Enhanced Drug Performance Elicited by Topical and Ocular Nanoparticles

Most of the marketed nanotechnology-based delivery systems use liposomes and nanoemulsions for parenteral administration but are much less exploited for topical and ocular delivery. Owing to their large molecular size and poor aqueous solubility, penetration of cyclopsorin A (CsA) and tacrolimus (TAC) through the skin and cornea is limited. TAC has been used successfully in Vernal KeratoConjunctivitis in various clinical trials. However, there is no ophthalmic product of this drug in the market except Talymus, a suspension marketed only in Japan. Moreover, its water sensitivity, in addition to its high molecular weight (800 Da) represent a challenge for an effective ocular pharmaceutical formulation. TAC was formulated, characterized and tested ex vivo while loaded in PLGA Nanocapsules (NCs) and Nanoemulsions (NEs). Ex vivo penetration experiments performed on excised pig corneas showed an increased ability of NEs and NCs to penetrate the cornea compared to the free drug dissolved in oil. However, following prolonged storage, TAC was not chemically stable in the NEs. Contrarily, lyophilized NCs and a particular NC-2 formulation were stable for at least eight weeks. Further ex vivo MTT toxicity assays of NC-2 suggested that the formulation instilled did not affect the viability of corneal cells. CsA-nanocapsules (NCs) were shown to enhance drug penetration into the various layers of porcine ear skin. Topical application of lyophilized CsA-NCs incorporated within an anhydrous base was evaluated in two animal models, for atopic dermatitis and contact hypersensitivity. The CsA-NCs topical formulation elicited improved efficacy as compared to marketed topical formulations in terms of better preservation of the skin barrier integrity, lower skin thickness variation, decrease of the systemic pro-inflammation markers and reduced skin inflammation. The overall results suggest that these original ocular and topical platforms may provide novel therapeutic tools of clinical significance compared to the existing topical and ocular therapeutic drugs.