Hyaluronic acid-based selegiline nanostructured lipid carriers incorporated dissolving microneedles: A localised transdermal delivery strategy for obesity management

Obesity is a multifactorial disorder correlated with metabolic complications. Conventional oral therapy for obesity has limitations due to its extensive hepatic metabolism, poor efficacy, and systemic side effects. A novel nanostructured lipid carrier integrated with dissolving microneedles was developed for the transdermal delivery of selegiline (SEL) for obesity management. Drug-loaded nanostructured lipid carriers (NLCs) were prepared by the solvent injection-ultrasonication method and optimised via central composite design. The obtained optimised formulation had a particle size of 221.9 ± 0.51 nm, PDI of 0.238 ± 0.12, and entrapment efficiency of 78.56 ± 2.67, with an in vitro drug release of 82.95 ± 3.76 over 8 h. Optimised selegiline-loaded NLCs were combined with hyaluronic acid (HA), polyvinyl alcohol (PVA), and polyvinylpyrrolidone (PVP) based dissolving microneedles (DMNs). The tip of the microneedle, which is made up of HA, a biodegradable polymer that can efficiently release the activity of SEL-NLCs into the bloodstream. In addition, the combination of PVA and PVP showed very good flexibility for selegiline release and resistance to adverse effects. The fabricated DMNs were found to have desirable mechanical strength, uniform geometry, and 4.83% moisture content. In vivo studies conducted on 7 groups of Wistar rats revealed that the optimised formulation showed a substantial decrease in body weight, abdominal circumference, triglycerides, and low-density lipoprotein (LDL) levels, with no skin irritation. This emphasises the ability of SEL- NLCs loaded HA-based DMNs as a potent drug delivery system, elevating SEL's anti- obesity activity for the improved management of obesity.