title: Activity and in vivo tracking of Amphotericin B loaded PLGA nanoparticles.
abstract: The development of biocompatible polymeric nanoparticles has become an important strategy for optimizing the therapeutic efficacy of many classical drugs, as it may expand their activities, reduce their toxicity, increase their bioactivity and improve biodistribution. In this study, nanoparticles of Amphotericin B entrapped within poly (lactic-co-glycolic) acid and incorporated with dimercaptosuccinic acid (NANO-D-AMB) as a target molecule were evaluated for their physic-chemical characteristics, pharmacokinetics, biocompatibility and antifungal activity. We found high plasma concentrations of Amphotericin B upon treatment with NANO-D-AMB and a high uptake of nanoparticles in the lungs, liver and spleen. NANO-D-AMB exhibited antifungal efficacy against Paracoccidioides brasiliensis and induced much lower cytotoxicity levels compared to D-AMB formulation in vivo and in vitro. Together, these results confirm that NANO-D-AMB improves Amphotericin B delivery and suggest this delivery system as a potential alternative to the use of Amphotericin B sodium deoxycholate.
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: A C O
authors.initials: AC
authors.lastname: Souza
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Nascimento
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: N M
authors.initials: NM
authors.lastname: de Vasconcelos
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Jerônimo
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: I M
authors.initials: IM
authors.lastname: Siqueira
authors.affiliation: Faculty of Agronomy and Veterinary Medicine, University of Brasília, DF, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: R-Santos
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: D O S
authors.initials: DO
authors.lastname: Cintra
authors.affiliation: Biotechnology Department, Health Sciences Faculty, University of Brasília, DF, Brazil.
authors.forename: L L
authors.initials: LL
authors.lastname: Fuscaldi
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: O R
authors.initials: OR
authors.lastname: Pires Júnior
authors.affiliation: Faculty of Agronomy and Veterinary Medicine, University of Brasília, DF, Brazil.
authors.forename: R
authors.initials: R
authors.lastname: Titze-de-Almeida
authors.affiliation: Biotechnology Department, Health Sciences Faculty, University of Brasília, DF, Brazil.
authors.forename: M F
authors.initials: MF
authors.lastname: Borin
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: S N
authors.initials: SN
authors.lastname: Báo
authors.affiliation: Chemistry Department of FFCLRP, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: O P
authors.initials: OP
authors.lastname: Martins
authors.affiliation: Pharmacy Department, Federal University of Minas Gerais, MG, Brazil.
authors.forename: V N
authors.initials: VN
authors.lastname: Cardoso
authors.affiliation: Pharmacy Department, Federal University of Minas Gerais, MG, Brazil.
authors.forename: S O
authors.initials: SO
authors.lastname: Fernandes
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: M R
authors.initials: MR
authors.lastname: Mortari
authors.affiliation: Chemistry Department of FFCLRP, University of São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Tedesco
authors.affiliation: Biotechnology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, GO, Brazil. Electronic address: amaral.nanobio@gmail.com.
authors.forename: A C
authors.initials: AC
authors.lastname: Amaral
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil; Genomic Science and Biotechnology Post-Graduate Program, Catholic University of Brasília, DF, Brazil.
authors.forename: M S S
authors.initials: MS
authors.lastname: Felipe
authors.affiliation: Biology Institute, University of Brasília, DF, Brazil.
authors.forename: A L
authors.initials: AL
authors.lastname: Bocca
mesh_terms: D000666:Amphotericin B / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000935:Antifungal Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D003840:Deoxycholic Acid / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry* / Q000493:pharmacokinetics; D004338:Drug Combinations; D065546:Drug Liberation; D019344:Lactic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D008422:Materials Testing; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010228:Paracoccidioides / Q000187:drug effects / Q000502:physiology; D010229:Paracoccidioidomycosis / Q000188:drug therapy; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000493:pharmacokinetics; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012449:Safety; D004113:Succimer / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D004337:Drug Carriers; D004338:Drug Combinations; D003840:Deoxycholic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination; D004113:Succimer
keywords: Amphotericin B; Antifungal activity; Biodistribution; PLGA nanoparticles