Back to Search
Start Over
Polarity-sensitive nanocarrier for oral delivery of Sb(V) and treatment of cutaneous leishmaniasis
- Source :
- International Journal of Nanomedicine
- Publication Year :
- 2016
- Publisher :
- Informa UK Limited, 2016.
-
Abstract
- Juliane S Lanza,1 Flaviana R Fernandes,1 José D Corrêa-Júnior,2 José MC Vilela,3 Rogério Magalhães-Paniago,4 Lucas AM Ferreira,5 Margareth S Andrade,3 Cynthia Demicheli,6 Maria N Melo,7 Frédéric Frézard1 1Department of Physiology and Biophysics, 2Department of Morphology, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), 3Innovation and Technology Center SENAI FIEMG – Campus CETEC, 4Department of Physics, Instituto de Ciências Exatas (ICEX), 5Department of Pharmaceutical Products, Faculty of Pharmacy, Universidade Federal de Minas Gerais (UFMG), 6Department of Chemistry, Instituto de Ciências Exatas (ICEX), 7Department of Parasitology, Instituto de Ciências Biológicas (ICB), Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, Brazil Abstract: There is a great need for orally active drugs for the treatment of the neglected tropical disease leishmaniasis. Amphiphilic Sb(V) complexes, such as 1:3 Sb–N-octanoyl-N-methylglucamide complex (SbL8), are promising drug candidates. It has been previously reported that SbL8 forms kinetically stabilized nanoassemblies in water and that this simple dispersion exhibits antileishmanial activity when given by oral route to a murine model of visceral leishmaniasis. The main objective of the present work was to interfere in the structural organization of these nanoassemblies so as to investigate their influence on the oral bioavailability of Sb, and ultimately, optimize an oral formulation of SbL8 for the treatment of cutaneous leishmaniasis. The structural organization of SbL8 nanoassemblies was manipulated through addition of propylene glycol (PG) to the aqueous dispersion of SbL8. The presence of 50% (v/v) PG resulted in the loss of hydrophobic microenvironment, as evidenced by fluorescence probing. However, nanostructures were still present, as demonstrated by dynamic light scattering, small-angle X-ray scattering, and atomic force microscopy (AFM). A remarkable property of these nanoassemblies, as revealed by AFM analysis, is the flexibility of their supramolecular organization, which showed changes as a function of the solvent and substrate polarities. The formulation of SbL8 in 1:1 water:PG given orally to mice promoted significantly higher and more sustained serum levels of Sb, when compared to SbL8 in water. The new formulation, when given as repeated doses (200mg Sb/kg/day) to BALB/c mice infected with Leishmania amazonensis, was significantly more effective in reducing the lesion parasite burden, compared to SbL8 in water, and even, the conventional drug Glucantime® given intraperitoneally at the same dose. In conclusion, this work introduces a new concept of polarity-sensitive nanocarrier that was successfully applied to optimize an oral formulation of Sb(V) for treating cutaneous leishmaniasis. Keywords: propylene glycol, antimony, Leishmania amazonensis, AFM, amphiphilic complex, SAXS
- Subjects :
- Antimony
0301 basic medicine
Meglumine antimoniate
Administration, Oral
Pharmaceutical Science
Pharmacology
Microscopy, Atomic Force
X-Ray Diffraction
International Journal of Nanomedicine
Drug Discovery
Original Research
media_common
Drug Carriers
Mice, Inbred BALB C
Meglumine Antimoniate
SAXS
General Medicine
Treatment Outcome
propylene glycol
Female
AFM
Drug carrier
amphiphilic complex
Hydrophobic and Hydrophilic Interactions
medicine.drug
Drug
Materials science
media_common.quotation_subject
030106 microbiology
Antiprotozoal Agents
Biophysics
Leishmaniasis, Cutaneous
Bioengineering
Biomaterials
03 medical and health sciences
Meglumine
Cutaneous leishmaniasis
Scattering, Small Angle
Organometallic Compounds
medicine
Animals
Organic Chemistry
Leishmaniasis
medicine.disease
Bioavailability
Disease Models, Animal
Visceral leishmaniasis
Solvents
Nanoparticles
Nanocarriers
Leishmania amazonensis
Subjects
Details
- ISSN :
- 11782013
- Database :
- OpenAIRE
- Journal :
- International Journal of Nanomedicine
- Accession number :
- edsair.doi.dedup.....aec1c48739386eca2770bf0e2b10e0c1