Synergistic Treatment Of Obesity With Manganese Oxide Nanoparticles And Drug-Loaded Short Fibers

Obesity is a risk factor for type 2 diabetes,cardiovascular disease,cancer and other chronic diseases.At present,anti-obesity drugs are mainly administered systemically by oral and intravenous injection,and have disadvantages such as poor drug targeting,low bioavailability,multiple administration times,and large side effects.The controlled release system of anti-obesity drugs is expected to overcome the above shortcomings.Studies have found that brown adipose tissue plays an important role in regulating energy consumption,glucose homeostasis and insulin sensitivity in vivo.White adipose tissue browning has become an important research direction for safe and effective prevention and treatment of obesity.At the same time,regulating the adipose tissue microenvironment(such as oxidative stress)also has a good effect on obesity and related complications.Therefore,this paper intends to construct short fibers carrying manganese oxide and drug,which are injected into topical subcutaneous fat and release the drug to promote white fat cell browning for a long time,while manganese oxide simulates natural antioxidant enzymes,scavenges oxygen free radicals,regulates oxidative stress level,treats synergistically obesity.In this paper,polylactic acid-polyethylene glycol short fibers carrying browning drug rosiglitazone(RSG)with the length of about 20 ?m was prepared by electrospinning and cryo-cutting technique,and tripolymanganese tetraoxide nanoparticles(MnNP)was fixed on the surface of short fibers through polydopamine to obtain composite short fibers carrying manganese oxide and drug(SF@Rsg-Mn).MnNP maintains high catalytic activity and is relatively stable on the surface of short fibers,while RSG releases 92.5% cumulatively within 30 days.The optimal synergistic ratio of RSG and MnNP to inhibit lipid production was 1:14(m/m)by cellular experiment screening,and the ability of SF@Rsg-Mn to inhibit lipid production,clear reactive oxygen species and promote cell browning was further verified.In vivo anti-obesity results indicate that SF@Rsg-Mn inhibits body weight gain and adipose tissue weight gain inducted by a high-fat diet without causing changes in food intake.Inguinal adipose tissue section staining,reactive oxygen species detection and polymerase chain reaction analysis showed that SF@Rsg-Mn caused adipocytes shrinkage and browning,reduced reactive oxygen species and adipogenic gene expression,and promoted the expression of thermogenic genes.The results of intraperitoneal glucose tolerance test and serological parameters showed that SF@Rsg-Mn improved glucose and lipid metabolism in mice without obvious hepatotoxicity.In summary,the composite short fiber dosage form studied in this paper provides a new method for the controlled release system of new anti-obesity drugs.