Targeted chemotherapy of visceral leishmaniasis by lactoferrin-appended amphotericin B-loaded nanoreservoir: in vitro and in vivo studies.
OBJECTIVE
Exploitation of lactoferrin-appended amphotericin B bearing nanoreservoir (LcfPGNP-AmB) for targeted eradication of Leishmania donovani.


METHODS
LcfPGNP-AmB was architechtured through ionic adsorption of lactoferrin over core poly (d,l-lactide-co-glycolide) nanoparticles and characterized. Anti-Leishmania activity in visceral leishmaniasis models, immunomodulatory potential, biodistribution and toxicity profile were also assessed.


RESULTS
LcfPGNP-AmB (size, 196.0 ± 5.28 nm; zeta-potential, +21.7 ± 1.52 mV; encapsulation efficiency, ∼89%) showed reduced toxicity, increased protective proinflammatory mediators expression and down-regulation of disease-promoting cytokines. Biodistribution study illustrated preferential accumulation of LcfPGNP-AmB in liver and spleen. LcfPGNP-AmB showed augmented antileishmanial activity by significantly reducing (∼88%) splenic parasite burden of infected hamsters, compared with commercial-formulations.


CONCLUSIONS
Superior efficacy, desired stability and reliable safety of cost-effective LcfPGNP-AmB, suggest its potential for leishmaniasis therapeutics.
Pharmaceutics Division, CSIR-Central Drug Research Institute, B 10/1, Sector 10, Jankipuram Extension, Lucknow-226031, India.
Shalini
S
Asthana
Pramod K
PK
Gupta
Anil K
AK
Jaiswal
Anuradha
A
Dube
Manish K
MK
Chourasia
D000666:Amphotericin B / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D004337:Drug Carriers / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems; D007781:Lactoferrin / Q000737:chemistry* / Q000378:metabolism; D007893:Leishmania donovani / Q000187:drug effects*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000469:parasitology; D008264:Macrophages / Q000469:parasitology; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D017208:Rats, Wistar; D013154:Spleen / Q000469:parasitology; D014018:Tissue Distribution; D014344:Trypanocidal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
D004337:Drug Carriers; D014344:Trypanocidal Agents; D000666:Amphotericin B; D007781:Lactoferrin
anti-leishmanial activity; antigen-presenting cells; cytokines; macrophages; targeted drug delivery