Smartly Engineered PEGylated Di-Block Nanopolymeric Micelles: Duo Delivery of Isoniazid and Rifampicin Against Mycobacterium tuberculosis

• Published in: AAPS PharmSciTech 2018-10, Vol.19 (7), p.3237-3248
• Main Authors: Rani, Sarita, Gothwal, Avinash, Khan, Iliyas, Pachouri, Praveen K., Bhaskar, N., Gupta, Umesh D., Chauhan, Devendra S., Gupta, Umesh
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Drug Delivery Systems; Humans; Isoniazid - administration & dosage; Micelles; Mycobacterium tuberculosis - drug effects; Pharmacology/Toxicology; Pharmacy; Polyethylene Glycols - chemistry; Research Article; Rifampin - administration & dosage
• ISSN: 1530-9932; 1530-9932
• DOI: 10.1208/s12249-018-1151-8

In an attempt to deliver multiple drugs through a nanoparticulate platform, the present study was designed to deliver isoniazid (INH) and rifampicin (RMP) together through conjugation/encapsulation approaches using PEG-PLA (polyethylene glycol-poly- l -lactic acid) polymeric micelles. The objective of this study is to identify the preparation and evaluation of PEGylated polymeric micelles with dual drug delivery of INH and RMP for the effective treatment of tuberculosis (TB). Synthesized PEG-PLA di-block-copolymer was further conjugated to INH-forming PEG-PLA-INH (PPI) conjugate. Separately, these conjugates were loaded with RMP building the rifampicin-loaded PEG-PLA-INH polymeric micelles (PMC). The critical micelle concentration (CMC) for the PEG-PLA copolymer was found to be 8.9 ± 0.96 mg/L, and the size and zeta potential were observed to be 187.9 ± 2.68 nm and − 8.15 ± 1.24 mV (0.251 ± 0.042 pdi), respectively. Percent drug loading of PMC was 16.66 ± 1.52 and 23.07 ± 1.05 with entrapment efficiency of 72.30 ± 3.49 and 78.60 ± 2.67% for RMP and INH, respectively. RBC hemolysis capacity of PMC was significantly less than pure RMP and INH. Microplate Alamar blue assay (MABA) along with microscopy showed that the nanoconstructed PMC were more effective than the drugs, and approximately 8-fold reduction in overall minimum inhibitory concentration (MIC) was observed. The prepared duo drug-loaded nano-engineered polymeric micelles were highly effective against sensitive Mycobacterium tuberculosis strains and found to be less hemolytic in nature. The micelles could be further explored (in the future) for in vivo anti-TB studies to establish further to achieve better treatment for TB.