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.
Subject(s)
Amphotericin B/chemistry , Amphotericin B/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Deoxycholic Acid/chemistry , Deoxycholic Acid/pharmacology , Drug Carriers/chemistry , Lactic Acid/chemistry , Nanoparticles/chemistry , Polyglycolic Acid/chemistry , Amphotericin B/adverse effects , Amphotericin B/therapeutic use , Animals , Antifungal Agents/adverse effects , Antifungal Agents/therapeutic use , Deoxycholic Acid/adverse effects , Deoxycholic Acid/therapeutic use , Drug Carriers/pharmacokinetics , Drug Combinations , Drug Liberation , Lactic Acid/pharmacokinetics , Materials Testing , Mice , Paracoccidioides/drug effects , Paracoccidioides/physiology , Paracoccidioidomycosis/drug therapy , Polyglycolic Acid/pharmacokinetics , Polylactic Acid-Polyglycolic Acid Copolymer , Safety , Succimer/chemistry , Tissue DistributionABSTRACT
In Brazil, the center of cassava origin, cassava landraces have acquired through their domestication a large diversity in relation to many economic traits such as high content of carotenoids and excellent palatability among other characters. One of these clones, which has been grown by indigenous Brazilian farmers and is now being maintained in the University of Brasília gene bank, showed a high level of lycopene content (5 mg/kg viz. a viz. zero in common cultivars, and 12-20 mg/kg in tomato, a lycopene-rich vegetable). A second landrace called UnB 400 had a high content of b-carotene, which reached 4 mg/kg.
Subject(s)
Genetic Variation , Carotenoids/analysis , Manihot/genetics , Brazil , Chromatography, High Pressure Liquid , Manihot/chemistryABSTRACT
In Brazil, where puffer fish are considered poisonous, there are few documented cases on human consumption and consequent poisoning. In this study, toxicity of two puffer fish species from the Brazilian coast was examined. Specimens of Sphoeroides spengleri and Lagocephalus laevigatus were caught in Säo Sebastiäo Channel (North coast of Säo Paulo State, Brazil) between January 1996 and May 1997. Acidic ethanol extracts from muscle and skin plus viscera were tested for mice acute toxicity using the standard method of Kawabata. Polar extracts of S. spengleri showed high toxicity up to 946 MU/g. Extracts from L. laevigatus showed very low levels of toxicity, never exceeding 1.7 MU/g. All extracts from both species blocked amielinic nerve fiber evoked impulses of crustacean legs; this effect reverted on washing similar to the standard tetrodotoxin TTX. The aqueous extract solutions were partially purified using an ionic exchange column (Amberlit GC-50) followed by treatment with activated charcoal (Norit-A). The presence of TTX and their analogs in the semi-purified extracts were confirmed by HPLC and mass spectrometry (MALDI-TOF).
