Lipolysis And Anti-inflammation Of Drug-loaded Short Fibers For Obesity Treatment

Obesity is a metabolic disease closely related to health,causing various metabolic disorders.At present,the treatment of obesity is mainly oral medication.However most of the clinical diet pills are accompanied by side effects such as dizziness,nausea,and insomnia.It is necessary to design a drug delivery system of targeting adipose tissue to improve bioavailability and reduce systemic side effects.The paper constructed two lengths of injectable drug-loaded fibers,based on local subcutaneous injection and targeting group-mediated dual targeting,respectively,targeting adipocytes and macrophages through lipolysis and regulation of M1/M2 ratio are combined to treat obesity.Using maleic anhydride-modified polylactic acid-polyethylene glycol（MPELA）as the carrier material,the length of about 20μm short fibers carried raspberry ketone（Rk）were prepared by electrospinning combined with cryo-cutting technique,and polypeptide（ATS）which targets adipocyte was surface-modified to obtain ^AtsF_Rk.And the length of about 1μm short fibers carried chrysin（Chr）were prepared by the same technique,and hyaluronic acid（HA）was surface-modified to obtain ^HaR_Chr.The fiber surface grafting rate and drug release behavior of ^AtsF_Rk and ^HaR_Chr were investigated in vitro.The modification of the targeting group improved the phagocytosis effect of macrophages on ^HaR_Chr,and increased the conversion of M1 macrophages to M2.^AtsF_Rk not only made mature adipocyte lipolysis,but also effectively improved the secretion of insulin-sensitive factor adiponectin by adipocytes under the action of anti-inflammatory conditioned medium.In vivo anti-obesity evaluation,^HaR_Chr/^AtsF_Rk inhibited the body weight gain and reduced the weight of adipose tissue which induced by high-fat diet without affecting the intake of food,improved lipid metabolism and no toxic damage to the liver.By analyzing the inguinal adipose tissue H&E section staining and polymerase chain reaction（PCR）results,^HaR_Chr/^AtsF_Rk reduced the sizes of adipocytes,inhibited the expression of pro-inflammatory gene TNF-α,and improved the expression of anti-inflammatory gene IL-10 and insulin-sensitive gene adiponectin.The above studies show that cell-targeted drug-loaded short fibers have anti-inflammatory and lipolytic effects in adipose tissue,which is of latent applied value on the treatment of obesity.