Rapid Dissolvable Microneedles Integrated with Felodipine-Loaded Liposome: Fabrication, Characterizations, in-vitro and ex-vivo Evaluation

Abstract

Felodipine (FD), a calcium channel blocker used to manage hypertension, suffers from poor solubility and low oral bioavailability, which limits its therapeutic efficacy. This study proposes a novel strategy to address this limitation by formulating FD-loaded liposomes (FD-LP) integrated into dissolving microneedles (DMNs), utilizing the biodegradable polymer hydroxypropyl methylcellulose (HPMC) for enhanced transdermal delivery. In the present research, firstly, FD-loaded liposomes were formulated by the thin-film rotary evaporation method and later optimized using Box-Behnken Design (BBD). The optimized FD-LP formulation achieved nanosized vesicles with stable zeta potential and high entrapment efficiency. Methylthiazol tetrazolium (MTT) assay using FD-loaded liposomes against human epidermal keratinocytes (HaCaT) revealed a decrease in cell viability as the concentration of liposomes increased. Secondly, formulation of FD-LP infused into HPMC-based dissolving microneedles to deliver the felodipine transdermally. The resulting FD-LP-DMNs displayed sharp pyramidal microneedles with suitable mechanical strength, effective skin insertion capability, and rapid dissolution of MNs in rat skin. Ex-vivo studies demonstrated the transdermal flux of FD was significantly (4.79 ± 0.03 µg/cm2/hr) improved by FD-LP-DMNs as compared to FD-DMNs. The enhancement ratio of FD-LP-DMNs was 2.77. In conclusion, the integration of FD-loaded liposomes into DMNs shows great promise as a delivery platform for the transdermal administration of FD. This DMN array may serve as a potential approach to a controllable, self-administrative, and rapid transdermal delivery system.