Development and in vitro evaluation of Letrozole loaded biodegradable nanoparticles for breast cancer therapy

Abstract

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% to 82%). 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.Uniterms: Breast cancer/therapy. Letrozole. Biodegradable nanoparticles.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% a 82%). 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. Unitermos: Câncer de mama/terapia. Letrozol. Nanopartícula biodegradável.

Tissue inhibitor of matrix metalloproteinases-1 loaded poly(lactic-co-glycolic acid) nanoparticles for delivery across the blood&ndash;brain barrier

“…19,25 The PDI and zeta potential were found to increase with the increase in PLGA concentration ( Table 1). The results are in consensus with results published by Dey et al 26 The zeta potential of TIMP-1-NP PLGA3 formulation was -19.8±0.8 mV.…”

Co-encapsulation of human serum albumin and superparamagnetic iron oxide in PLGA nanoparticles: Part II. Effect of process variables on protein model drug encapsulation efficiency

“…Moreover, an increase in particle size increases the length of diffusional pathways into the aqueous phase, thereby reducing the drug loss through diffusion and increasing the drug content (Budhian et al 2007). Dey et al have also found that encapsulation efficiency of nanoparticles increased from about 68 to 86% with the increment of their mean diameter from 64 nm to 255 nm (Dey et al 2009). Similar results were found by Gorner et al (Gorner et al 1999) where drug encapsulation efficiency grew with the increase in the particle size from about 19% for small particles to about 34% for medium and up to about 57% for large nanospheres which also complies with our earlier result (Feczko et al 2011) and strongly supports our present finding.…”

“…The lower encapsulation efficiencies obtained with the smaller particles was explained by the larger surface area of smaller droplets. Hence, during the emulsification step, a more direct contact between internal and external phases occurred which resulted in higher loss of model drug (HSA) by diffusion to the external medium (Dey et al 2009). Inversely, for larger droplets, the surface area per unit mass is comparatively smaller.…”

Pullulan as a stabilizer agent of polymeric nanocapsules for drug delivery

“…According to the literature, systems presenting spherical geometry, n=0.43 indicates Fickian diffusion, while n≥0.85 is related to case II transport (Peppas, 1985). Values between these limits suggest anomalous transport, i.e., the drug release initially depends on the polymer relaxation followed by Fickian diffusion (Dey et al, 2009).…”