Nanostructured clay particles supplement orlistat action in inhibiting lipid digestion: An in vitro evaluation for the treatment of obesity

Abstract

Obesity is a rapidly growing epidemic, with over one-third of the global population classified as overweight or obese. Consequently, an urgent need exists to develop innovative approaches and technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions technologies that regulate energy uptake, to curb the rising trend in obesity statistics. In this study, nanostructured clay (NSC) particles, fabricated by spray drying delaminated dispersions of commercial clay platelets (Veegum® HS and LAPONITE® XLG), were delivered as complimentary, bioactive excipients with the potent lipase inhibitor, orlistat, for the inhibition of fat (lipid) hydrolysis. Simulated intestinal lipolysis studies were performed by observing changes in free fatty acid concentration and revealed that a combinatorial effect existed when NSC particles were co-administered with orlistat, as evidenced by a 1.2- to 1.6-fold greater inhibitory response over 60 min, compared to dosing orlistat alone. Subsequently, it was determined that a multifaceted approach to lipolysis inhibition was presented, whereby NSC particles adsorbed high degrees of lipid (up to 80% of all lipid species present in lipolysis media) and thus physically shielded the lipid-in-water interface from lipase access, while orlistat covalently attached and blocked the lipase enzyme active site. Thus, the ability for NSC particles to enhance the biopharmaceutical performance and potency of orlistat is hypothesised to translate into promising in vivo pharmacodynamics, where this novel approach is predicted to lead to considerably greater weight reductions for obese patients, compared to dosing orlistat alone.