Docetaxel Loaded PEG-PLGA Nanoparticles: Optimized Drug Loading, In-vitro Cytotoxicity and In-vivo Antitumor Effect (original) (raw)
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Assessment of release kinetics of Docetaxel loaded PLGA nanoparticles
Asian Journal of Pharmacy and Pharmacology
Objective: The objective of the present study was to formulate and investigate in vitro release kinetics profile of docetaxel loaded poly (lactic-co-glycolic acid) nanoparticulate drug delivery system in order to improvise the solubility of the drug as well as to attain a controlled release drug pattern in pursuit to reduce the toxicity and dosing frequency problems associated with the present marketed formulations. Materials and methods: Preformulation study of docetaxel such as physical properties (melting point, partition coefficient, and solubility), identification (UV and FTIR spectroscopy) and linearly regressed calibration curves for quantification were carried out prior to formulation development. Taking advantage of biodegradable and biocompatible, and FDA approved polymer "poly (lactic-co-glycolic acid)", docetaxel loaded nanoparticles were developed. by emulsification-solvent evaporation technique. The morphology of the docetaxel loaded nanoprticles was observed via scanning electron microscopy (SEM). Synthesized docetaxel loaded nanoprticles were also characterized with regard to their particle diameters, zeta potential, drug loading capacities, and drug release kinetics. Results and conclusion: A nanoparticle formulation of PLGA encapsulating docetaxel was prepared via emulsification-solvent evaporation technique under optimized conditions. The developed formulation showed a favorable particle size below 200 nm for higher retention at tumor site owing to enhanced permeability and retention (EPR) effect. Entrapment efficiency was recorded to be 64.34±1.53%. In vitro studies showed that the docetaxel loaded nanoparticles exhibited a sustained drug release which suggested that nanoparticles are likely to reduce dose and dosing frequency. We also studied release behavior of docetaxel in terms of mechanism and pattern so that these aspects may be of great utility to formulation developers for cancer targeting and NPs development of similar drug. Developed NPs still warrant further investigation for assuring ex-vivo and in-vivo potential.
Paclitaxel-loaded PEGylated PLGA-based nanoparticles: In vitro and in vivo evaluation
Journal of Controlled Release, 2009
The purpose of this study was to develop Cremophor ® EL-free nanoparticles loaded with Paclitaxel (PTX), intended to be intravenously administered, able to improve the therapeutic index of the drug and devoid of the adverse effects of Cremophor ® EL. PTX-loaded PEGylated PLGA-based were prepared by simple emulsion and nanoprecipitation. The incorporation efficiency of PTX was higher with the nanoprecipitation technique. The release behavior of PTX exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release. The in vitro anti-tumoral activity was assessed using the Human Cervix Carcinoma cells (HeLa) by the MTT test and was compared to the commercial formulation Taxol ® and to Cremophor ® EL. When exposed to 25 µg/ml of PTX, the cell viability was lower for PTX-loaded nanoparticles than for Taxol ® (IC 50 5.5 vs 15.5 µg/ ml). Flow cytometry studies showed that the cellular uptake of PTX-loaded nanoparticles was concentration and time dependent. Exposure of HeLa cells to Taxol ® and PTX-loaded nanoparticles induced the same percentage of apoptotic cells. PTX-loaded nanoparticles showed greater tumor growth inhibition effect in vivo on TLT tumor, compared with Taxol ® . Therefore, PTX-loaded nanoparticles may be considered as an effective anticancer drug delivery system for cancer chemotherapy.
American Journal of Analytical Chemistry
Docetaxel is a member of taxan family of antineoplastic agents widely used in cancer chemotherapy. However, application of conventional chemotherapy with commercial formulation has been accompanied with matters of concern regarding drug’s biodistribution, pharmacokinetics, and pharmacodynamics. Polymeric nanoparticles have been widely used as unique drug delivery vehicles to circumvent such problems. Docetaxel-loaded poly (lactide-co-glycolide) (PLGA) and poly (lactide-co-glycolide)-poly (ethylene glycol) (PLGA-PEG) nanoparticles fit well in modifying drug’s pharmacokinetic characteristics as intravenous (IV) sustained-release delivery vehicles. In such circumstances, characterization of nanoparticles in terms of their drug-payload would be a necessary step. The majority of studies have used HPLC analysis method for docetaxel quantitation in polymeric nanoparticles. Herein, a rapid ESI-MS/MS method for quantitative analysis of docetaxel in polymeric matrices of PLGA and PLGA-PEG nan...
Polyglutamic acid-PEG nanocapsules as long circulating carriers for the delivery of docetaxel
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e.V, 2014
Recently we reported for the first time a new type of nanocapsules consisting of an oily core and a polymer shell made of a polyglutamic acid-polyethylene glycol (PEG-PGA) grafted copolymer with a 24% w/w PEG content. The goal of the work presented here has been to develop a new version of these nanocapsules, in which the shell is made of a di-block PEG-PGA copolymer with a 57% w/w PEG content and to evaluate their potential for improving the biodistribution and pharmacokinetics of the anticancer drug docetaxel (DCX). A comparative analysis of the biodistribution of fluorescently labeled PGA-PEG nanocapsules versus PGA nanocapsules or a control nanoemulsion (containing the same oil than the nanocapsules) showed that the nanocapsules, and in particular PEGylated nanocapsules, have significantly higher half-life, MRT (Mean Residence Time) and AUC (Area under the Curve) than the nanoemulsion. On a separate set of experiments, PGA-PEG nanocapsules were loaded with DCX and their antitumor efficacy was evaluated in a xenograft U87MG glioma mouse model. The results showed that the survival rate for mice treated with DCX-loaded nanocapsules was significantly increased over the control Taxotere Ò , while the antitumoral effect of both formulations was comparable (60% tumor growth inhibition with respect to the untreated mice). These results highlight the potential use of these novel nanocapsules as a new drug delivery platform in cancer therapy.
International Journal of Pharmaceutics, 2017
Nanoprecipitation is a simple and increasingly trending method for nanoparticles preparation. The self-assembly feature of poly (ethylene glycol)-poly (lactide-co-glycolic acid) (PEG-PLGA) amphiphilic copolymer into a nanoparticle and its versatile structure makes nanoprecipitation one of the best methods for its preparation. The aim of this study is to review currently available literature for standard preparation of PEG-PLGA nanoparticles using nanoprecipitation technique in order to draw conclusive evidenceto draw conclusive evidence that can guide researchers during formulation development. To achieve this, three databases (Web of Science, Scopus and PubMed) were searched using relevant keywords and the extracted articles were reviewed based on defined inclusion and exclusion criteria. , Data extraction and narrative analysis of the obtained literature was performed when appropriate, along with our laboratory observations to support those claims wherever necessary. As a result of this analysis, reports that matched our criteria conformed to the general facts about nanoprecipitation techniques such as simplicity in procedure, low surfactants requirement, narrow size distribution, and low resulting concentrations. However, these reports showed interesting advantages for using PEG-PLGA as they are frequently reported to be freeze-dried and active pharmaceutical ingredients (APIs) with low hydrophobicity were reported to successfully be encapsulated in the particles.
International Journal of Drug Development and Research, 2010
Purpose: The present study was aimed at preparing and evaluating biodegradable nanoparticles of docetaxel (DTX). Method: Nanoparticles were prepared by emulsification solvent evaporation technique using polylactic-co-glycolide (PLGA) as biodegradable matrix. The formulations were then characterized with respect to size and its surface morphology, zeta potential, entrapment efficiency in vitro drug release profile, stability studies and in vivo tissue distribution study. Results: The formulated DTX-PLGA nanoparticles were oval with diameter ranging from 200 nm to 400 nm. The entrapment efficiency was found to be in the range 51.07% to 62.16%. Highest cumulative percent drug release was observed F-1 (49.24 %) and lowest F-4 (36.25%) in 48 h. Based on the highest regression values (R), all four formulations followed Peppas Korsmeyer model. Formulation F-4 with optimal particle size, high entrapment efficiency and satisfactory in vitro release was selected for in vivo studies. The avera...
International Journal of Biological Macromolecules, 2014
The aim of this paper was to develop and evaluate of paclitaxel (PTX) loaded bovine serum albumin (BSA) nanoparticals using 2 4 factorial designs. Methods: Results: In order to detect the precise effect of the variables and their interactions, design expert software was used. Among the formulations suggested and based on the predicted responses and their desirability indices two formulations were selected as the optimum formulations and evaluated. Based on in-vitro release study formulations show biphasic release pattern with initial burst effect followed by a slower and sustained release. Bovine serum albumin nanoparticals prepared by using desolvation technique method followed by spray drying. In the next step, the effect of different formulation variables, including the amount of polymer BSA (A), Tween 80 (B), Glutarldehyde (C) and Speed (D) on the particle size, entrapment efficiency and % cumulative release of drug was investigated. Based on the type and the variables studied, 16 formulations were designed using factorial design method and were then prepared. The prepared antiparticle was characterized for particle size, drug entrapment, and percentage yield, scanning electron microscopy (SEM), Differential scanning calorimetry, zeta potential and in-vitro release study. Conclusion:
Cellular delivery of PEGylated PLGA nanoparticles
Journal of Pharmacy and Pharmacology, 2012
Objectives The objective of this study was to investigate the efficiency of uptake of PEGylated polylactide-co-gycolide (PLGA) nanoparticles by breast cancer cells. Methods Nanoparticles of PLGA containing various amounts of polyethylene glycol (PEG, 5%-15%) were prepared using a double emulsion solvent evaporation method. The nanoparticles were loaded with coumarin-6 (C6) as a fluorescence marker. The particles were characterized for surface morphology, particle size, zeta potential, and for cellular uptake by 4T1 murine breast cancer cells. Key findings Irrespective of the amount of PEG, all formulations yielded smooth spherical particles. However, a comparison of the particle size of various formulations showed bimodal distribution of particles. Each formulation was later passed through a 1.2 mm filter to obtain target size particles (114-335 nm) with zeta potentials ranging from -2.8 mV to -26.2 mV. While PLGA-PEG di-block (15% PEG) formulation showed significantly higher 4T1 cellular uptake than all other formulations, there was no statistical difference in cellular uptake among PLGA, PLGA-PEG-PLGA tri-block (10% PEG), PLGA-PEG di-block (5% PEG) and PLGA-PEG di-block (10% PEG) nanoparticles. Conclusion These preliminary findings indicated that the nanoparticle formulation prepared with 15% PEGylated PLGA showed maximum cellular uptake due to it having the smallest particle size and lowest zeta potential.
Formulation and evaluation of Paclitaxel loaded PSA-PEG nanoparticles
2011
The main objective of this study was to prepare and evaluate PSA-PEG nanoparticles containing paclitaxel as a model drug by nanoprecipitation method. The influence of different experimental parameters on the particles size, entrapment efficiency, percent drug released etc was evaluated. SEM indicated that nanoparticles have discrete spherical structure without aggregation. The average particle size was found to be 123-405 nm. The particle size of nanoparticles increases gradually with PSA-PEG polymer concentration. The drug content of nanoparticles also increases with increasing polymer concentration up to particular value. The in-vitro drug release behavior from all drug loaded batches was found to be zero order and provided sustained release over a period of 24 hours. Nanoparticles were stored at different temperatures and humidity as per ICH guidelines to check the stability.
Biomaterials, 2004
Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zetapotential analyzer and X-ray photoelectron spectroscopy (XPS). The drug encapsulation efficiency (EE) and in vitro release profile were measured by high-performance liquid chromatography. The effects of various formulation parameters were evaluated. The prepared nanoparticles were found of spherical shape with size less than 100 nm. Zeta potential measurement and XPS analysis demonstrated the presence of PEG layer on the particle surface. Viscosity of the organic phase was found to be one of the main process factors for the size determination. The EE was found to be greatly influenced by the drug loading. The drug release pattern was biphasic with a fast release rate followed by a slow one. The particle suspension exhibited good steric stability in vitro. Such a nanoparticle formulation of paclitaxel can be expected to have long-circulating effects in circulation. r