poly(L-lactic acid)
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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.
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.
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
Due to their unique properties, such as controlled drug release and improved bioavailability, polymeric microparticles and nanoparticles (MPs and NPs) have gained considerable interest in the pharmaceutical industry. Nevertheless, the high costs associated with biodegradable polymers and the active pharmaceutical ingredients (APIs) used for treating serious diseases, coupled with the vast number of API-polymer combinations, make the search for effective API-polymer MPs and NPs a costly and time-consuming process. In this work, the correlation between the compatibility of selected model APIs (i.e., ibuprofen, naproxen, paracetamol, and indomethacin) with poly(lactide-co-glycolide) (PLGA) derived from respective binary phase diagrams and characteristics of prepared MPs and NPs, such as the drug loading and solid-state properties, was investigated to probe the possibility of implementing the modeling of API-polymer thermodynamic and kinetic phase behavior as part of rational design of drug delivery systems based on MPs and NPs. API-PLGA-based MPs and NPs were formulated using an emulsion-solvent evaporation technique and were characterized for morphology, mean size, zeta potential, drug loading, and encapsulation efficiency. The solid-state properties of the encapsulated APIs were assessed using differential scanning calorimetry and X-ray powder diffraction. The evaluated compatibility was poor for all considered API-PLGA pairs, which is in alignment with the experimental results showing low drug loading in terms of amorphous API content. At the same time, drug loading of the studied APIs in terms of amorphous content was found to follow the same trend as their solubility in PLGA, indicating a clear correlation between API solubility in PLGA and achievable drug loading. These findings suggest that API-polymer phase behavior modeling and compatibility screening can be employed as an effective preformulation tool to estimate optimum initial API concentration for MP and NP preparation or, from a broader perspective, to tune or select polymeric carriers offering desired drug loading.
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
PURPOSE: The present study aims to prepare poly(D,L-lactic acid) (PLA) nanofibers loaded by the immunosuppressant cyclosporine A (CsA, 10 wt%). Amphiphilic poly(ethylene glycol)s (PEG) additives were used to modify the hydrophobic drug release kinetics. METHODS: Four types of CsA-loaded PLA nanofibrous carriers varying in the presence and molecular weight (MW) of PEG (6, 20 and 35 kDa) were prepared by needleless electrospinning. The samples were extracted for 144 h in phosphate buffer saline or tissue culture medium. A newly developed and validated LC-MS/MS method was utilized to quantify the amount of released CsA from the carriers. In vitro cell experiments were used to evaluate biological activity. RESULTS: Nanofibers containing 15 wt% of PEG showed improved drug release characteristics; significantly higher release rates were achieved in initial part of experiment (24 h). The highest released doses of CsA were obtained from the nanofibers with PEG of the lowest MW (6 kDa). In vitro experiments on ConA-stimulated spleen cells revealed the biological activity of the released CsA for the whole study period of 144 h and nanofibers containing PEG with the lowest MW exhibited the highest impact (inhibition). CONCLUSIONS: The addition of PEG of a particular MW enables to control CsA release from PLA nanofibrous carriers. The biological activity of CsA-loaded PLA nanofibers with PEG persists even after 144 h of previous extraction. Prepared materials are promising for local immunosuppression in various medical applications.
- MeSH
- buněčné linie MeSH
- cyklosporin aplikace a dávkování chemie MeSH
- hydrofobní a hydrofilní interakce MeSH
- imunosupresiva aplikace a dávkování chemie MeSH
- kinetika MeSH
- kultivační média MeSH
- lidé MeSH
- nanovlákna chemie MeSH
- nosiče léků MeSH
- polyestery chemie MeSH
- polyethylenglykoly chemie MeSH
- povrchové vlastnosti MeSH
- slezina cytologie MeSH
- techniky tkáňových kultur MeSH
- uvolňování léčiv MeSH
- velikost částic MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Despite several shortcomings such as extreme hydrophobicity, low drug capacity, characteristic triphasic drug release pattern with a high burst effect, poly(lactic-co-glycolic acid derivatives are widely used in drug delivery. Most frequent attempts to improve their properties are blending with other polymers or synthesis of block copolymers. We introduce a new class of branched poly(lactic-co-glycolic acid) derivatives as promising biodegradable carriers for prolonged or targeted drug release systems, employed as thin adhesive films, solid dispersions, in situ forming implants or nanoparticles. A series of poly(lactic-co-glycolic acid) derivatives with lower molar mass and star or comb architecture were synthesized by a simple, catalyst free, direct melt polycondensation method not requiring purification of the obtained sterile product by precipitation. Branching monomers used were mannitol, pentaerythritol, dipentaerythritol, tripentaerythritol and polyacrylic acid. The products were characterized by molar mass averages, average branching ratio, rheological and thermal properties.
