Cisplatin nanoparticles coated microneedle-array enhances anticancer effect in HNSCC

Abstract

Objectives: Cisplatin (CDDP) is the first-line chemotherapeutic agent for HNSCC and has notable side effects, such as nephrotoxicity, neurotoxicity, and ototoxicity. A major research gap exists in methods for improving its antitumor effects and reducing its systemic side effects. Recently, the microneedle (MN), as a minimally invasive device that can bypass the stratum corneum of the skin or mucosa to deliver drugs transdermally or transmucosally, has attracted increased research interest. We hypothesize that the use of MNs loaded with CDDP nanoparticles (NPs) for local drug delivery can improve the antitumor effects and reduce the side effects of CDDP. Methods: Lipid-coated cisplatin nanoparticles were synthesized through a two-step process including ion exchange and lipid coating. HNSCC cell lines, FaDu, SCC-15 and CAL 27 were used to detect anti-cancer efficiency in vitro. Furthermore, we fabricated lipid-coated cisplatin nanoparticles delivered by dissolving microneedles. For in vivo study, FaDu cells were injected subcutaneously into flank of nude mice. Antitumor effect, side effects and pharmacokinetic study were performed. Results: The synthesized lipid-coated CDDP nanoparticles could enhance the anti-cancer effect on the HNSCC cell lines in vitro. Microneedles could effectively facilitate the transdermal delivery of the synthesized cisplatin nanoparticles. Cisplatin nanoparticles delivered by MN has significantly suppressed tumor growth compared to intraperitoneal administration and locally injection group. Microneedles groups did not show any threat to organs while cisplatin groups induced nephrotoxicity. Conclusions: Microneedle delivered cisplatin nanoparticles could greatly enhance the anti-head and neck cancer treatment via an efficient transdermal delivery and intracellular drug release. Meanwhile, chemotherapy side effects could be decreased by this novel strategy.