Nano-Based Drug Delivery Systems of Potent MmpL3 Inhibitors for Tuberculosis Treatment

Pharmaceutics

Gianluigi Cabiddu¹  Alessandro De Logu¹  Carlotta Marianecci²  Mariangela Biava²  Giovanna Poce²  Maria Carafa²  Patrizia Nadia Hanieh²  Federica Rinaldi²  Sara Consalvi²  Jacopo Forte² 

[1] Department of Life and Environmental Sciences, Laboratory of Microbiology, University of Cagliari, Cittadella Universitaria di Monserrato, 09042 Monserrato, Italy;Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Universitaà di Roma, Piazzale Aldo Moro 5, 00185 Rome, Italy;

关键词: nanocarriers;    niosomes;    nanoemulsions;    tuberculosis;   

DOI  :  10.3390/pharmaceutics14030610

来源: DOAJ

【 摘 要 】

Tuberculosis remains one of the world’s deadliest infectious diseases, accounting for nearly 1.3 million deaths every year. Tuberculosis treatment is challenging because of the toxicity, decreased bioavailability at the target site of the conventional drugs and, most importantly, low adherence of patients; this leads to drug resistance. Here, we describe the development of suitable nanocarriers with specific physicochemical properties to efficiently deliver two potent antimycobacterial compounds. We prepared nanoemulsions and niosomes formulations and loaded them with two different MmpL3 inhibitors previously identified (NEs + BM635 and NIs + BM859). NEs + BM635 and NIs + BM859 were deeply characterized for their physicochemical properties and anti-mycobacterial activity. NEs + BM635 and NIs + BM859 showed good hydrodynamic diameter, ζ-Potential, PDI, drug-entrapment efficiency, polarity, and microviscosity and stability. Even though both formulations proved to perform well, only NIs + BM859 showed potent antimycobacterial activity against M. tuberculosis (MIC = 0.6 µM) compared to that of the free compound. This is most probably caused by the fact that BM635, being highly hydrophobic, encounters maximum hindrance in diffusion, whereas BM859, characterized by high solubility in aqueous medium (152 µM), diffuses more easily. The niosomal formulation described in this work may be a useful therapeutic tool for tuberculosis treatment, and further studies will follow to characterize the in vivo behavior of the formulation.

【 授权许可】

Unknown