Journal of Microencapsulation, Vol.38, No.2, 108-123, 2021
Dual antitubercular drug loaded liposomes for macrophage targeting: development, characterisation, ex vivo and in vivo assessment
Aim The present study was conducted to formulate and investigate liposomes for the dual drug delivery based on anti-tubercular drug(s) combination i.e. Isoniazid (INH) and Rifampicin (RIF). Materials and methods Mannosylated and non mannosylated liposomes were prepared by lipid thin film hydration method, using DSPC: Chol at a molar ratio 6:4 while in case of mannosylated liposomes DSPC: Chol: Man-C4-Chol at a molar ratio 6.0:3.5:0.5 were used and extensively characterised. The particle size and zeta potential were recorded to be 1.29 +/- 0.24 mu m and -9.1 +/- 0.11 mV. The drug entrapment (%) was recorded to be 84.7 +/- 1.25% for Rifampicin and 31.8 +/- 0.12% for Isoniazid. Results The antitubercular activity studied in Balb/C mice was maximum in the case of mannosylated liposomes. The biodistribution studies also revealed higher drug(s) concentration (accumulation) maintained over a protracted period. Conclusions The liposomal preparations are passively as well as actively uptaken by the alveolar macrophages which are the cellular tropics of infection. The mannosylated liposomes appear to be a potential carrier for dual drug delivery and targeted antitubercular therapy.
Keywords:Mycobacterium tuberculosis;infectious disease;mannosylated liposomes;macrophages;phagocytosis;combination drug therapy;active targeting