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.

• Klíčová slova
• Active pharmaceutical ingredient, Compatibility, Drug delivery system, Micro/nano-particle, Phase diagram, Poly(lactide-co-glycolide),
• MeSH
• kopolymer kyseliny glykolové a mléčné chemie   MeSH
• léčivé přípravky MeSH
• lékové transportní systémy metody   MeSH
• nanočástice * chemie   MeSH
• nosiče léků chemie   MeSH
• polymery * chemie   MeSH
• velikost částic MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dilactide MeSH Prohlížeč
• kopolymer kyseliny glykolové a mléčné MeSH
• léčivé přípravky MeSH
• nosiče léků MeSH
• polymery * MeSH

Poly-(lactide-co-glycolide) (PLGA) is an FDA-approved biodegradable polymer which has been widely used as a scaffold for tissue engineering applications. Collagen has been used as a coating material for bone contact materials, but relatively little interest has focused on biomimetic coating of PLGA with extracellular matrix components such as collagen and the glycosaminoglycan chondroitin sulfate (CS). In this study, PLGA films were coated with collagen type I or collagen I with CS (collagen I/CS) to investigate the effect of CS on the behaviour of the osteoblastic cell line MG 63. Collagen I/CS coatings promoted a significant increase in cell number after 3 days (in comparison to PLGA) and after 7 days (in comparison to PLGA and collagen-coated PLGA). No influence of collagen I or collagen I/CS coatings on the spreading area after 1 day of culture was observed. However, the cells on collagen I/CS formed numerous filopodia and displayed well developed vinculin-containing focal adhesion plaques. Moreover, these cells contained a significantly higher concentration of osteocalcin, measured per mg of protein, than the cells on the pure collagen coating. Thus, it can be concluded that collagen I/CS coatings promote MG 63 cell proliferation, improve cell adhesion and enhance osteogenic cell differentiation.

• MeSH
• biokompatibilní potahované materiály chemie   farmakologie   MeSH
• buněčné inženýrství metody   MeSH
• buněčné linie MeSH
• chondroitinsulfáty chemie   farmakologie   MeSH
• kolagen typu I chemie   farmakologie   MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kultivované buňky MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• lidé MeSH
• osteoblasty cytologie   účinky léků   fyziologie   MeSH
• osteogeneze účinky léků   fyziologie   MeSH
• proliferace buněk účinky léků   MeSH
• testování materiálů MeSH
• tkáňové podpůrné struktury MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biokompatibilní potahované materiály MeSH
• chondroitinsulfáty MeSH
• kolagen typu I MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH

BACKGROUND: Nanofibrous scaffolds loaded with bioactive nanoparticles are promising materials for bone tissue engineering. METHODS: In this study, composite nanofibrous membranes containing a copolymer of L-lactide and glycolide (PLGA) and diamond nanoparticles were fabricated by an electrospinning technique. PLGA was dissolved in a mixture of methylene chloride and dimethyl formamide (2:3) at a concentration of 2.3 wt%, and nanodiamond (ND) powder was added at a concentration of 0.7 wt% (about 23 wt% in dry PLGA). RESULTS: In the composite scaffolds, the ND particles were either arranged like beads in the central part of the fibers or formed clusters protruding from the fibers. In the PLGA-ND membranes, the fibers were thicker (diameter 270 ± 9 nm) than in pure PLGA meshes (diameter 218 ± 4 nm), but the areas of pores among these fibers were smaller than in pure PLGA samples (0.46 ± 0.02 μm(2) versus 1.28 ± 0.09 μm(2) in pure PLGA samples). The PLGA-ND membranes showed higher mechanical resistance, as demonstrated by rupture tests of load and deflection of rupture probe at failure. Both types of membranes enabled the attachment, spreading, and subsequent proliferation of human osteoblast-like MG-63 cells to a similar extent, although these values were usually lower than on polystyrene dishes. Nevertheless, the cells on both types of membranes were polygonal or spindle-like in shape, and were distributed homogeneously on the samples. From days 1-7 after seeding, their number rose continuously, and at the end of the experiment, these cells were able to create a confluent layer. At the same time, the cell viability, evaluated by a LIVE/DEAD viability/cytotoxicity kit, ranged from 92% to 97% on both types of membranes. In addition, on PLGA-ND membranes, the cells formed well developed talin-containing focal adhesion plaques. As estimated by the determination of tumor necrosis factor-alpha levels in the culture medium and concentration of intercellular adhesion molecule-1, MG-63 cells, and RAW 264.7 macrophages on these membranes did not show considerable inflammatory activity. CONCLUSION: This study shows that nanofibrous PLGA membranes loaded with diamond nanoparticles have interesting potential for use in bone tissue engineering.

• Klíčová slova
• electrospinning, human bone cells, nanofibers, nanoparticles, nanotechnology, regenerative medicine,
• MeSH
• buněčná adheze MeSH
• buněčné linie MeSH
• diamant chemie   MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kostní náhrady chemie   MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• lidé MeSH
• mikrofilamenta metabolismus   MeSH
• mikroskopie elektronová rastrovací MeSH
• myši MeSH
• nanočástice chemie   ultrastruktura   MeSH
• nanomedicína MeSH
• nanovlákna chemie   ultrastruktura   MeSH
• osteoblasty cytologie   imunologie   fyziologie   MeSH
• proliferace buněk MeSH
• testování materiálů MeSH
• tkáňové inženýrství metody   MeSH
• tkáňové podpůrné struktury chemie   MeSH
• transmisní elektronová mikroskopie MeSH
• viabilita buněk MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• diamant MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kostní náhrady MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH

The particle size (PS) and encapsulation efficiency (EE%) of drug-loaded nanoparticles (NPs) may inhibit their cellular uptake and lead to possible leakage of the drug into the systemic circulation at the tumor site. In this work, ultra-high paclitaxel-loaded poly(lactide-co-glycolide) NPs (PTX-PLGA-NPs) with ultra-small sizes were prepared and optimized by adopting the principles of quality by design (QbD) approach. The optimized PTX-PLGA-NPs showed ultra-small spherical particles of about 53 nm with EE% exceeding 90%, a relatively low polydispersity index (PDI) of 0.221, an effective surface charge of -10.1 mV, and a 10-fold increase in the in vitro drug release over 72 h relative to free drug. The cellular viability of pharynx carcinoma cells decreased by almost 50% in 24 h following treatment with optimized PTX-PLGA-NPs, compared to only 20% from the free drug. The intracellular uptake of PTX-PLGA-NPs was highly favored, and the antitumor activity of PTX was remarkably improved with a reduction in its half maximal inhibitory concentration (IC50), by almost 50% relative to free drug solution. These results suggest that the optimal critical formulation parameters, guided by QbD principles, could produce PLGA-NPs with remarkably high EE% and ultra-small PS, resulting in enhanced cellular uptake and efficacy of PTX.

• Klíčová slova
• head and neck cancer, nanoparticles, paclitaxel, poly(lactide-co-glycolide), quality-by-design,
• Publikační typ
• časopisecké články MeSH

Recent complications on the use of polypropylene meshes for hernia repair has led to the development of meshes or films, which were based on resorbable polymers such as polycaprolactone (PCL), polylactic acid (PLA) and poly(lactic-co-glycolic acid) (PLGA). These materials are able to create suitable bioactive environment for the growth and development of cells. In this research, we mainly focused on the relations among structure, mechanical performance and biocompatiblity of PCL/PLA and PCL/PLGA and blends prepared by solution casting. The films were characterized regarding the chemical structure, morphology, physicochemical properties, cytotoxicity, biocompatibility and cell growth. All the films showed high tensile strength ranging from 9.5 to 11.8 MPa. SAXS showed that the lamellar stack structure typical for PCL was present even in the blend films while the morphological parameters of the stacks varied slightly with the content of PLGA or PLA in the blends. WAXS indicated preferential orientation of crystallites (and thus, also the lamellar stacks) in the blend films. In vitro studies revealed that PCL/PLGA films displayed better cell adhesion, spreading and proliferation than PCL/PLA and PCL films. Further the effect of blending on the degradation was investigated, to understand the significant variable within the process that could provide further control of cell adhesion. The results showed that the investigated blend films are promising materials for biomedical applications.

• Klíčová slova
• Biocompatibility, Mechanical properties, Nanoscale morphology, Polycaprolactone, Resorbable blends,
• MeSH
• difrakce rentgenového záření MeSH
• glykoly * MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• maloúhlový rozptyl MeSH
• polyestery MeSH
• vstřebatelné implantáty * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glykoly * MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• poly(lactide) MeSH Prohlížeč
• polycaprolactone MeSH Prohlížeč
• polyestery MeSH

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
• Názvy látek
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina listová MeSH
• nosiče léků MeSH
• polyethylenglykoly MeSH

Many anticancer active pharmaceutical ingredients (APIs), such as paclitaxel (PTX), exhibit poor water solubility, which limits their bioavailability and necessitates the use of excipients. While biodegradable polymeric excipients combined with nanotechnology offer promising solutions, the high cost of polymers and APIs, along with the vast number of potential API-polymer combinations, poses significant challenges in developing effective drug delivery systems (DDS). This study explores the potential of API-polymer phase behavior modeling as part of the design of nanoparticle (NP)-based DDS for PTX using poly(lactide-co-glycolide) (PLGA) and poly(lactide-co-glycolide)-b-poly(ethylene glycol) (PLGA-PEG) with varying molecular weights. The phase behavior of PTX-PLGA/PLGA-PEG systems, which reflects the compatibility of PTX with polymeric excipients, was predicted using the Conductor-like Screening Model for Real Solvents (COSMO-RS). To investigate the correlation between the predictions and experimental observations, PTX-PLGA and PEGylated PLGA NPs were prepared via an emulsion-solvent evaporation method with varying initial PTX amounts. The predicted trends in PTX solubility in polymeric excipients were then compared with key NP characteristics, such as drug loading, solid-state properties, and cytotoxicity in HeLa, SKOV-3, and MRC-5 cells. COSMO-RS predictions indicated limited PTX solubility in PLGA, which aligns with experimental observations, where the maximum amorphous PTX loading did not exceed 2 wt%, regardless of the polymer molecular weight. COSMO-RS modeling predicted higher compatibility of PTX with PEG, suggesting that incorporating PEG would enhance PTX loading in PEGylated NPs. This trend was corroborated by experimental findings, which showed increased drug loading capacity and slower PTX release from PEGylated NPs during cytotoxicity studies. These results highlight the potential of API-polymer modeling as a tool for tailoring polymeric carriers and optimizing API consumption in NP-based DDS development.

• Klíčová slova
• COSMO-RS, Cell tests, Compatibility, Drug delivery systems, Nanoparticles, PLGA copolymers, Paclitaxel,
• MeSH
• fytogenní protinádorové látky * chemie   aplikace a dávkování   farmakologie   MeSH
• kopolymer kyseliny glykolové a mléčné * chemie   MeSH
• lékové transportní systémy MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nanočástice * chemie   aplikace a dávkování   MeSH
• nosiče léků * chemie   MeSH
• paclitaxel * chemie   aplikace a dávkování   farmakologie   MeSH
• polyethylenglykoly chemie   MeSH
• polyglactin 910 * chemie   MeSH
• pomocné látky chemie   MeSH
• rozpustnost MeSH
• uvolňování léčiv MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fytogenní protinádorové látky * MeSH
• kopolymer kyseliny glykolové a mléčné * MeSH
• nosiče léků * MeSH
• paclitaxel * MeSH
• polyethylenglykoly MeSH
• polyglactin 910 * MeSH
• pomocné látky 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.

• Klíčová slova
• ensemble, feature selection, protein dissolution, regression models,
• MeSH
• algoritmy MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná chemie   MeSH
• kyselina polyglykolová chemie   MeSH
• mikrosféry MeSH
• nanočástice chemie   MeSH
• rozpustnost MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH

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.

• Klíčová slova
• Acyclovir, branched molecule, drug release, ethyl pyruvate, mucoadhesivity, plasticization, poly(lactic-co-glycolic acid), solid dispersion,
• MeSH
• acyklovir aplikace a dávkování   chemie   MeSH
• biokompatibilní materiály chemie   MeSH
• časové faktory MeSH
• hydrofobní a hydrofilní interakce MeSH
• kopolymer kyseliny glykolové a mléčné 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
• Názvy látek
• acyklovir MeSH
• biokompatibilní materiály MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• kyselina mléčná MeSH
• kyselina polyglykolová MeSH
• léky s prodlouženým účinkem MeSH
• změkčovadla MeSH

Anti-CD133 monoclonal antibody (Ab)-conjugated poly(lactide-co-glycolide) (PLGA) nanocarriers, for the targeted delivery of oxaliplatin (OXA) and superparamagnetic nanoparticles (IO-OA) to colorectal cancer cells (CaCo-2), were designed, synthesized, characterized, and evaluated in this study. The co-encapsulation of OXA and IO-OA was achieved in two types of polymeric carriers, namely, PLGA and poly(lactide-co-glycolide)-poly(ethylene glycol) (PLGA-PEG) by double emulsion. PLGA_IO-OA_OXA and PEGylated PLGA_IO-OA_OXA nanoparticles displayed a comparable mean diameter of 207 ± 70 nm and 185 ± 119 nm, respectively. The concentration of the released OXA from the PEGylated PLGA_IO-OA_OXA increased very rapidly, reaching ~100% release after only 2 h, while the PLGA_IO-OA_OXA displayed a slower and sustained drug release. Therefore, for a controlled OXA release, non-PEGylated PLGA nanoparticles were more convenient. Interestingly, preservation of the superparamagnetic behavior of the IO-OA, without magnetic hysteresis all along the dissolution process, was observed. The non-PEGylated nanoparticles (PLGA_OXA, PLGA_IO-OA_OXA) were selected for the anti-CD133 Ab conjugation. The affinity of Ab-coated nanoparticles for CD133-positive cells was examined using fluorescence microscopy in CaCo-2 cells, which was followed by a viability assay.

• Klíčová slova
• PLGA nanoparticles, antibody, colorectal cancer, drug delivery, iron oxide nanoparticles, oxaliplatin, targeted delivery,
• MeSH
• antigen AC133 imunologie   MeSH
• imunokonjugáty farmakologie   MeSH
• kolorektální nádory farmakoterapie   imunologie   patologie   MeSH
• kopolymer kyseliny glykolové a mléčné chemie   MeSH
• lékové transportní systémy * MeSH
• lidé MeSH
• monoklonální protilátky chemie   MeSH
• nanočástice aplikace a dávkování   chemie   MeSH
• nosiče léků chemie   MeSH
• oxaliplatin chemie   MeSH
• protinádorové látky chemie   MeSH
• uvolňování léčiv MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antigen AC133 MeSH
• imunokonjugáty MeSH
• kopolymer kyseliny glykolové a mléčné MeSH
• monoklonální protilátky MeSH
• nosiče léků MeSH
• oxaliplatin MeSH
• PROM1 protein, human MeSH Prohlížeč
• protinádorové látky MeSH