Microneedle-mediated intradermal nanoparticle delivery: Potential for enhanced local administration of hydrophobic pre-formed photosensitisers

Introduction: To date, 5-aminolevulinic acid (ALA) has been the most widely used agent in topical photodynamic therapy (PDT). However, owing to the poor penetration of ALA into skin, ALA-PDT is inappropriate for difficult-to-treat deep skin neoplasias, such as nodular basal cell carcinoma. An alternative strategy to ALA-PDT is to use pre-formed photosensitisers, which can be activated at longer wavelengths, facilitating enhanced light penetration into skin. Owing to their relatively high molecular weights and often high lipophilicities, these compounds cannot be effectively administered topically. This study aimed to deliver a model hydrophobic dye, Nile red, into the skin using novel microneedle (MN) technology. Materials and methods: Nile red was incorporated into poly-lactide-co-glycolic acid (PLGA) nanoparticles using an emulsion and salting-out process. Polymeric MN arrays were prepared from aqueous blends of the mucoadhesive copolymer Gantrez (R) AN-139 and tailored to contain 1.0 mg of Nile red-loaded PLGA nanoparticles. Intradermal delivery of Nile red was determined in vitro. Results: Uniform 150 nm diameter PLGA nanoparticles were prepared containing 3.87 mu g Nile red / mg of PLGA. Tissue penetration studies using excised porcine skin revealed that high tissue concentrations of Nile red were observed at 1.125 mm (382.63 ng cm(-3)) following MN delivery. Conclusion: For the first time, polymeric microneedles (MN) have been employed to deliver a model lipophilic dye, Nile red, into excised porcine skin. Importantly, this is a one-step delivery strategy for the local delivery of highly hydrophobic agents, which overcomes many of the disadvantages of current delivery strategies. (C) 2010 Elsevier B.V. All rights reserved.