The worldwide prevalence of obesity has risen tremendously over the past four decades, and 42% of Americans now live with obesity (body mass index >30 kg/m<sup>2</sup>). Obesity is linked to a shortened lifespan and an increased risk for cardiovascular diseases, type 2 diabetes, and cancer. Current clinical strategies to treat obesity give priority to pharmacotherapy, including FDA-approved anti-obesity medications. Notably, none of these therapies consistently yield long-term reductions in weight, and there are challenges concerning bioavailability and the effective delivery of anti-obesity drugs. The more serious side effects are thought to result from the impacts of these drugs on off-target tissues (non-adipose tissue), particularly the liver and vascular tissues, in patients with obesity-associated comorbidities. Therefore, in the present study, we designed an innovative drug delivery strategy employing nano-scale prodrugs that specifically target cells in the visceral adipose tissue of obese mice when delivered through peritoneal injection. To make this system translational, we used the rotatable central composite design, a response surface model for long-acting injectables (LAIs) biodegradable microspheres. We developed a prototype microsphere sustained-release system and performed in vitro release kinetics studies showing quasi-linear release over one month. We also developed physiomics models to define mechanistic understanding, predictive simulation tools (e.g., PBPK modeling), and biorelevant dissolution methods. The LAI provides an opportunity to reduce administration frequency, improve patient adherence and experience, and reduce healthcare costs.

Model-informed drug development for long-acting injectable to treat obesity

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ACS Fall 2022

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.