Preparation and Evaluation of Nanolipid Carriers of Bedaquiline- In vitro Evaluation and in silico Prediction

Abstract

Background: Bedaquiline, a potent antitubercular drug used in the treatment of multidrug-resistant strains, suffers from low oral bioavailability, a slow onset of therapeutic action, and side effects. This investigation proposes the development of nanocarriers for the drug to improve drug release and estimate its effect on oral absorption through an in-silico model. Initially, a custom design was investigated to estimate the effects of composition and process on the entrapment and particle size of the carriers. The nanocarriers were subjected to studies on surface characteristics, surface morphology, thermal properties, drug release, ex vivo permeation, and antimicrobial efficacy. In silico predictions of bioavailability and pharmacokinetic parameters of the optimized formulation were conducted using GastroPlus® software. Results: The study revealed that bedaquiline entrapped in nano lipid carriers (65.5 nm) of glyceryl behenate and palm oil effectively increased the rate of drug release by more than 80% and led to a 3.5-fold increase in antimicrobial activity against Mycobacterium tuberculosis. Intestinal permeation was enhanced by 3.7 times. Predictions using GastroPlus® software indicated that the nano lipid carrier of bedaquiline could be a promising method for improving the drug's efficacy with better localization in the gastrointestinal compartments and improved pharmacokinetics, achieving 93% bioavailability. Conclusion: It can be concluded that bedaquiline nanocarriers in a lipid matrix can serve as an effective tool for enhancing the efficacy of bedaquiline in the treatment of tuberculosis.