Critical evaluation of the therapeutic potential of bassic acid incorporated in oil-in-water microemulsions and poly-D,L-lactide nanoparticles against experimental leishmaniasis.
Bassic acid, an unsaturated triterpene acid isolated from Mimusops elangii, was tested for its antileishmanial properties both in vitro and in vivo. The in vitro antileishmanial activity of bassic acid being encouraging, its activity in vivo was evaluated in hamster models of visceral leishmaniasis, both in free form, as well as incorporated in two different delivery systems, viz microemulsions and polylactide nanoparticles. The delivery systems were prepared by published protocols. The percentage intercalation of bassic acid in nanoparticles and microemulsion was found to be about 50 and 100, respectively, when determined at its absorption maxima (lambda(max)) 285 nm (epsilon(m) = 2.3 x 10(2) M(-1) cm(-1)). At an equivalent dose of 2 mg kg(-1) body weight, when injected subcutaneously for a total of six doses in 15 days, bassic acid was found to reduce spleen parasite loads by 45, 62 and 78% in free, microemulsion-incorporated and nanoparticle-incorporated forms, respectively. A comparison of specific biochemical tests related to normal liver and kidney functions revealed that the nanoparticulate form was successful in significantly reducing the hepatotoxicity and nephrotoxicity of the free drug, but the microemulsion delivery system was less effective and toxic to liver and kidney to some extent. Confocal microscopic images of Leishmania donovani promastigotes treated with bassic acid revealed that the drug induced necrotic cell death due to non-specific membrane damage. Because of its high efficacy as well as non-hepatotoxicity and non-nephrotoxicity, the nanoparticulate form of bassic acid may be considered for clinical application in humans rather than the microemulsion incorporated form.
Lala
Sanchaita
S
Indian Institute of Chemical Biology, Biomembrane Division, 4 Raja S. C. Mullick Road, Kolkata 700 032, India.
Gupta
Syamasri
S
Sahu
Niranjan P
NP
Mandal
Debayan
D
Mondal
Nirup B
NB
Moulik
Satya P
SP
Basu
Mukul K
MK
D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006224:Cricetinae; D004337:Drug Carriers / Q000494:pharmacology / Q000627:therapeutic use*; D004655:Emulsions / Q000494:pharmacology / Q000627:therapeutic use; D007893:Leishmania donovani / Q000187:drug effects* / Q000254:growth & development / Q000648:ultrastructure; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D018613:Microscopy, Confocal; D049329:Nanostructures / Q000737:chemistry; D009821:Oils; D021261:Parasitic Sensitivity Tests; D011091:Polyesters / Q000627:therapeutic use; D016896:Treatment Outcome; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D014867:Water
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D004655:Emulsions; D009821:Oils; D011091:Polyesters; D014315:Triterpenes; D014867:Water; C033616:poly(lactide); C071476:bassic acid