Adipose tissue–targeted liposomal drug delivery system for treatment of obesity

Abstract

Introduction: Obesity is now becoming a pandemic, with potentially disastrous consequences for human health. However, there are no drugs or combinations of drugs for treating obesity that are both safe and highly effective. One possible approach for solving this problem is to deliver anti-obesity drugs to adipose tissue accurately. Previous papers reported that prohibitin targeting peptide (PTP)-modified nanoparticles are selectively targeted to adipose tissue. Herein, we used PTP-modified liposomes to encapsulate triiodothyronine (T3) to achieve adipose selective transport. Methods: DSPE-PEG-PTP was synthesised and PTP-conjugated liposomes were prepared. Then T3 was loaded in liposomes to prepare T3-PTP-Lip. Transmission electron microscopy, dynamic light scattering, and high-performance liquid chromatography were used to characterise T3-PTP-Lip. Live imaging and fluorospectrophotometry were used to measure the adipose tissue targeting ability. Pharmacokinetic analysis was used to investigate the residence time of T3-PTP-Lip. The effect of T3-PTP-Lip on the metabolism of mice and adipose tissue was measured by metabolic cage and seahorse bioanalyser, respectively. Results: Mass spectrometry and nuclear magnetic resonance spectroscopy results confirmed the successful synthesis of DSPE-PEG-PTP. Transmission electron microscopy and dynamic light scattering showed that T3-PTP-Lip was formed with a particle size of 105 nm. Compared with conventional liposome, T3-PTP-Lip displayed significantly enhanced enrichment in adipose tissue. Pharmacokinetic analysis showed that T3-PTP-Lip had a high residence time in adipose tissue. In addition, compared with other groups, T3-PTP-Lip had a higher ability to enhance the metabolism rates of mice and adipose tissue. Conclusion: The selective delivery and efficient action of T3-PTP-Lip suggests that it might serve as a prototype for anti-obesity drugs.