Preparation and in vitro characterization of 9-nitrocamptothecin-loaded long circulating nanoparticles for delivery in cancer patients

Abstract

The purpose in this study was to investigate poly(ethylene glycol)-modified poly (d,l-lactide-co-glycolide) nanoparticles (PLGA-PEG-NPs) loading 9-nitrocamptothecin (9-NC) as a potent anticancer drug. 9-NC is an analog of the natural plant alkaloid camptothecin that has shown high antitumor activity and is currently in the end stage of clinical trial. Unfortunately, at physiological pH, these potent agents undergo a rapid and reversible hydrolysis with the loss of antitumor activity. Previous researchers have shown that the encapsulation of this drug in PLGA nanoparticles could increase its stability and release profile. In this research we investigated PLGA-PEG nanoparticles and their effect on in vitro characteristics of this labile drug. 9-NC-PLGA-PEG nanoparticles with particle size within the range of 148.5 ± 30 nm were prepared by a nanoprecipitation method. The influence of four different independent variables (amount of polymer, percent of emulsifier, internal phase volume, and external phase volume) on nanoparticle drug-loading was studied. Differential scanning calorimetry and X-ray diffractometry were also evaluated for physical characterizing. The results of optimized formulation showed a narrow size distribution, suitable zeta potential (+1.84), and a drug loading of more than 45%. The in vitro drug release from PLGA-PEG NPs showed a sustained release pattern of up to 120 hours and comparing with PLGA-NPs had a significant decrease in initial burst effect. These experimental results indicate that PLGA-PEG-NPs (versus PLGA-NPs) have a better physicochemical characterization and can be developed as a drug carrier in order to treat different malignancies.

Zerumbone-loaded nanostructured lipid carriers: preparation, characterization, and antileukemic effect

“…The experiment was conducted in triplicate and the drug release data were evaluated by zero-order, first-order, and Higuchi equations to determine the release kinetics. 41 In vitro cytotoxic study…”

Development of PLGA-based itraconazole injectable nanospheres for sustained release

“…16 In addition, a 1% (w/v) PLGA solution was prepared by dissolving the PLGA (50:50) in acetone. To get an optimal concentration of the surfactant used to prepare PLGA …”

“…The limit of detection and the limit of quantification were evaluated, based on a signal-to-noise ratio of 6. The accuracy and precision of the intraday and the interday assay were determined by analyzing samples (n=6) with three different concentrations (16,150, and 1,600 ng/mL), using a calibration curve constructed on the same day or three sequential days. The acceptable reproducibility concentration was within ±15%.…”

Preparação de nanopartículas poliméricas a partir de polímeros pré-formados: parte II

“…Então, para uma concentração elevada de polímero na fase orgânica, menor será a velocidade de difusão e maior o tamanho das nanosferas resultantes do fluido. Uma concentração polimérica mais baixa conduz ao aumento da velocidade de difusão do solvente, à redução do tamanho médio das gotículas da dispersão resultante e, em consequência, à obtenção de nanosferas de menores dimensões [32] .…”

“…Segue-se a remoção do solvente orgânico a pressão reduzida, formando-se as nanopartículas, como resultado da difusão rápida do solvente do polímero, através da fase aquosa [31] . A utilização de co-polímeros anfipáticos formados por copolímeros de poli(ácido lático)-co-(ácido glicólico) (PLGA) e cadeias hidrofílicas de polietilenoglicol (PEG) [32] . O método de deslocamento do solvente permite obter nanosferas ou nanocápsulas.…”