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1.
Int J Nanomedicine ; 12: 8363-8373, 2017.
Article in English | MEDLINE | ID: mdl-29200848

ABSTRACT

This study aimed to synthesize and characterize nanoparticles (NPs) of poly(methyl methacrylate) (PMMA) and evaluate their ability to incorporate plant extracts with antitumor activity and low dissolution in aqueous media. The extract used was n-hexane partition of the methanol extract of Piper cabralanum (PCA-HEX). PMMA NPs were obtained using the mini-emulsion method, which was able to encapsulate almost 100% of PCA-HEX. The synthesized polymeric particles presented with a size of 200 nm and a negative charge. Cytotoxicity tests by MTT and trypan blue assays showed that NPs without PCA-HEX did not kill leukemic cells (K562 cells). NPs containing PCA-HEX were able to enhance cell death when compared to pure extract. The results showed that PMMA NPs could be useful as a drug delivery system as they can enhance the antitumor activity of the PCA-HEX extract by more than 20-fold. PMMA NPs containing plant extracts with antitumor activities may be an alternative to control the evolution of diseases such as leukemia.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Drug Delivery Systems/methods , Emulsions/chemistry , Nanoparticles/chemistry , Piper/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Antineoplastic Agents, Phytogenic/chemistry , Cell Death/drug effects , Drug Screening Assays, Antitumor , Emulsions/administration & dosage , Hexanes/chemistry , Humans , K562 Cells , Nanoparticles/administration & dosage , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Polymethyl Methacrylate/chemistry
2.
Rio de Janeiro; s.n; 2016. 77 p. graf, ilus, tab.
Thesis in Portuguese | LILACS | ID: biblio-983642

ABSTRACT

Fatores que alteram os níveis plasmáticos de substâncias químicas e, por conseguinte, modificam a sua cinética, como por exemplo, a gravidez, podem ter impactos sobre a segurança e eficácia de medicamentos. Em estudo recente, realizado por Carmo (2015), no Laboratório de Toxicologia Ambiental do Departamento de Biologia da Escola Nacional de Saúde Pública da Fundação Oswaldo Cruz (ENSP/FIOCRUZ), foi observado que a concentração plasmática do antimalárico difosfato de primaquina em camundongos fêmeas grávidas DBA/2 era menor do que a concentração do fármaco registrada em igual intervalo de tempo pós-adminstração em camundongos fêmeas não grávidas. Vários estudos sugerem que a diminuição da concentração plasmática de fármacos na gestante pode se dever a um retardo no esvaziamento gástrico e/ou um aumento no volume de distribuição. Alterações do trânsito no trato gastrintestinal podem influenciar diretamente a absorção de fármacos, resultando em absorção mais rápida ou mais lenta. O fármaco analgésico e antipirético paracetamol é absorvido quase que exclusivamente no intestino. Assim a velocidade da sua absorção depende do tempo de esvaziamento gástrico. Fatores tais como alimentação, idade, gravidez e/ou o uso de fármacos que promovem aceleração (metoclopramida) ou o retardo (morfina) da motilidade gastrointestinal, podem influenciar em sua absorção. O objetivo desse trabalho foi desenvolver e padronizar uma metodologia de análise do paracetamol que permitisse investigar o efeito da gravidez sobre o esvaziamento gástrico sobre a cinética de fármacos administrados em pequenos roedores. O método empregado para determinar as concentrações plasmáticas de paracetamol foi a cromatografia em fase líquida de alta eficiência com detector por arranjo de diodos e visualização no ultravioleta (CLAE-DAD-UV), em equipamento Shimadzu Class-VP...


Factors that affect plasma levels of chemicals, and consequently their kinetics, such as pregnancy, can impact on the safety and efficacy of medicines. In a recent study, conducted by Carmo (2015) at the laboratory of Environmental Toxicology (Department of Biological Sciences, National School Public Health, Oswaldo Cruz Foundation -ENSP / FIOCRUZ), it was shown that plasma concentrations of the anti-malarial drug primaquine diphosphate in pregnant female DBA/2 mice were lower than levels found in non pregnant female mice. During pregnancy a delayed gastric emptying and/or an increased volume of distribution may result in lower drug plasma concentrations. Pregnancy-produced changes in the gastrointestinal transit may influence drug absorption. Depending on whether gastric emptying is accelerated or slowed and on the place where drug absorption takes place (stomach or intestines) absorption can be accelerated or slowed. Paracetamol, an analgesic and antipyretic drug, is absorbed almost exclusively in the intestines and is used to investigate the effects of treatment on the gastric emptying rate. Factors such as diet, age, pregnancy or the administration of drugs which accelerate (metoclopramide) or delay (morphine) gastric emptying influence the absorption of paracetamol. The aim of this study was to develop and standardize a methodology to investigate the effect of gastric emptying on the kinetics of drugs administered in small rodents. The methodology used in the analysis of plasma concentrations of paracetamol was High Performance Liquid Chromatography coupled to diode-array detector and visualization on ultraviolet range (HPLC-DAD-UV), using a Shimadzu Class-VP equipment...


Subject(s)
Animals , Acetaminophen , Gastric Emptying , Pregnancy , Rats, Wistar , Chromatography, High Pressure Liquid , Mice , Mice, Inbred DBA , Pharmacokinetics
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