Poly (D,L-lactide-co-glycolide) nanoparticles:Uptake by epithelial cells and cytotoxicity (original) (raw)
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PLGA-based nanoparticles: An overview of biomedical applications
Journal of Controlled Release, 2012
Poly(lactic-co-glycolic acid) (PLGA) is one of the most successfully developed biodegradable polymers. Among the different polymers developed to formulate polymeric nanoparticles, PLGA has attracted considerable attention due to its attractive properties: (i) biodegradability and biocompatibility, (ii) FDA and European Medicine Agency approval in drug delivery systems for parenteral administration, (iii) well described formulations and methods of production adapted to various types of drugs e.g. hydrophilic or hydrophobic small molecules or macromolecules, (iv) protection of drug from degradation, (v) possibility of sustained release, (vi) possibility to modify surface properties to provide stealthness and/or better interaction with biological materials and (vii) possibility to target nanoparticles to specific organs or cells. This review presents why PLGA has been chosen to design nanoparticles as drug delivery systems in various biomedical applications such as vaccination, cancer, inflammation and other diseases. This review focuses on the understanding of specific characteristics exploited by PLGA-based nanoparticles to target a specific organ or tissue or specific cells.
In vivo evaluation of the biodistribution and safety of PLGA nanoparticles as drug delivery systems
Nanomedicine-nanotechnology Biology and Medicine, 2010
The remarkable physicochemical properties of particles in the nanometer range have been proven to address many challenges in the field of science. However, the possible toxic effects of these particles have raised some concerns. The aim of this article is to evaluate the effects of poly(lactide-co-glycolide) (PLGA) nanoparticles in vitro and in vivo compared to industrial nanoparticles of a similar size range such as zinc oxide, ferrous oxide, and fumed silica. An in vitro cytotoxicity study was conducted to assess the cell viability following exposure to PLGA nanoparticles. Viability was determined by means of a WST assay, wherein cell viability of greater than 75% was observed for both PLGA and amorphous fumed silica particles and ferrous oxide, but was significantly reduced for zinc oxide particles. In vivo toxicity assays were performed via histopathological evaluation, and no specific anatomical pathological changes or tissue damage was observed in the tissues of Balb/C mice. The extent of tissue distribution and retention following oral administration of PLGA particles was analyzed for 7 days. After 7 days, the particles remained detectable in the brain, heart, kidney, liver, lungs, and spleen. The results show that a mean percentage (40.04%) of the particles were localized in the liver, 25.97% in the kidney, and 12.86% in the brain. The lowest percentage was observed in the spleen. Thus, based on these assays, it can be concluded that the toxic effects observed with various industrial nanoparticles will not be observed with particles made of synthetic polymers such as PLGA when applied in the field of nanomedicine. Furthermore, the biodistribution of the particles warrants surface modification of the particles to avoid higher particle localization in the liver.
Study on uptake of PLA-Pluronic P85-PLA nanoparticles with Caco-2 cells
Proceedings of the 2015 International Conference on Advanced Engineering Materials and Technology, 2015
We have shown that insulin-loaded Poly(lactic acid)-b-Pluronic-b-poly(lactic acid) nanoparticles (PLA-P85-PLA-NPs) had the hypoglycemic effect after oral administration on diabetic mice. In the present work, free insulin (INS) as controls, the influence of some factors such as time, temperature, pH level, and INS concentration on the uptake efficacy of PLA-P85-PLA-NPs as drug carriers were investigated through a Caco-2 cells. The micrographs of Caco-2 cell model were observed by microscopy. The cytotoxicity of PLA-P85-PLA-NPs in vitro was evaluated by MTT assay. The insulin concentrations in Caco-2 cells were determined by high-performance liquid chromatography (HPLC). Compared with INS groups, PLA-P85-PLA-NPs uptake was not controlled by pH levels. PLA-P85-PLA-NPs can be uptake by Caco-2 cells, and the absorption of PLA-P85-PLA-NPs is dependent on the concentration and incubation time. INS-loaded PLA-P85-PLA-NPs significantly enhanced insulin absorption. These results suggest that PLA-P85-PLA-NPs were more efficient than individual drugs into Caco-2 cells in a short period of time, and PLA-P85-PLA-NPs might be a useful drug carrier for proteins and peptides.
ABSTRACTIn this study, it was aimed to investigate characteristics and intracellular delivery of two different-sizedPLGA nanoparticles in ouzo region by considering number of nanoparticles. To determine the effect offormulation parameters on average particle size, Dil labeled nanoparticles were prepared using a three-factor, two-level full factorial statistical experimental design. PLGA230(230.8 ± 4.32 nm) and PLGA160(157.9± 6.16 nm) nanoparticles were obtained by altering polymer amount based on experimentaldesign results and characterized. Same number of PLGA230and PLGA160nanoparticles per cell wereapplied onto HEK293 cells; then, cytotoxicity, uptake kinetics and mechanism were evaluated by flowcytometry and fluorescent microscopy. Also same weight of PLGA230and PLGA160nanoparticles wereapplied and cellular uptake of these nanoparticles was evaluated. It was found that PLGA230nanopar-ticles had higher encapsulation efficiency and slower dye release compared to PLGA160nanoparticles.When they were applied at same counts per cell, PLGA230nanoparticles displayed faster and higherintracellular dye transfer than PLGA160nanoparticles. On the other hand, PLGA160appeared to be amore effective vehicle than PLGA230when applied at the same weight concentration. It was also shownthat for both nanoparticles, HEK293 cells employed macropinocytic, caveolae- and clathrin-mediatedendocytic pathways
Iranian Journal of Pharmaceutical Research : IJPR, 2011
The uptake and transport of 9-nitrocamptothecin (9-NC), a potent anticancer agent, across Caco-2 cell monolayers was studied as a free and PLGA nanoparticle loaded drug. Different sizes (110 to 950 nm) of 9-nitrocamptothecin nanoparticles using poly (lactic-glycolic acid) were prepared by via the nanoprecipitation method. The transport of nanoparticles across the Caco-2 cell monolayer as a function of incubation time and concentration was evaluated for each different nanoparticle formulation. The amount of 9-NC transported from the apical to the basolateral side and the uptake of the drug into the cells was determined by HPLC. The uptake of intact nanoparticles into Caco-2 cells was visualized by confocal laser scanning microscopy using 6-coumarin as a fluorescent marker. The study demonstrated that Caco-2 cell uptake and transport of encapsulated 9-nitrocamptothecin is significantly affected by the diameter of the carrier and incubation time. In addition it was shown to be independ...
Journal of Biomedical Materials Research Part A, 2015
Polymeric nanoparticles (NPs) are known to facilitate intracellular uptake of drugs to improve their efficacy, with minimum bioreactivity. The goal of this study was to assess cellular uptake and trafficking of PLGA NPs and chitosan (Chi)-covered PLGA NPs in Madin-Darby bovine kidney (MDBK) and human colorectal adenocarcinoma (Colo 205) cells. Both PLGA and Chi-PLGA NPs were not cytotoxic to the studied cells at concentrations up to 2500 lg/mL. The positive charge conferred by the chitosan deposition on the PLGA NPs improved NPs uptake by MDBK cells. In this cell line, Chi-PLGA NPs colocalized partially with early endo-somes compartment and showed a more consistent perinuclear localization than PLGA NPs. Kinetic uptake of PLGA NPs by Colo 205 was slower than that by MDBK cells, detected only at 24 h, exceeding that of Chi-PLGA NPs. This study offers new insights on NP interaction with target cells supporting the use of NPs as novel nutraceuticals/drug delivery systems in metabolic disorders or cancer therapy. V
Evaluation of Cyto- and Genotoxicity of Poly(lactide-co-glycolide) Nanoparticles
Journal of Polymers and the Environment, 2011
This work reports on an analysis of the cytoand genotoxicity of poly(lactide-co-glycolide) polymer nanoparticles, in an attempt to evaluate their mutagenic effects. Fibroblast (3T3) and human lymphocyte cell cultures were exposed to solutions containing three different concentrations of nanoparticles (5.4, 54 and 540 lg/mL, polymer mass/volume of solution). The nanoparticles were characterized in terms of their hydrodynamic diameters, zeta potentials and polydispersity indices. The morphology of the particles was determined by atomic force microscopy. The PLGA nanospheres presented a size of 95 nm, a zeta potential of -20 mV and a spherical morphology. Cellular viability assays using fibroblast cells showed no significant alterations compared with the negative control. A cytogenetic analysis of human lymphocyte cells showed no significant changes in the mitotic index in relation to the control, indicating that in the concentration range tested, the particles used in the experimental models did not present cyto-or genotoxicity. For the tests conducted in this work we can conclude that biodegradable and biocompatible PLGA nanospheres are not toxic in the cell cultures tested (fibroblast and lymphocyte cells) and in the range of concentrations employed. The results provide new information concerning the toxic effects of particles produced using PLGA.
Biomaterials, 2005
This study evaluated cellular uptake of polymeric nanoparticles by using Caco-2 cells, a human colon adenocarcinoma cell line, as an in vitro model with the aim to apply nanoparticles of biodegradable polymers for oral chemotherapy. The feasibility was demonstrated by showing the localization and quantification of the cell uptake of fluorescent polystyrene nanoparticles of standard size and poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with polyvinyl alcohol (PVA) or vitamin E TPGS. Coumarin-6 loaded PLGA nanoparticles were prepared by a modified solvent extraction/evaporation method and characterized by laser light scattering for size and size distribution, scanning electron microscopy (SEM) for surface morphology, zeta-potential for surface charge, and spectrofluorometry for fluorescent molecule release from the nanoparticles. The effects of particle size and particle surface coating on the cellular uptake of the nanoparticles were quantified by spectrofluorometric measurement. Cellular uptake of vitamin E TPGS-coated PLGA nanoparticles showed 1.4 folds higher than that of PVA-coated PLGA nanoparticles and 4-6 folds higher than that of nude polystyrene nanoparticles. Images of confocal laser scanning microscopy, cryo-SEM and transmission electron microscopy clearly evidenced the internalization of nanoparticles by the Caco-2 cells, showing that surface modification of PLGA nanoparticles with vitamin E TPGS notably improved the cellular uptake. It is highly feasible for nanoparticles of biodegradable polymers to be applied to promote oral chemotherapy.
PLGA nanoparticles containing various anticancer agents and tumour delivery by EPR effect
Advanced Drug Delivery Reviews, 2011
As mortality due to cancer continues to rise, advances in nanotechnology have significantly become an effective approach for achieving efficient drug targeting to tumour tissues by circumventing all the shortcomings of conventional chemotherapy. During the past decade, the importance of polymeric drugdelivery systems in oncology has grown exponentially. In this context, poly(lactic-co-glycolic acid) (PLGA) is a widely used polymer for fabricating 'nanoparticles' because of biocompatibility, long-standing track record in biomedical applications and well-documented utility for sustained drug release, and hence has been the centre of focus for developing drug-loaded nanoparticles for cancer therapy. Such PLGA nanoparticles have also been used to develop proteins and peptides for nanomedicine, and nanovaccines, as well as a nanoparticle-based drug-and gene-delivery system for cancer therapy, and nanoantigens and growth factors. These drug-loaded nanoparticles extravasate through the tumour vasculature, delivering their payload into the cells by the enhanced permeability and retention (EPR) effect, thereby increasing their therapeutic effect. Ongoing research about drug-loaded nanoparticles and their delivery by the EPR effect to the tumour tissues has been elucidated in this review with clarity.
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.