Poly(lactic acid)
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Poly(lactic-co-glycolic acid) (PLGA) is a US Food and Drug Administration (FDA)-approved polymer used in humans in the forms of resorbable sutures, drug carriers, and bone regeneration materials. Recently, PLGA-based conjugates have been extensively investigated for cancer, which is the second leading cause of death globally. This article presents an account of the literature on PLGA-based conjugates, focusing on their chemistries, biological activity, and functions as targeted drug carriers or sustained drug controllers for common cancers (e.g., breast, prostate, and lung cancers). The preparation and drug encapsulation of PLGA nanoparticles and folate-decorated poly(ethylene glycol)-poly(lactic-co-glycolic acid) (FA-PEG-PLGA) conjugates are discussed, along with several representative examples. Particularly, the reactions used for preparing drug-conjugated PLGA and FA-PEG-PLGA are emphasized, with the associated chemistries involved in the formation of structures and their biocompatibility with internal organs. This review provides a deeper understanding of the constituents and interactions of PLGA-conjugated materials to ensure successful conjugation in PLGA material design and the subsequent biomedical applications.
- MeSH
- kopolymer kyseliny glykolové a mléčné MeSH
- kyselina listová chemie MeSH
- lidé MeSH
- nádory * MeSH
- nanočástice * chemie MeSH
- nosiče léků chemie MeSH
- polyethylenglykoly chemie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Geografické názvy
- Spojené státy americké MeSH
Prediction of poly(lactic-co-glycolic acid) (PLGA) micro- and nanoparticles' dissolution rates plays a significant role in pharmaceutical and medical industries. The prediction of PLGA dissolution rate is crucial for drug manufacturing. Therefore, a model that predicts the PLGA dissolution rate could be beneficial. PLGA dissolution is influenced by numerous factors (features), and counting the known features leads to a dataset with 300 features. This large number of features and high redundancy within the dataset makes the prediction task very difficult and inaccurate. In this study, dimensionality reduction techniques were applied in order to simplify the task and eliminate irrelevant and redundant features. A heterogeneous pool of several regression algorithms were independently tested and evaluated. In addition, several ensemble methods were tested in order to improve the accuracy of prediction. The empirical results revealed that the proposed evolutionary weighted ensemble method offered the lowest margin of error and significantly outperformed the individual algorithms and the other ensemble techniques.
The aim of this study was to fabricate novel microparticles (MPs) for efficient and long-term delivery of amikacin (AMI). The emulsification method proposed for encapsulating AMI employed low-molecular-weight poly(lactic acid) (PLA) and poly(lactic acid-co-polyethylene glycol) (PLA-PEG), both supplemented with poly(vinyl alcohol) (PVA). The diameters of the particles obtained were determined as less than 30 μm. Based on an in-vitro release study, it was proven that the MPs (both PLA/PVA- and PLA-PEG/PVA-based) demonstrated long-term AMI release (2 months), the kinetics of which adhered to the Korsmeyer-Peppas model. The loading efficiencies of AMI in the study were determined at the followings levels: 36.5 ± 1.5 μg/mg for the PLA-based MPs and 106 ± 32 μg/mg for the PLA-PEG-based MPs. These values were relatively high and draw parallels with studies published on the encapsulation of aminoglycosides. The MPs provided antimicrobial action against the Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae bacterial strains. The materials were also comprehensively characterized by the following methods: differential scanning calorimetry; gel permeation chromatography; scanning electron microscopy; Fourier transform infrared spectroscopy-attenuated total reflectance; energy-dispersive X-ray fluorescence; and Brunauer-Emmett-Teller surface area analysis. The findings of this study contribute toward discerning new means for conducting targeted therapy with polar, broad spectrum antibiotics.
- MeSH
- amikacin aplikace a dávkování chemie MeSH
- antibakteriální látky aplikace a dávkování chemie MeSH
- Escherichia coli účinky léků MeSH
- Klebsiella pneumoniae účinky léků MeSH
- laktáty chemie MeSH
- mikrobiální testy citlivosti MeSH
- molekulová hmotnost MeSH
- nosiče léků chemie MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemie MeSH
- polyvinylalkohol chemie MeSH
- příprava léků metody MeSH
- Pseudomonas aeruginosa účinky léků MeSH
- rozpustnost MeSH
- Staphylococcus aureus účinky léků MeSH
- tobolky MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The biodegradation of four poly(l-lactic acid) (PLA) samples with molecular weights (MW) ranging from approximately 34 to 160kgmol(-1) was investigated under composting conditions. The biodegradation rate decreased, and initial retardation was discernible in parallel with the increasing MW of the polymer. Furthermore, the specific surface area of the polymer sample was identified as the important factor accelerating biodegradation. Microbial community compositions and dynamics during the biodegradation of different PLA were monitored by temperature gradient gel electrophoresis, and were found to be virtually identical for all PLA materials and independent of MW. A specific PLA degrading bacteria was isolated and tentatively designated Thermopolyspora flexuosa FTPLA. The addition of a limited amount of low MW PLA did not accelerate the biodegradation of high MW PLA, suggesting that the process is not limited to the number of specific degraders and/or the induction of specific enzymes. In parallel, abiotic hydrolysis was investigated for the same set of samples and their courses found to be quasi-identical with the biodegradation of all four PLA samples investigated. This suggests that the abiotic hydrolysis represented a rate limiting step in the biodegradation process and the organisms present were not able to accelerate depolymerization significantly by the action of their enzymes.
Commercially available antibacterial semisolid preparations intended for topical application provide only short-term drug release. A sustained kinetics is possible by exploitation of a biodegradable polymer carrier. The purpose of this work is to formulate a mucoadhesive system with aciclovir (ACV) based on a solid molecular dispersion of this drug in poly(lactic-co-glycolic acid) branched on tripenterythritol (PLGA/T). The ACV incorporation into PLGA/T was carried out either by solvent method, or melting method, or plasticization method using various plasticizers. The drug-polymer miscibility, plasticizer efficiency and content of residual solvent were found out employing DSC. Viscosity was measured at the shear rate range from 0.10 to 10.00 s(-1) at three temperatures and data were analyzed by Newtonian model. The mucoadhesive properties were ascertained in the tensile test on a mucin substrate. The amount of ACV released was carried out in a wash-off dissolution test. The DSC results indicate a transformation of crystalline form of ACV into an amorphous dissolved in branched polyester carrier, and absence of methyl formate residuals in formulation. All the tested plasticizers are efficient at Tg depression and viscosity decrease. The non-conventional ethyl pyruvate possessing supportive anti-inflammatory activity was evaluated as the most suitable plasticizer. The ACV release was strongly dependent on the ethyl pyruvate concentration and lasted from 1 to 10 days. The formulated PLGA/T system with ACV exhibits increased adhesion to mucosal hydrophilic surfaces and prolonged ACV release controllable by degradation process and viscosity parameters.
- MeSH
- acyklovir aplikace a dávkování chemie MeSH
- biokompatibilní materiály chemie MeSH
- časové faktory MeSH
- hydrofobní a hydrofilní interakce MeSH
- kyselina mléčná chemie MeSH
- kyselina polyglykolová chemie MeSH
- léky s prodlouženým účinkem MeSH
- povrchové vlastnosti MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- změkčovadla aplikace a dávkování chemie MeSH
- Publikační typ
- časopisecké články MeSH
The preemergence chloroacetamide herbicide metazachlor was encapsulated in biodegradable low molecular weight poly(lactic acid) micro- and submicroparticles, and its release to the water environment was investigated. Three series of particles, S, M, and L, varying in their size (from 0.6 to 8 μm) and with various initial amounts of the active agent (5%, 10%, 20%, 30% w/w) were prepared by the oil-in-water solvent evaporation technique with gelatin as biodegradable surfactant. The encapsulation efficiencies reached were about 60% and appeared to be lower for smaller particles. Generally, it was found that the rate of herbicide release decreased with increasing size of particles. After 30 days the portions of the herbicide released for its highest loading (30% w/w) were 92%, 56%, and 34% for about 0.6, 0.8, and 8 μm particles, respectively. The release rates were also lower for lower herbicide loadings. Metazachlor release from larger particles tended to be a diffusion-controlled process, while for smaller particles the kinetics was strongly influenced by an initial burst release.
- MeSH
- acetamidy chemie MeSH
- herbicidy chemie MeSH
- kinetika MeSH
- kyselina mléčná chemie MeSH
- léky s prodlouženým účinkem chemie MeSH
- molekulová hmotnost MeSH
- polymery chemie MeSH
- příprava léků metody MeSH
- velikost částic MeSH
- Publikační typ
- časopisecké články MeSH
- hodnotící studie MeSH
- práce podpořená grantem MeSH
Biocompatible polymers derived from ? -hydroxyacids, in particular homopolymers and copolymers of lactic and glycolic acids, are widely used in surgery, tissue engineering and drug formulation. Their polycondensation with polyhydric alcohols yields degradable low-molecularweight branched oligoesters. Polymer plasticizers improve processibility, decrease brittleness and impart mechanical endurance to the oligoesters. Out of many plasticizers used in polymers, only a few of them have been approved for pharmaceutical applications. The type and amount of plasticizers influence the degradation time of polymers and thus the drug release. Biodegradable polyesters are currently used in parenteral drug delivery as solid implants, microparticles and in-situ implants. Homopolymers and copolymers of lactic and glycolic acids are suitable drug carriers for the purpose in treatment of cancer, drug addiction, contraception and vaccination as well as for the controlled release of growth factors in tissue engineering.
Poly(lactic acid)-block-poly(oxirane)s (PLA-b-POE) of various compositions were prepared using a one-pot approach and then extended in a reaction with l-lysine diethyl ester diisocyanate, thereby forming polyester-ether-urethanes (PEU) with prolonged chains and units with increased degradability. The PEUs are processed by electrospinning to prepare degradable nanofibrous sheet materials with and without encapsulating the antibiotic Vancomycin (VAC). PLA block isomerism and POE blocks oligomeric content (1000 g/mol) affect the thermal properties, processability, nanofibrous sheet morphology, abiotic degradation, cytocompatibility, and encapsulated antibiotic release rate of prepared PEUs. Therefore, our findings provide an effective approach to tuning the functional properties of these advanced biocompatible materials. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 2378-2387, 2019.
- MeSH
- antibakteriální látky * chemie farmakologie MeSH
- buňky NIH 3T3 MeSH
- lékové transportní systémy * MeSH
- myši MeSH
- nanovlákna chemie MeSH
- polyestery chemie farmakologie MeSH
- polyethylenglykoly chemie farmakologie MeSH
- polyurethany chemie farmakologie MeSH
- testování materiálů * MeSH
- vankomycin * chemie farmakologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The objective of the study was to design, synthetize and characterize poly(lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) with entrapped fish oil (FO) for possible application in a cutaneous wound healing. Morphology of NPs was evaluated by transmission electron microscopy. Antimicrobial characteristics were tested using the disk diffusion method and plate count method, and cytotoxicity was evaluated by the MTT assay. Fish oil (y) was released from PLGA NPs within the time interval (x) of 96 h according to equation y = 6.2 + 0.914x. PLGA-FO NPs did not affect growth of Staphylococcus aureus or methicillin-resistant S. aureus (MRSA) strains. No cytotoxic effect of the tested NPs on the keratinocyte cell line was observed for concentration of 1 μg/ml. PLGA-FO NPs represent an interesting alternative for wound healing due to an excellent biocompatibility and unique release profile of FO, despite their lack of antimicrobial efficiency.
An innovative microcarrier based on a carboxy-enriched and branched polylactic acid derivative was developed to enhance the in vitro phototoxicity of the photosensitizer and prodrug 5-aminolevulinic. Microparticles, prepared by double emulsion technique and loaded with the prodrug were carefully characterized and the effect of the polymer structure on the chemical, physical and biological properties of the final product was evaluated. Results showed that microparticles have a spherical shape and ability to allocate up to 30 μg of the photosensitizer per mg of carrier despite their difference in solubility. Release studies performed in various simulated physiological conditions demonstrate the influence of the branched structure and the presence of the additional carboxylic groups on the release rate and the possibility to modulate it. In vitro assays conducted on human epithelial adenocarcinoma cells proved the not cytotoxicity of the carriers in a wide range of concentrations. The hemocompatibility and surface proteins adsorption were evaluated at different microparticles concentrations to evaluate the safety and estimate the possible microparticles residential time in the bloodstream. The advantages, of loading 5-aminolevulinic acid in the prepared carrier has been deeply described in terms of enhanced phototoxicity, compared to the free 5-aminolevulinic acid formulation after irradiation with light at 635 nm. The obtained results demonstrate the advantages of the prepared derivative compared to the linear polylactide for future application in photodynamic therapy based on the photosensitizer 5-aminolevulinic acid.
- MeSH
- erytrocyty cytologie účinky léků metabolismus MeSH
- fotosenzibilizující látky chemie toxicita MeSH
- HeLa buňky MeSH
- hemolýza účinky léků MeSH
- koncentrace vodíkových iontů MeSH
- kyselina aminolevulová chemie metabolismus toxicita MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nosiče léků chemie MeSH
- polyestery chemie MeSH
- rozpustnost MeSH
- světlo MeSH
- uvolňování léčiv MeSH
- viabilita buněk účinky léků MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
