Authors:

Rachel Zheng

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About Paper:

Delamanid, a moderately hydrophobic basic molecule, has shown promise in treating drug-resistant tuberculosis. However, its hydrophobic nature presents challenges for effective drug delivery by limiting its oral efficacy. This research explores the use of nanoparticle encapsulation to improve the bioavailability of delamanid by improving its dissolution kinetics. To achieve the encapsulation of DLM within polymer-stabilized nanoparticles, Flash NanoPrecipitation (FNP), a technique for controlled antisolvent precipitation, was employed. Through FNP, stable DLM nanoparticles ranging in size from 100 to 300 nm were successfully formed and exhibited stability over multiple days. Previous attempts to nanoencapsulate DLM were unsuccessful and predicted to be due to the presence of trifluoromethyl and nitro functional groups. To overcome these challenges, co-encapsulation with vitamin E acetate and PS-b-PEG as the stabilizer were implemented. The co-encapsulation strategy involved incorporating DLM with a strongly hydrophobic co-core, such as vitamin E acetate. It is hypothesized that this approach increases the overall hydrophobicity of the nanoparticle (NP) core, creating nucleation sites that space out the trifluoromethyl and nitro functional groups, thereby facilitating stabilizer attachment. Consequently, the resulting nanoparticles are expected to exhibit increased specific surface area and amorphous drug forms, thereby promoting dissolution and augmenting drug bioavailability. Future work will focus on processing the nanoparticle suspension into a dry powder and testing the drug dissolution kinetics in a simulated intestinal fluid. The outcomes of this study have significant implications for advancing treatment options in drug-resistant TB, potentially leading to enhanced therapeutic outcomes, and combating this global health menace more effectively.

Source:

Purdue University / 2023

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Co-authors:

Rachel Zheng