Novel injectable polypeptide nanoparticle encapsulated siRNA targeting TGF-ß1 and COX-2 for localized fat reduction I: Preclinical in vitro and animal models.

BACKGROUND: Obesity and localized fat accumulation continue to drive the demand for minimally invasive body contouring technologies including injectable compounds for local fat reduction. siRNA offers a potential for an injectable to specifically target and silence genes involved in adipogenesis with minimal inflammatory side effects. AIMS: This study evaluates the efficacy of STP705, an injectable containing siRNA encapsulated within histidine-lysine polypeptide (HKP) nanoparticles targeting transforming growth factor ß1 (TGF-ß1) and cyclooxygenase-2 (COX-2), crucial mediators in adipocyte differentiation and fat retention, using in vitro, porcine, and murine models. METHODS: In vitro experiments on mouse preadipocytes and in vivo trials using Diet Induced Obese (DIO) mice and Yucatan minipigs were conducted to assess the gene silencing efficiency, tissue localization, pharmacodynamics, and safety profile of STP705. RESULTS: STP705 effectively reduced the expression of TGF-ß1 and COX-2, with a notable decrease in adipocyte volume and lipid content without adverse systemic effects. In DIO mice, the HKP-siRNA complex demonstrated precise localization to injected adipose tissue, maintaining significant gene silencing, and detectable levels of siRNA for up to 14 days post-administration. Similar results in minipigs showed a significant reduction in subcutaneous adipose tissue thickness. CONCLUSION: The results of these studies support the use of targeted siRNA therapy specifically targeting TGF-ß1 and COX-2, for localized fat reduction, offering a potential minimally invasive alternative to current fat reduction methods.

Cryolipolysis in the United States-Review of the clinical data.

BACKGROUND: Noninvasive body contouring is becoming more popular in the United States as an alternative to liposuction. The most popular of these methods, cryolipolysis, uses precisely controlled cooling to reduce focal adiposities. The number of cryolipolysis procedures performed annually has experienced rampant growth in United States markets, and the indications have likewise diversified. In light of this change, it is imperative to perform an updated review of available US safety and efficacy data on cryolipolysis. AIMS: To examine the safety and efficacy of cryolipolysis treatments in the United States using data extracted from research performed exclusively at US-based sites. METHODS: In order to identify relevant studies, a literature search was conducted on PubMed using the terms "CoolSculpting" OR "cryolipolysis" OR "lipocryolysis." Articles were manually reviewed to exclude literature reviews, research not performed on humans, studies on experimental combinations of techniques, and any studies not performed in the United States. RESULTS: The initial literature search returned 246 results. Following manual review, a total of 18 studies were selected for data extraction. Mean reduction in fat thickness by ultrasound was 2.0-5.1 mm or 19.6%-32.3%; mean reduction by body caliper was 2.3-7 mm or 14.9%-21.5%. Side effects were mild and transient. Four instances of PAH were documented in 3453 treatment cycles. CONCLUSIONS: Cryolipolysis is a safe, modestly effective method for reducing focal adiposity. Complications are rare and treatable. However, US-based studies are few in number and often of low power and/or quality. More high-quality research is needed for all aspects of cryolipolysis.

Solitary Intrascrotal Plexiform Neurofibroma in a 10-Year-Old Male.

Intrascrotal neurofibromas are extensive tumors that grow from peripheral nerves within the scrotum and are exceedingly rare among the benign extratesticular tumors. Though the risk is low, potential for malignancy and patient discomfort make diagnosis and surgical evaluation imperative. Pediatric neurofibromas are typically only associated with neurofibromatosis type 1. However, herein, we describe a rare case of a benign, intrascrotal plexiform neurofibroma in a 10-year-old male who lacks any stigmata associated with this genetic disorder. Diagnostic and surgical challenges as well as histopathological findings are discussed.