Fluorescent labeling of degradable poly(lactide-co-glycolide) for cellular nanoparticles tracking in living cells (original) (raw)
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Polymeric nanomedicines based on poly(lactide) and poly(lactide-co-glycolide)
Current Opinion in Solid State and Materials Science, 2012
Small molecule chemotherapeutics often have undesired physiochemical and pharmacological properties, such as low solubility, severe side effect and narrow therapeutic index. To address these challenges, polymeric nanomedicine drug delivery technology has been routinely employed, in particular with the use of biodegradable and biocompatible polyesters, such as poly(lactide) (PLA) and poly(lactide-co-glycolide) (PLGA). Here we review the development and use of PLA and PLGA for the delivery of chemotherapeutic agents in the forms of polymer-drug conjugates and nanoconjugates.
Journal of controlled release : official journal of the Controlled Release Society, 2008
Biodegradable nano/microparticles of poly(D,L-lactide-co-glycolide) (PLGA) and PLGA-based polymers are widely explored as carriers for controlled delivery of macromolecular therapeutics such as proteins, peptides, vaccines, genes, antigens, growth factors, etc. These devices are mainly produced by emulsion or double-emulsion technique followed by solvent evaporation or spray drying. Drug encapsulation, particle size, additives added during formulation, molecular weight, ratio of lactide to glycolide moieties in PLGA and surface morphology could influence the release characteristics. Encapsulation efficiency and release rates through nano/microparticle-mediated drug delivery devices can be optimized to improve their therapeutic efficacy. In this review, important findings of the past decade on the encapsulation and release profiles of macromolecular therapeutics from PLGA and PLGA-based nano/microparticles are discussed critically in relation to nature and type of bioactive molecule,...
Lactide-glycolide polymers as nano-dimensional carriers for drugs
International Journal of Biomedical Nanoscience and Nanotechnology, 2010
Biodegradable polymer poly (D, L-lactide-co-glycolide) as drug-carriers has been a preferred candidate in recent years for developing controlled/sustained release drug delivery systems especially of nano-dimensions due to the favourable physico-chemical characteristics and varieties available of the polymer. Efforts have been in progress to develop nanocarriers based on the polymer to maximise the bio-availability and efficacy of conventional/new extensively versatile drug molecules with minimum side-effects, provide pre-programmed drug release, prolonged duration of drug action and deliver drug at the site of action. This review describes recent work utilising biodegradable polymer poly (D, L-lactide-co-glycolide) for controlled drug delivery, focusing on nanoparticulate delivery systems to shed lights on the present status and advancement of research on nanoformulations with this biodegradable synthetic polymer, mechanism of their cellular uptake and their safety concern. The review highlights the characteristics of the polymers in context to nanoparticles and updates the progress of research in the field in an abridged manner.
Science China Chemistry, 2013
Recent work regarding the Layer by Layer (LbL) engineering of poly(lactide-co-glycolide) nanoparticles (PLGA NPs) is reviewed here. The LbL engineering of PLGA NPs is applied as a means of generating advanced drug delivery devices with tailored recognition, protection, cargo and release properties. LbL in combination with covalent chemistry is used to attach PEG and folic acid to control cell uptake and direct it towards cancer cells. LbL coatings composed of chitosan and alginate show low protein interactions and can be used as an alternative to Pegylation. The assembly on top of LbL coatings of lipid layers composed of variable percentages of 1,2-dioleoyl-sn-glycero-3-choline (DOPC) and 1,2-dioleoyl-sn-glycero-3-phospho-L-serine (DOPS) increases NP uptake and directs the NPs towards the endoplasmic reticulum. The antibody anti-TNF-α is encapsulated forming a complex with alginate that is assembled LbL on top of PLGA NPs. The antibody is released in cell culture following first order kinetics. The release kinetics of encapsulated molecules inside PLGA NPs are studied when the PLGA NPs are coated via LbL with different polyelectrolytes. The intracellular release of encapsulated Doxorubicin is studied in the HepG2 cell line by means of Fluorescence Lifetime Imaging.
Polylactide-co-glycolide nanoparticles for controlled delivery of anticancer agents
International Journal of Nanomedicine, 2011
The effectiveness of anticancer agents may be hindered by low solubility in water, poor permeability, and high efflux from cells. Nanomaterials have been used to enable drug delivery with lower toxicity to healthy cells and enhanced drug delivery to tumor cells. Different nanoparticles have been developed using different polymers with or without surface modification to target tumor cells both passively and/or actively. Polylactide-co-glycolide (PLGA), a biodegradable polyester approved for human use, has been used extensively. Here we report on recent developments concerning PLGA nanoparticles prepared for cancer treatment. We review the methods used for the preparation and characterization of PLGA nanoparticles and their applications in the delivery of a number of active agents. Increasing experience in the field of preparation, characterization, and in vivo application of PLGA nanoparticles has provided the necessary momentum for promising future use of these agents in cancer treatment, with higher efficacy and fewer side effects.
Conjugated poly(D,L-lactide-co-glycolide) for the preparation of in vivo detectable nanoparticles
Biomaterials, 2005
Cellular localization of nanoparticles (Np) represents an important target in the understanding of their distribution after endovenous injection. The need of suitable devices and methodologies capable to detect Np in tissues or in cellular districts can be satisfied by Np which have to be easily recognizable by simple methods. Conjugations of poly(D,L-lactide-co-glycolide) with fluorescein and biotin allow fluorescent and immuno-histochemically active Np to be obtained. The fluorescein Np are detectable using fluorescent microscopy whereas biotin Np can be detected by optical microscopy after streptavidin-biotin-peroxidase complexation. In vivo experiments confirm the ability of these particles to be easily detected in the brain parenchyma or in the liver cell population according to the infusion pathway. r
Characterization of biodegradable poly(d,l-lactide-co-glycolide) polymers and microspheres
Journal of Pharmaceutical and Biomedical Analysis, 1995
Objective: Bacteriochlorophyll-a (BChl-a) was incorporated into nanoparticles of poly(D,L-lactide-co-glycolide) (PLGA), in order to evaluate this photosensitizer when associated with this specific drug delivery system (DDS) to analyze its physical and spectral properties. Background Data: It has been suggested in the literature that BChl-a is a potential sensitizer in photodynamic tumor therapy and until now has only been investigated in organic media. Methods: Nanoparticles loaded with the photosensitizer BChl-a were prepared by the solvent evaporation technique. Parameters such as particle size, drug encapsulation efficiency, external morphology, and in vitro release behavior were evaluated. The photophysical properties (absorption, fluorescence, fluorescence quantum yields, and singlet oxygen quantum yields) of BChl-a, were investigated in toluene and when encapsulated in nanoparticles. Results: Scanning electron microscopy and dynamic light scattering revealed that particles loaded with BChl-a are spherical in shape, and they have a diameter of 660 nm and a low tendency to aggregate. The encapsulation efficiency obtained in this procedure was 69%. Spectroscopic analysis showed an absorption band centered at 782 nm in nanoparticles used as a DDS. Fluorescence quantum yield (F ؍ 0.19) and higher efficiency in singlet oxygen production (⌽ ⌬ ؍ 0.26) was also observed. Conclusions: The results suggest that this DDS is potentially useful for the delivery and release of BChl-a as a photosensitizer in photodynamic therapy (PDT) protocols due to its excellent biodegradability, biocompatibility, and maintenance of its spectroscopic properties when compared with other dyes in homogenous media. The biocompatible DDS medium is a new proposal and will make feasible the use of BChl-a as a dye for PDT, improving the utilization of non-organic media to deliver this kind of molecule.
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...
Poly (D,L-lactide-co-glycolide) nanoparticles:Uptake by epithelial cells and cytotoxicity
Nanoparticles as drug delivery systems offer benefits such as protection of the encapsulated drug against degradation, site-specific targeting and prolonged blood circulation times. The aim of this study was to investigate nanoparticle uptake into Caco-2 cell monolayers, their co-localization within the lysosomal compartment and their cytotoxicity in different cell lines. Rhodamine-6G labelled poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles were prepared by a double emulsion solvent evaporation freeze-drying method. Uptake and co-localisation of PLGA nanoparticles in lysosomes were visualized by confocal laser scanning microscopy. The cytotoxicity of the nanoparticles was evaluated on different mammalian cells lines by means of Trypan blue exclusion and the MTS assay. The PLGA nanoparticles accumulated in the intercellular spaces of Caco-2 cell monolayers, but were also taken up transcellularly into the Caco-2 cells and partially co-localized within the lysosomal compartment indicating involvement of endocytosis during uptake. PLGA nanoparticles did not show cytotoxic effects in all three cell lines. Intact PLGA nanoparticles are therefore capable of moving across epithelial cell membranes partly by means of endocytosis without causing cytotoxic effects. Keywords: biocompatible polymers, Caco-2 cells, cellular uptake, cytotoxicity, PLGA nanoparticles