Amphotericin-B-loaded polymersomes formulation (PAMBO) based on (PEG)₃-PLA copolymers: an in vivo evaluation in a murine model.
This paper deals with in vivo evaluation of a new amphotericin-B-loaded polymersomes (PAMBO) formulation in terms of pharmacokinetics, toxicity, tissue distribution profile, and its efficacy in a murine model of disseminated candidiasis. Pharmacokinetic and tissue distribution studies of the PAMBO showed sustained levels of the drug in plasma as well as in target organs which harbor fungal and leishmanial infection. PAMBO was found to be much less toxic than Fungizone. It was observed that 700% increment in the dose is tolerated without observable toxicity which is supported by survival, biochemical, and histopathological results. PAMBO showed a significant improvement in the survival rate of immunosuppressed mice infected with Candida albicans as compared to control. It also showed better dose to dose (1 mg/kg) efficacy as compared to Fungizone and a significant improvement in the life expectancy at 3 and 5 mg/kg dose levels in the animals. Colony forming unit (CFU) counts in the target organs revealed significant reduction in Candida burden with PAMBO treatment. Kidney, spleen, and lung were cleared of infection, although liver was carrying a very low level of infection. Overall, PAMBO formulation is found to be more efficacious and less toxic in a fungal mice model.
Department of Pharmaceutics, National Institute of Pharmaceutical Education & Research (NIPER), Sector 67, SAS Nagar-160062, India.
Jay Prakash
JP
Jain
Manu
M
Jatana
Arunaloke
A
Chakrabarti
Neeraj
N
Kumar
D000666:Amphotericin B / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D002176:Candida albicans / Q000187:drug effects / Q000472:pathogenicity; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000187:drug effects
D000935:Antifungal Agents; D011108:Polymers; C542623:monomethoxypolyethyleneglycol-polylactide block copolymer; D011092:Polyethylene Glycols; D000666:Amphotericin B