Curcumin/zeolitic imidazolate framework-8 nanoparticle-integrated microneedles for pH-responsive treatment of skin disorders

Abstract

A feasible strategy of on-demand drug delivery for the treatment of dermal inflammation under low-pH conditions is proposed, employing zeolitic imidazolate framework-8 (ZIF-8) as a pH-responsive nanoparticle and curcumin (CCM) as a model drug. To overcome the low bioavailability of topically treated drug, a microneedle (MN) form is used to incorporate CCM and ZIF-8. Taking advantage of the fact that ZIF-8 degrades under acidic conditions, CCM is embedded in porous ZIF-8 nanoparticles such that CCM is released when ZIF-8 comes into contact with an acidic dermal fluid at the inflammation site, and this CCM-encapsulated ZIF-8 (CCMZIF) is incorporated into water-dissolvable poly(vinyl pyrrolidone) MN. The ZIF-8 shows a high loading capacity (similar to 40.5%) of CCM through chemical bonding and physical adsorption. From in vitro tests with both a buffered solution and porcine skin, CCM from the CCMZIF MN is released in a higher amount at pH 5.0 than at pH 7.4, demonstrating the capability of the pH-responsive release of the drug when needed at inflammatory sites. The analytical investigation conducted here reveals that an acidic environment triggers the structural degradation of ZIF-8, allowing the release of the chemically bonded CCM. Cytotoxicity and stability tests demonstrate the good biocompatibility and bioavailability of ZIF-8. This study highlights the analytical discussion of the encapsulation and release mechanism of CCM in a ZIF-8-implemented MN drug delivery platform. The results demonstrate an advanced on-demand therapeutic strategy for skin disorder treatment.