Characterization and evaluation of BNIPDaoct-loaded PLGA nanoparticles for visceral leishmaniasis: in vitro and in vivo studies.
OBJECTIVE
To overcome the limitation of bisnaphthalimidopropyldiaaminooctane (BNIPDaoct) low physiological solubility and potentially increase its efficiency against visceral leishmaniasis (VL), a delivery system based on poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles was developed.


METHODS
BNIPDaoct-PLGA nanoparticles were prepared by nanoprecipitation and characterized. Anti-Leishmania activity was evaluated using in vitro and in vivo VL infection models.


RESULTS
BNIPDaoct-PLGA nanoparticles were successfully produced and were sized at 156.0 ± 2.8 nm with an encapsulation efficiency of approximately 85%. The PLGA nanoparticles reduced BNIPDaoct cellular toxicity, retained its in vitro anti-leishmanial activity and led to a significant reduction (∼80%) in the parasite burden in the infected mice spleen when compared with the free drug or amphotericin B. In the liver the effect was less pronounced, with a 30-50% reduction observed between the nanoformulation and the BNIPDaoct per se or the amphotericin B, respectively.


CONCLUSIONS
PLGA nanoparticles provide controlled and effective delivery of BNIPDaoct for treatment of VL.
IBMC-INEB, Infection & Immunology Unit-Parasite Disease Group, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal. slima@ibmc.up.pt
Sofia A
SA
Costa Lima
Mariana
M
Resende
Ricardo
R
Silvestre
Joana
J
Tavares
Ali
A
Ouaissi
Paul Kong Thoo
PK
Lin
Anabela
A
Cordeiro-da-Silva
D000818:Animals; D000981:Antiprotozoal Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D002460:Cell Line; D004337:Drug Carriers / Q000737:chemistry*; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D007893:Leishmania donovani / Q000187:drug effects; D007898:Leishmaniasis, Visceral / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D053758:Nanoparticles / Q000737:chemistry*; D053644:Naphthalimides / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D000981:Antiprotozoal Agents; D004337:Drug Carriers; D053644:Naphthalimides; C557289:bisnaphthalimidopropyldiaaminooctane; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid