Adipocyte-targeted delivery of rosiglitazone with localized photothermal therapy for the treatment of diet-induced obesity in mice.

Obesity represents a growing public health concern and is closely associated with metabolic complications such as diabetes and fatty liver disease. Anti-obesity medications currently available have limited efficacy in weight loss and are often accompanied by adverse effects. This study proposes a localized photothermal therapy (PTT) combined with adipocyte-targeted delivery of rosiglitazone (RSG) to address obesity. Specifically, cationic albumin nanoparticles (cNPs) were synthesized to deliver RSG precisely to white adipocytes, stimulating the browning process. An IR780-loaded thermosensitive hydrogel was injected and allowed to gel in situ to afford a subcutaneous reservoir that enables localized PTT and controlled release of RSG cNPs. Notably, cNPs significantly enhanced the internalization efficiency in adipocytes in vitro and prolonged the therapeutic retention in the adipose tissue in vivo. Co-administration of RSG cNPs and PTT substantially reduced fat content, induced browning in white adipose tissue in diet-induced obese mice, and mitigated complications such as insulin resistance, fatty liver, and hyperlipidemia. The increased expression of uncoupling protein 1 contributes to enhancing energy expenditure and facilitating adipose metabolism, thereby effectively combating obesity. This therapeutic approach integrates localized PTT with adipocyte-targeted delivery to combat the global obesity epidemic thus offering a promising solution with reduced systemic toxicity and enhanced efficacy. STATEMENT OF SIGNIFICANCE: Cationic albumin nanoparticles are capable of efficient internalization in adipocytes, which may enhance drug targeting to adipose tissue. The combination of rosiglitazone-loaded cationic albumin nanoparticles and local hyperthermia effectively reduces lipid accumulation in adipocytes and induces an upregulated expression of uncoupling protein 1. The combination therapy effectively inhibits fat accumulation, induces adipocyte browning, and regulates systemic metabolism in diet-induced obese mice.

A Bilayer Microneedle for Modulated Sequential Release of Adrenaline and Lidocaine for Prolonged Local Anesthesia.

Chronic pain emerges as a major global health issue, significantly impacting individuals' health and quality of life. In this study, we designed a bilayer microneedle loaded with lidocaine nanocomposites in the inner layer and adrenaline (Adr) in the outer layer (HCP MNs) for modulated sequential release to achieve prolonged local anesthesia. The obtained HCP MNs featured an intact structure with adequate mechanical strength for efficient skin penetration. The bilayer structure of MNs was evidenced by loading two fluorescent dyes in each layer. Furthermore, these HCP MNs were capable of inducing rapid as well as prolonged local anesthetic effects in guinea pigs. Hence, the bilayer MN coloaded with Adr and lidocaine nanocomposite serves as a promising transdermal delivery platform for chronic pain management.