Hyaluronic acid-based hesperidin nanostructured lipid carriers loaded dissolving microneedles: A localized delivery approach loaded for the management of obesity

Obesity, a persistent imbalance of calories, has become one of the major clinical factors that result in many metabolic disorders. Despite excellent anti-obesity properties, the poor aqueous solubility of hesperidin (HES), a flavonoid, hampers its applicability. To resolve this issue and conquer oral administration's drawbacks, our study has concentrated on encapsulating HES in nanostructured lipid carriers (NLCs) and incorporating the NLCs into microneedles (MNs). By developing HES-loaded NLCs (HES-NLCs) with hyaluronic acid (HA) as a base design to form a microneedle patch (HES-NLCMNP), the study aimed to increase the stability and bioavailability of HES and provide an innovative way for the management of obesity. HES-NLCs were loaded to the microneedle, to promote anti-obesity activity. The microneedle tip, which has been composed of HA, will act as a biodegradable polymer that could effectively deliver the activity of HES-NLC to the blood stream. Furthermore, the base of the microneedle patch composed of polyvinyl alcohol (PVA) offered excellent flexibility, releasing HES and providing resistance to any adverse effects. Analysis revealed that the prepared HES-NLCs have desirable physical characteristics with an extended-release profile. The optimised NLC formulation (F3F) was later incorporated into HA-base-designed MNs that demonstrated mechanical solid integrity and effective skin penetration. In vivo pharmacokinetics significantly improved all parameters with a reduced elimination rate. Physiological, haematological, and antioxidant markers improved in treated rats, with histopathological analysis showing significant tissue alterations. The results suggest that HES-NLCMNP is a promising platform to improve drug effectiveness, patient compliance, and treatment outcomes for obesity.