RESUMO
Radioprotective agents are synthetic compounds or natural products that are immediately administrated before irradiation to reduce injuries caused by ionizing radiation. Toxicity, short duration, and the unfavorable routes of administration, have prevented the widespread use of most radioprotective agents in practice. This study aimed to evaluate the use of slowly release- long circulation biodegradable polymer Poly(lactide-co-glycolide) (PLGA) as carrier for certain water-soluble radioprotective agents. Penicillamine and Potassium Iodide (KI) were selected as examples of radioprotectors which can be used to protect against both internal radionuclide (chronic radiation exposure) and external-beam irradiation (acute radiation exposure). Emulsion-solvent evaporation method (ESE) was used to prepare hydrophilic-drug loaded PLGA Nanoparticles (PLGA- NPs) in an efficient and reproducible manner. The radioprotective efficacy was assessed by 30 days-survival percentage, relative body weights, and (liver & spleen) total cell counts. Results revealed that single oral administration of Penicillamine-NPs or KINPs was effective as free drug (for 5 successive days) which indicate that PLGA-NPs could be used to modulate radioprotective drug activity in biological system, and to improve drug efficacy in different body organs for longer duration than the equal dose of free drug.
RESUMO
The objectives of our study were to prepare and evaluate a biodegradable nanoparticulate system of Letrozole (LTZ) intended for breast cancer therapy. LTZ loaded poly(lactide-co-glycolide) nanoparticles (LTZ-PLGA-NPs) were prepared by emulsion-solvent evaporation method using methylene chloride and polyvinyl alcohol. Percentage of drug (with respect to polymer) was selected as formulation variable. LTZ-PLGA-NPs were characterized by particle size, zeta potential, infrared spectra, drug entrapment efficiency and in vitro release. Sonication was done with an ultrasound pulse sonicator at 70 W, 30 kHz for 90 sec to produce stable NPs of mean size range from 64 nm to 255 nm with high entrapment efficiency (68 percent to 82 percent). Percentage of drug significantly influenced particle size, entrapment efficiency and release (p <0.05). The system sustained release of LTZ significantly and further investigation could exhibit its potential usefulness in breast cancer therapy.
Os objetivos de nosso estudo foram preparar e avaliar o sistema de nanopartícula biodegradável de letrozol na terapia de câncer mamário. Nanopartículas de poli(lactídeo-co-glicolídeo) carregadas com LTZ (LTZ-PLGA-NPs) foram preparadas pelo método de emulsão-evaporação de solvente, utilizando dicloro metano e álcool polivinílico. A porcentagem do fármaco (com relação ao polímero) foi selecionada como variável da formulação. LTZ-PLGA-NPs foram caracterizadas pelo tamanho da partícula, potencial zeta, espectros no infravermelho, eficiência de inclusão e liberação in vitro. A sonicação foi realizada com sonicador de ultrassom, de pulso a 70W e 30 kHz por 90 segundos para produzir NPs estáveis, de faixa de tamanho médio de 64 nm a 266 nm, com alta eficiência de inclusão (68 por cento a 82 por cento). A porcentagem do fármaco foi significativamente influenciada pelo tamanho da partícula, eficiência de inclusão e liberação (p<0,05). O sistema controlou significativamente a liberação de LTZ e estudos posteriores poderiam mostrar sua utilidade potencial na terapia de câncer de mama.