Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous Fungizone.
OBJECTIVE
Amphotericin B (AMB), an effective antifungal and antileishmanial agent associated with low oral bioavailability (0.3%) and severe nephrotoxicity, was entrapped into poly(lactide-co-glycolide) (PLGA) nanoparticles to improve the oral bioavailability and to minimize the adverse effects associated with it.


METHODS
The AMB-nanoparticles (AMB-NP) were prepared by nanoprecipitation method employing Vitamin E-TPGS as a stabilizer. In vitro release was carried out using membrane dialysis method. The in vitro hemolytic activity of AMB-NP was evaluated by incubation with red blood cells (RBCs). The acute nephrotoxicity profile and oral bioavailability of AMB-NP were evaluated in rats.


RESULTS
The prepared AMB-NP formulation contained monodispersed particles in the size range of 165.6 +/- 2.9 nm with 34.5 +/- 2.1% entrapment at 10% w/w initial drug loading. AMB-NP formulation showed biphasic drug release, an initial rapid release followed by a sustained release. The AMB-NP formulation exerted lower hemolysis and nephrotoxicity as compared to Fungizone. The relative oral bioavailability of the AMB-NP was found to be approximately 800% as compared to Fungizone.


CONCLUSIONS
Together, these results offer a possibility of treating systemic fungal infection and leishmaniasis with oral AMB-NP, which could revolutionize the infectious disease treatment modalities.
Italia
J L
JL
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, 27 Taylor Street, Glasgow, UK.
Yahya
M M
MM
Singh
D
D
Ravi Kumar
M N V
MN
D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D001682:Biological Availability; D001806:Blood Urea Nitrogen; D003401:Creatine / Q000097:blood; D006461:Hemolysis / Q000187:drug effects; D019344:Lactic Acid; D008297:Male; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology; D010316:Particle Size; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D017207:Rats, Sprague-Dawley
D000935:Antifungal Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B; D003401:Creatine