Micro- and nanostructures prepared from biodegradable homopolymers and amphiphilic block copolymers (AmBCs) have found application as drug-delivery systems (DDSs). The ability to accumulate a drug is a very important parameter characterizing a given DDS. This work focuses on the impact of DDS size, the packing of polymer chains in the DDS, and drug - polymer matrix compatibility on the hydrophobic drug - loading capacity (DLC) of nano/microcarriers prepared from a biodegradable polymer or its copolymer. Using experimental measurements in combination with atomistic molecular dynamics simulations, an analysis of curcumin encapsulation in microspheres (MSs) from polylactide (PLA) homopolymer and nanoparticles (NPs) from PLA-block-poly(2-methacryloyloxyethylphosphorylcholine) AmBC was performed. The results show that curcumin has good affinity for the PLA matrix due to its hydrophobic nature. However, the DLC value is limited by the fact that curcumin only accumulates in the peripheral part of these structures. Such uneven drug distribution in the PLA matrix results from the non-homogeneous density of MSs (non-uniform packing of the polymer chains in the coil). The results also indicate that the MSs can retain a greater amount of hydrophobic drug compared to the NPs, which is associated with the formation of drug aggregates inside the PLA microparticles.
Various types of nanofibers are increasingly used in tissue engineering, mainly for their ability to mimic the architecture of tissue at the nanoscale. We evaluated the adhesion, growth, viability, and differentiation of human osteoblast-like MG 63 cells on polylactide (PLA) nanofibers prepared by needle-less electrospinning and loaded with 5 or 15 wt % of hydroxyapatite (HA) nanoparticles. On day 7 after seeding, the cell number was the highest on samples with 15 wt % of HA. This result was confirmed by the XTT test, especially after dynamic cultivation, when the number of metabolically active cells on these samples was even higher than on control polystyrene. Staining with a live/dead kit showed that the viability of cells on all nanofibrous scaffolds was very high and comparable to that on control polystyrene dishes. An enzyme-linked immunosorbent assay revealed that the concentration of osteocalcin was also higher in cells on samples with 15 wt % of HA. There was no immune activation of cells (measured by production of TNF-alpha), associated with the incorporation of HA. Moreover, the addition of HA suppressed the creep behavior of the scaffolds in their dry state. Thus, nanofibrous PLA scaffolds have potential for bone tissue engineering, particularly those with 15 wt % of HA.
- MeSH
- Cell Adhesion MeSH
- Cell Differentiation * MeSH
- Cell Line MeSH
- Durapatite chemistry MeSH
- Bone Substitutes MeSH
- Humans MeSH
- Nanofibers chemistry MeSH
- Osteoblasts cytology metabolism MeSH
- Osteocalcin biosynthesis MeSH
- Polyesters chemistry MeSH
- Tissue Engineering methods MeSH
- Cell Survival MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
The aim of this work was to investigate the potential of an amphiphilic system comprising chitosan-grafted polylactide and carboxyl-functionalized polylactide acid as a carrier for the controlled release and co-release of two DNA alkylating drugs: doxorubicin and temozolomide. Polylactide and carboxyl-functionalized polylactide acid were obtained through direct melt polycondensation reaction, using methanesulfonic acid as a non-toxic initiator, and subsequently these were grafted to the chitosan backbone through a coupling reaction, utilizing 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as a condensing agent. ATR-FTIR analysis and conductometric titration confirmed that a reaction between CS and PLA, PLACA2% and PLACA5% occurred. Chitosan-grafted-polylactide and polylactide-citric acid nanoparticles were prepared via the polyelectrolyte complex technique, applying dextran sulphate as a polyanion, and loaded with doxorubicin and temozolomide. The diameter of particles, ζ-potential and their relationship to temperature and pH were analysed in all formulations. Encapsulation, co-encapsulation efficiency and release studies were conducted in different physiological simulated environments and human serum. Results showed the continuous release of drugs without an initial burst in different physiological media.
- MeSH
- Chitosan administration & dosage chemistry MeSH
- Dacarbazine administration & dosage analogs & derivatives chemistry therapeutic use MeSH
- Doxorubicin administration & dosage chemistry therapeutic use MeSH
- Lactic Acid administration & dosage chemical synthesis chemistry MeSH
- Drug Delivery Systems * MeSH
- Humans MeSH
- Molecular Structure MeSH
- Nanoparticles administration & dosage chemistry MeSH
- Polymers administration & dosage chemical synthesis chemistry MeSH
- Surface-Active Agents administration & dosage chemistry MeSH
- Surface Properties MeSH
- Temperature MeSH
- Particle Size MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
V rámci této experimentální studie byly připraveny biodegradovatelné mikročástice (MČ) na bázi kopolymeru kyseliny mléčné a glykolové (PLGA) metodou odpaření rozpouštědla z jednoduché emulze o/v. Mikročástice obsahovaly nerozpustné antidepresivum mirtazapin. Příprava mikročástic zahrnovala formulační proměnné, a to obsah polymeru (700, 900 nebo 1200 mg), dichlormethanu (5 nebo 10 ml), a/nebo léčiva (200 nebo 400 nebo 600 mg) a objem vodné fáze emulze (400, 600 nebo 800 ml). U sledovaných parametrů byl pozorován vliv na velikost mikročástic a jejich morfologii, enkapsulační účinnost a disoluční chování. Všechny mikročástice byly úspěšně připraveny a jejich velikost se pohybovala v intervalu 165,34 ± 42,88 až 360,17 ± 121,59 μm. Mikročástice vykazovaly prodloužené uvolňování léčiva (v rámci dní), přičemž u některých z nich byl pozorován vícefázový charakter. Bylo zjištěno, že při použití vyššího počátečního množstvím PLGA byly připraveny větší MČ s delším lag time, a to až 34,3 hodin. Na druhé straně vyšší množství použitého léčiva vedlo ke zkrácení lag time. Snížení objemu vnější fáze a násobně vyšší množství dichlormethanu zpomalilo uvolňování mirtazapinu a snížilo enkapsulační účinnost. Výsledky byly dále potvrzeny vícerozměrnou analýzou dat.
In this experimental study, the biodegradable polylactide-co-glycolide (PLGA) microparticles (MP) loaded with the insoluble antidepressant mirtazapine were prepared by the simple o/w solvent evaporation method. The formation involved intrinsic variables, such as the content of polymer (700, 900 or 1200 mg), dichloromethane (5 or 10 ml) and/or drug (200 or 400 or 600 mg), and the volume of the aqueous emulsion phase (400, 600 or 800 ml). The influence of these parameters on the size and morphology of microparticles, encapsulation efficiency, and drug release behavior was observed. All MP were successfully prepared, and their size ranged between 165.34 ± 42.88 and 360.17 ± 121.59 μm. MP exhibited prolonged drug release (days), and some profiles had multiphasic character. It was found that the samples prepared with a higher initial amount of PLGA were bigger with prolonged lag time up to 34.3 hours. On the other hand, higher drug concentrations reduced the lag time. The external phase volume reduction and multiplication of dichloromethane amount prolonged the mirtazapine release and decreased the encapsulation efficiency. These observations were further confirmed by multivariate data analysis.
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Cílem tohoto projektu jsou in vitro a in vivo hodnocení nově připravených a charakterizovaných nanokompozitních nosičů se strukturními a mechanickými vlastnostmi optimálními pro osazování mesenchymálními kmenovými buňkami (MSC). Jejich navrhované složení bude kombinovat výhody biodegradabilních alifatických polyesterů ve formě nanovláken, přírodního kolagenu jako matrice, a přírodního kalcium fosfátu ve formě nanočástic, to vše doplněno hyaluronanem sodným. Proces přípravy bude optimalizován s cílem dosažení homogenně porézní mikrostruktury se vzájemně propojenými póry s nano/mikro strukturovaným povrchem, s vhodnými mechanickými vlastnostmi a řízenou dobou biodegradace a to vše s ohledem na získání optimálního systému pro osazování MSC. Výsledky získané pomocí testů in vitro budou využity v testech in vivo na modelu miniaturních prasat.; Newly prepared and characterized nanocomposite scaffolds with suitable structural and mechanical properties for colonization with mesenchymal stem cells promoting the regeneration of defective bone tissue with the required rate of safe biodegradation will be evaluated on the basis of in vitro and in vivo tests. Their proposed composition will combine the advantages of biodegradable polylactide electrospun nanofibers, natural collagen matrix supplemented with sodium hyaluronate and natural calcium phosphate nanoparticles. The preparation process will be optimized, aiming at an interconnected and homogeneously porous material with a nano/microstructured surface, outstanding mechanical properties and a controlled rate of biodegradation capable of withstanding dynamic culture conditions and encouraging homogeneous mesenchymal stem cell (MSC) colonization. This will be tested in vitro, and the acquired knowledge will be transferred to in vivo experiments with miniature pigs.
- MeSH
- Calcium Phosphates therapeutic use MeSH
- Collagen therapeutic use MeSH
- Mesenchymal Stem Cells MeSH
- Nanocomposites MeSH
- Polyesters therapeutic use MeSH
- Bone Regeneration MeSH
- Materials Testing MeSH
- Absorbable Implants MeSH
- Conspectus
- Ortopedie. Chirurgie. Oftalmologie
- NML Fields
- ortopedie
- technika lékařská, zdravotnický materiál a protetika
- NML Publication type
- závěrečné zprávy o řešení grantu AZV MZ ČR
