Bilayer Dissolving Microneedles Incorporating Hypericin-Loaded Nanocapsules For Improved Localised Photodynamic Therapy

Abstract

Hypericin (Hy) is a potent lipid-soluble photosensitizerhaving broad pharmacological spectrum. Nevertheless, its poor water solubilityleads to its aggregation in the biological systems that consequently diminishesits photodynamic activity (PDA) and its therapeutic applications. Therefore,this study presents novel hydro-solving bilayer microneedle (MN) arraysincorporating Hy-loaded lipid nanocapsules (LNC) to prevent drug aggregation,enhance its delivery and local PDA. The Hy-LNC were prepared by phase inversiontechnique and showed homogenous particle size distribution and highencapsulation efficiency (88.42 ± 0.11%). The bilayer MNs consist of a hydrogelcross-linked, drug-free base plate and a Hy-loaded MN for a one-stepapplication. The dissolving MNs were fabricated from aqueous blends of 10% w/wpolyvinyl alcohol and 30% w/w polyvinyl pyrrolidone by casting and pressure.The MN arrays were characterized for mechanical strength and insertion depth.The bilayer arrays showed good mechanical strength under a compression force of32 N, with a height reduction of 10.14 ± 0.55% and sufficient insertion depthin both Parafilm M® and the excised porcine skin. After 2h of application toexcised pig skin, the MNs were completely dissolved ensuring the delivery ofits payload and the base plate was removed intact free from MN residuals. Inconclusion, the incorporation of Hy-LNC into this novel bilayer MNs overcomeits aggregation and ensured the complete insertion of the drug-loaded MNs. ThisLNC-MN system is promising for improving Hy local availability and thusenhancing its photodynamic application.