of corticosteroid, as a transdermal drug delivery formulation, for effective therapeutic efficacy.