Alginate modified-PLGA nanoparticles entrapping amikacin and moxifloxacin as a novel host-directed therapy for multidrug-resistant tuberculosis
Abstract
Abstract Polymeric nanoparticles have been widely investigated as a controlled release drug delivery platform for the treatment of tuberculosis (TB). These nanoparticles are readily internalised into macrophages and leads to high intracellular drug concentration. In this study two anti-TB drugs, amikacin and moxifloxacin were encapsulated into PLGA nanoparticles. The novelty of this work includes: (1) the efficient encapsulation of two hydrophilic second-line anti-TB drugs, and (2) intra-macrophage delivery of this combination potentially for rapid treatment of multi-drug resistant TB (MDR-TB). Two water-oil-water (w/o/w) emulsion strategies were employed in this study to produce: (1) alginate coated PLGA nanoparticles, and (2) alginate entrapped PLGA nanoparticles. The average particle size and polydispersity index (PDI) of the alginate coated PLGA nanoparticles were found to be unfavourably high with values of 640 ± 32 nm and 0.63 ± 0.09, respectively. In contrast, the alginate entrapped PLGA nanoparticles were within the desired particle size range of 312–365 nm and the PDI was 0.14– 0.31, and therefore were chosen for subsequent studies. Alginate entrapped nanoparticles exhibited an entrapment of moxifloxacin in the range of 10.1–18.7 μg/mg and an entrapment of amikacin in the range of 15–17.4 μg/mg. On the contrary, non-modified PLGA nanoparticles exhibited a significantly less amikacin loading of 6.2 μg/mg polymer and 4.2 μg/mg of moxifloxacin. The release of alginate…
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