Activities of Biapenem against Mycobacterium tuberculosis in Macrophages and Mice / 生物医学与环境科学（英文）

OBJECTIVE@#To assess the activities of biapenem against multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis.@*METHODS@#Biapenem/clavulanate (BP/CL) was evaluated for in vitro activity against Mycobacterium tuberculosis (Mtb) multidrug-resistant (MDR) isolates, extensively drug-resistant (XDR) isolates, and the H37RV strain. BP/CL activity against the H37Rv strain was assessed in liquid cultures, in macrophages, and in mice..@*RESULTS@#BP/CL exhibited activity against MDR and XDR Mtb isolates in liquid cultures. BP/CL treatment significantly reduced the number of colony forming units (CFU) of Mtb within macrophages compared with control untreated infected macrophages. Notably, BP/CL synergized in pairwise combinations with protionamide, aminosalicylate, and capreomycin to achieve a fractional inhibitory concentration for each pairing of 0.375 in vitro. In a mouse tuberculosis infection model, the efficacy of a cocktail of levofloxacin + pyrazinamide + protionamide + aminosalicylate against Mtb increased when the cocktail was combined with BP/CL, achieving efficacy similar to that of the positive control treatment (isoniazid + rifampin + pyrazinamide) after 2 months of treatment.@*CONCLUSION@#BP/CL may provide a new option to clinically treat MDR tuberculosis.

Preparation and evaluation of lung targeting microspheres for protionamide in vitro and in vivo / 中国药学杂志

OBJECTIVE: To testify the feasibility of targeted delivery of protionamide to lung through the iv administration of the biodegradable poly(lactic-co-glycollic acid) (PLGA) microspheres. METHODS: Based on the single-factor study, the preparation of protionamide-PLGA microspheres was optimized. The surface morphology of the microspheres was observed by scanning electron microscope (SEM). The mean diameter and the size distribution of microsphere, the drug loading, the incorporation efficiency, drug release in vitro, stability and tissue distribution after intravenous administration were also evaluated, respectively. RESULTS: Protionamide-PLGA microspheres were regular and spherical in shape. The average particle size was (9.86 ± 1.38) μm and over 81.53% of the microspheres was in the range of 7-15 μn. The drug loading and encapsulated ratio was (32.70 ± 0.37)% and (8.48 ± 0.24)%, respectively. The in vitro drug release could be well fitted by the Higuchi equation (Q=4.4303t1/2 ± 7.7241, r=0.9913). Compared with the aqueous formulation, the drug level in lung of BALB/C mice in microsphere group was much higher, and also kept for longer time. CONCLUSION: The protionamide-PLGA microspheres prepared in this study show significant sustained release and lung targeting effect.