Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 42
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Int J Mol Sci ; 22(13)2021 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-34201769

RESUMO

Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels' mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.


Assuntos
Materiais Biocompatíveis/química , Gelatina/química , Ácido Hialurônico/química , Hidrogéis/química , Metacrilatos/química , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Humanos , Polímeros/química
2.
Carbohydr Polym ; 175: 645-653, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28917913

RESUMO

In the present work, we propose silk fibroin/alginate (SF/Alg) beads embedding simvastatin-loaded biodegradable microparticles as a versatile platform capable of tuning SVA release and in so doing osteogenic effects. In a first part of the study, microparticles of poly(lactic-co-glycolic) acid incorporating simvastatin either as lactone (SVL) or as hydroxyacid form (SVA) were prepared by spray-drying. While SVA-loaded microparticles released the drug in three days, long-term release of SVA could be obtained from SVL-loaded microparticles. In this latter case, SVL was promptly transformed to the osteogenic active SVA during release. When tested on mesenchymal stem cells, a time- and dose-dependent effect of SVL-loaded microparticles on cell proliferation and alkaline phosphatase (ALP) activity was found. Thereafter, SVL-loaded microparticles were embedded in SF/Alg beads to limit the initial simvastatin burst and to achieve easier implantation as well. Microparticle-embedded beads showed no cytotoxicity while ALP activity increased. If correctly exploited, the developed system may be suitable as osteogenic polymer scaffolds releasing correct amount of the drug locally for long time-frames.


Assuntos
Alginatos/química , Sistemas de Liberação de Medicamentos , Fibroínas/química , Células-Tronco Mesenquimais/efeitos dos fármacos , Sinvastatina/análogos & derivados , Células Cultivadas , Humanos , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Sinvastatina/administração & dosagem
3.
J Food Sci Technol ; 53(6): 2817-26, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27478238

RESUMO

New active films based on chitosan and polycaprolactone blends and containing α-tocopherol were designed for food packaging applications. Mechanical properties, stability against temperature and swelling degree in 50 % ethanol (v/v) were evaluated. Migration kinetics of α-tocopherol from the developed films into butter and food simulants [50 % ethanol (v/v), 95 % ethanol (v/v), and isooctane] at different temperatures were studied. α-Tocopherol was quantified in the food simulants by means of high performance liquid chromatography with diode-array detection at 292 nm. The proposed method exhibited a good sensitivity with a limit of detection of 0.1 mg/L. The kinetics release of α-tocopherol was characterized by determining the partition and the diffusion coefficients by using a mathematical modeling based on Fick's Second Law. The diffusion coefficients obtained ranged between 1.03 × 10(-13) and 2.24 × 10(-12) cm(2)/s for 95 % ethanol (v/v) at 4 and 20 °C, respectively. Developed films maintained the antioxidant activity for more than 20 days.

4.
Int J Pharm ; 495(1): 463-473, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26362078

RESUMO

The aim of this study was to evaluate the osteoinductive capacity of a poloxamine (Tetronic(®) 908, T) and α-cyclodextrin (αCD) supramolecular gel (T-CD) as scaffold in a critical size defect in rat calvaria. The T-CD gel was evaluated solely and after being loaded with simvastatin (SV) and bone morphogenetic protein (BMP-2) separately and in combinations in order to reduce the doses of the active substances. Three doses of SV (7.5, 75, 750 µg) and two doses of BMP-2 (3 and 6 µg) were tested. The histology and histomorphometrical analysis showed improved bone repair with T-CD compared to T, probably due to better release control of both SV and BMP-2. In addition, as T-CD eroded more slowly than poloxamine alone, it remained longer in the defect site. Although synergism was not obtained with BMP-2 and SV, according to the observed regeneration of the defect, the dose of BMP-2 and SV can be reduced to 3 µg and 7.5 µg, respectively.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Polietilenoglicóis/administração & dosagem , Propilenoglicóis/administração & dosagem , Sinvastatina/administração & dosagem , Crânio/cirurgia , alfa-Ciclodextrinas/química , Animais , Proteína Morfogenética Óssea 2/farmacologia , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Liberação Controlada de Fármacos , Géis/química , Masculino , Polietilenoglicóis/química , Polietilenoglicóis/farmacologia , Propilenoglicóis/química , Propilenoglicóis/farmacologia , Ratos , Ratos Sprague-Dawley , Sinvastatina/farmacologia , Alicerces Teciduais , Viscosidade
5.
Biomater Sci ; 3(4): 581-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26222417

RESUMO

We propose a novel hanging spherical drop system for anchoring arrays of droplets of cell suspension based on the use of biomimetic superhydrophobic flat substrates, with controlled positional adhesion and minimum contact with a solid substrate. By facing down the platform, it was possible to generate independent spheroid bodies in a high throughput manner, in order to mimic in vivo tumour models on the lab-on-chip scale. To validate this system for drug screening purposes, the toxicity of the anti-cancer drug doxorubicin in cell spheroids was tested and compared to cells in 2D culture. The advantages presented by this platform, such as feasibility of the system and the ability to control the size uniformity of the spheroid, emphasize its potential to be used as a new low cost toolbox for high-throughput drug screening and in cell or tissue engineering.


Assuntos
Materiais Biocompatíveis/química , Avaliação Pré-Clínica de Medicamentos/instrumentação , Ensaios de Triagem em Larga Escala/métodos , Esferoides Celulares/citologia , Engenharia Tecidual/métodos , Antineoplásicos/química , Antineoplásicos/farmacologia , Biomimética , Biotecnologia , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Humanos
6.
Carbohydr Polym ; 117: 797-806, 2015 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-25498702

RESUMO

Polysaccharide-based aerogels in the form of microspheres were investigated as carriers of poorly water soluble drugs for oral administration. These bio-based carriers may combine the biocompatibility of polysaccharides and the enhanced drug loading capacity of dry aerogels. Aerogel microspheres from starch, pectin and alginate were loaded with ketoprofen (anti-inflammatory drug) and benzoic acid (used in the management of urea cycle disorders) via supercritical CO2-assisted adsorption. Amount of drug loaded depended on the aerogel matrix structure and composition and reached values up to 1.0×10(-3) and 1.7×10(-3) g/m(2) for ketoprofen and benzoic acid in starch microspheres. After impregnation, drugs were in the amorphous state in the aerogel microspheres. Release behavior was evaluated in different pH media (pH 1.2 and 6.8). Controlled drug release from pectin and alginate aerogel microspheres fitted Gallagher-Corrigan release model (R(2)>0.99 in both cases), with different relative contribution of erosion and diffusion mechanisms depending on the matrix composition. Release from starch aerogel microspheres was driven by dissolution, fitting the first-order kinetics due to the rigid starch aerogel structure, and showed different release rate constant (k1) depending on the drug (0.075 and 0.160 min(-1) for ketoprofen and benzoic acid, respectively). Overall, the results point out the possibilities of tuning drug loading and release by carefully choosing the polysaccharide used to prepare the aerogels.


Assuntos
Portadores de Fármacos/química , Microesferas , Polissacarídeos/química , Administração Oral , Ácido Benzoico/administração & dosagem , Ácido Benzoico/química , Liberação Controlada de Fármacos , Géis , Concentração de Íons de Hidrogênio , Cetoprofeno/administração & dosagem , Cetoprofeno/química , Cinética , Solubilidade , Água/química
7.
Acta Biomater ; 10(10): 4314-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24937139

RESUMO

Superamphiphobic surfaces were evaluated as a tool to prepare spherical particles from polymers and solvents of very diverse nature, under mild conditions and with 100% drug encapsulation yield. Different from bioinspired superhydrophobic surfaces suitable only for aqueous dispersions, the superamphiphobic platforms allowed the formation of spherical droplets when solvents of any polarity were deposited onto them. Spherical poly(d,l-lactide-co-glycolide) (PLGA) particles were synthesized by placing drops of PLGA/ciprofloxacin suspensions in dioxane on a superamphiphobic surface followed by solvent evaporation. The particles prepared covering a wide range of PLGA/ciprofloxacin weight ratios delivered a 20% dose in the first 24h and then sustained the release of the remaining drug for more than 1month. The particles, both freshly prepared and after being 26days in the release medium, showed efficiency against different types of microorganisms. The developed polymer- and solvent-independent approach could be useful for microencapsulation with very high efficiency of active substances of varied nature into size-tunable particles for a wide range of applications in an affordable and cost-effective manner.


Assuntos
Antibacterianos , Bactérias/crescimento & desenvolvimento , Ciprofloxacina , Portadores de Fármacos , Ácido Láctico , Microesferas , Ácido Poliglicólico , Antibacterianos/química , Antibacterianos/farmacologia , Ciprofloxacina/química , Ciprofloxacina/farmacologia , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacologia , Dioxanos/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacologia , Ácido Láctico/química , Ácido Láctico/farmacologia , Tamanho da Partícula , Ácido Poliglicólico/química , Ácido Poliglicólico/farmacologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico
8.
J Biomed Nanotechnol ; 10(6): 959-69, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24749391

RESUMO

The aim of this study was to confirm previously shown, in vitro osteogenic induction by the Tetronics T908 and T1307 in a critical-size, rat calvaria defect. In vivo, the osteogenic activity of the hydrogels was comparable to in vitro, but less pronounced. However, similar to in vitro, the system was strongly potentiated by incorporating 6.5 microg of bone morphogenetic protein-2 in solution or pre-encapsulated in poly(lactic-co-glycolic) acid microspheres. These two systems extended the in vivo release of bone morphogenetic protein-2, determined with 125I- bone morphogenetic protein-2, for one and two additional weeks, respectively, time enough to fill approximately 40% and 90% of the defect with well-organized bone. Furthermore, the structural characteristics of Tetronic hydrogels together with their biocompatibility, injectability, and adaptability to multiple defect sizes and shapes suggest their role as new, potential bone morphogenetic protein-2 delivery, low-cost scaffolds for minor as well as critical bone defects.


Assuntos
Proteína Morfogenética Óssea 2/administração & dosagem , Regeneração Óssea/efeitos dos fármacos , Implantes de Medicamento/administração & dosagem , Etilenodiaminas/administração & dosagem , Etilenodiaminas/química , Nanocápsulas/administração & dosagem , Fraturas Cranianas/tratamento farmacológico , Animais , Proteína Morfogenética Óssea 2/química , Difusão , Implantes de Medicamento/química , Géis/química , Masculino , Nanocápsulas/química , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Fraturas Cranianas/patologia , Resultado do Tratamento
9.
Int J Pharm ; 461(1-2): 286-95, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24333904

RESUMO

Glycidyl methacrylate (GMA) and acrylic acid (AAc) were separately grafted onto polypropylene (PP) monofilament sutures by means of pre-irradiation using a (60)Co γ-source, with the purpose of loading vancomycin via (i) covalent immobilization through the glycidyl groups of GMA and (ii) ionic interaction with AAc moieties. The effect of absorbed radiation dose, monomer concentration, temperature and reaction time on the grafting degree was evaluated in detail. GMA grafting ranged from 25% to 800% while the grafting yield of AAc onto PP could be tuned between 9% and 454%, at doses from 5 to 50 kGy and a dose rate 13.7 kGy/h. Grafting of GMA or AAc decreased the decomposition temperature and made the sutures swellable to a certain extent. GMA grafting led to a continuous, smooth and thick coating, which was suitable for immobilization of up to 1.9 µg vancomycin per gram. The immobilized vancomycin enabled a reduction in the Staphylococcus aureus CFU adhered to the suture surface. On the other hand, dried AAc-functionalized sutures exhibited a rough and cracked surface which was responsible for a minor increase in the coefficient of friction. PP-g-AAc sutures exhibited pH-dependent swelling and remarkably high capability to host vancomycin (up to 109.9 mg/g), particularly those with an intermediate degree of grafting. Some AAc-functionalized sutures were shown able to inhibit bacterial growth after successive challenges with fresh lawns. Therefore, tuning the yield of grafting of GMA or AAc may enable the preparation of drug-suture combination products that retain or release, respectively, antimicrobial agents.


Assuntos
Polímeros/química , Polipropilenos/química , Suturas , Vancomicina/administração & dosagem , Acrilatos/química , Adsorção , Antibacterianos/administração & dosagem , Antibacterianos/química , Antibacterianos/farmacologia , Compostos de Epóxi/química , Fricção , Concentração de Íons de Hidrogênio , Metacrilatos/química , Staphylococcus aureus/efeitos dos fármacos , Temperatura , Vancomicina/química , Vancomicina/farmacologia
10.
J Mater Chem B ; 2(30): 4943-4956, 2014 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32261787

RESUMO

Polymeric particles acting as sources of biological cues to promote tissue regeneration are currently an interesting topic in bone tissue engineering research. In this study, microspheres of dextran-methacrylate (dextran-MA) and γ-cyclodextrins (γ-CD) for the delivery of osteogenic agents were prepared by means of photopolymerization on biomimetic superhydrophobic surfaces. The effects of the incorporation of the γ-CD units as free entities or as structural monomers (acrylamidomethyl-γ-cyclodextrin, γ-CD-NMA) on dexamethasone loading and release performance were evaluated in detail in order to achieve osteogenic differentiation of human stem cells. The copolymerization of dextran-MA with γ-CD-NMA improved the loading capacity of the particles and also provided a sustained release of dexamethasone for several days. The biological studies revealed that such microspheres were cytocompatible and capable of inducing the differentiation of human adipose-derived stem cells (hASCs) to osteoblasts, as determined from an increase of alkaline phosphatase (ALP) activity between days 3 and 7. Such results were also confirmed using ALP staining. Therefore, immobilization of γ-CDs onto the dextran-MA network may be particularly useful for the development of cytocompatible implantable spherical biomaterials for bone tissue engineering purposes.

11.
Carbohydr Polym ; 98(2): 1343-52, 2013 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-24053812

RESUMO

Efficient ophthalmic therapy requires the development of strategies that can provide sufficiently high drug levels in the ocular structures for a prolonged time. This work focuses on the suitability of poly-(cyclo)dextrins as carriers able to solubilize the carbonic anhydrase inhibitor (CAI) ethoxzolamide (ETOX), which is so far used for oral treatment of glaucoma. Topical ocular treatment should notably enhance the efficiency/safety profile of the drug. Natural α-, ß- and γ-cyclodextrins and a maltodextrin were separately polymerized using citric acid as cross-linker agent under mild conditions. The resultant hydrophilic polymers exhibited larger capability to solubilize ETOX than the pristine (cyclo)dextrins. Moreover, they provided sustained drug diffusion in artificial lachrymal fluid. Interestingly the poly-(cyclo)dextrins solutions facilitate the loading of remarkably high doses of ETOX in poly(2-hydroxyethyl methacrylate)-based contact lenses. Exploiting ionic interactions between functional groups in the contact lenses and remnant free carboxylic acids in the citric acid linkers of poly-(cyclo)dextrins led to the retention of the drug-loaded poly-(cyclo)dextrins and, in turn, to sustained release for several weeks.


Assuntos
Inibidores da Anidrase Carbônica/química , Ciclodextrinas/química , Preparações de Ação Retardada/síntese química , Portadores de Fármacos/síntese química , Etoxzolamida/química , Soluções Oftálmicas/química , Inibidores da Anidrase Carbônica/farmacologia , Ácido Cítrico/química , Lentes de Contato , Reagentes de Ligações Cruzadas/química , Etoxzolamida/farmacologia , Interações Hidrofóbicas e Hidrofílicas , Metacrilatos/química , Soluções Oftálmicas/farmacologia , Polimerização , Solubilidade
12.
Int J Pharm ; 456(2): 269-81, 2013 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-24008084

RESUMO

A supercritical carbon dioxide (scCO2)-assisted foaming/mixing method (SFM) was implemented for preparing dexamethasone (DXMT)-loaded poly(ε-caprolactone)/silica nanoparticles (PCL/SNPs) composite materials suitable for bone regeneration. The composites were prepared from PCL and mesoporous SNPs (MCM-41/SBA-15) by means of scCO2-assisted SFM at several operational pressures, processing times and depressurization conditions. DXMT was loaded into SNPs (applying a scCO2 solvent impregnation/deposition method - SSID) and into PCL/SNPs composites (using the SFM method). The effects of the employed operational and compositional variables on the physicochemical and morphological features as well as in the in vitro release profiles of DXMT were analyzed in detail. This work demonstrates that the above-referred scCO2-based methods can be very useful for the preparation of DXMT-loaded PCL/SNPs composites with tunable physicochemical, thermomechanical, morphological and drug release properties and suitable for hard-tissue regeneration applications.


Assuntos
Dióxido de Carbono/química , Cromatografia com Fluido Supercrítico/métodos , Dexametasona/síntese química , Nanopartículas/química , Poliésteres/síntese química , Dióxido de Silício/síntese química , Difração de Raios X
13.
Mol Pharm ; 10(8): 3232-41, 2013 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-23763603

RESUMO

Amphiphilic polymeric micelles greatly improve the solubilization and sustained release of hydrophobic drugs and provide a protective environment for the cargo molecules in aqueous media, which favors lower drug administration doses, reduces adverse side effects, and increases blood circulation times and passive targeting to specific cells. These capabilities depend, among other variables, on the structure and composition of the polymer chains. Composition and, in particular, block length have been shown to play an important role in the modification of cellular responses such as drug internalization processes or transduction pathways when polymeric unimer/micelles are in close contact with cells. Here we present a detailed study about the role copolymer structure and composition play on cell viability and cellular response of several cell lines. To do that, more than 30 structurally related copolymers with diblock and triblock architectures containing different hydrophobic blocks and poly(ethylene oxide) as the common hydrophilic unit have been analyzed regarding cytocompatibility and potential as "active" cell response modifiers by testing their influence on the P-gp pump efflux mechanism responsible of multidrug resistance in cancerous cells. An empirical threshold for cell viability could be established at a copolymer EO/POeffective value above ca. 1.5 for copolymers with triblock structure, whereas no empirical rule could be observed for diblocks. Moreover, some of the tested copolymers (e.g., BO12EO227BO12 and EO57PO46EO57 that notably increased and C16EO455C16 that decreased the P-gp ATPase activity) were observed to act as efficient inhibitors of the P-gp efflux pump promoting an enhanced doxorubicin (DOXO) accumulation inside multidrug resistant (MDR) NCI-ADR-RES cells.


Assuntos
Polímeros/química , Subfamília B de Transportador de Cassetes de Ligação de ATP/química , Animais , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos , Camundongos , Microscopia Confocal , Polímeros/efeitos adversos , Relação Estrutura-Atividade , Verapamil/química
14.
Int J Pharm ; 445(1-2): 47-57, 2013 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-23380628

RESUMO

Five reverse poly(butylene oxide)-poly(ethylene oxide)-poly(butylene oxide) block copolymers, BOnEOmBOn, with BO ranging from 8 to 21 units and EO from 90 to 411 were synthesized and evaluated as efficient chemotherapeutic drug delivery nanocarriers and inhibitors of the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line. The copolymers were obtained by reverse polymerization of poly(butylene oxide), which avoids transfer reaction and widening of the EO block distribution, commonly found in commercial poly(ethylene oxide)-poly(propylene oxide) block copolymers (poloxamers). BOnEOmBOn copolymers formed spherical micelles of 10-40 nm diameter at lower concentrations (one order of magnitude) than those of equivalent poloxamers. The influence of copolymer block lengths and BO/EO ratios on the solubilization capacity and protective environment for doxorubicin (DOXO) was investigated. Micelles showed drug loading capacity ranging from ca. 0.04% to 1.5%, more than 150 times the aqueous solubility of DOXO, and protected the cargo from hydrolysis for more than a month due to their greater colloidal stability in solution. Drug release profiles at various pHs, and the cytocompatibility and cytotoxicity of the DOXO-loaded micelles were assessed in vitro. DOXO loaded in the polymeric micelles accumulated more slowly inside the cells than free DOXO due to its sustained release. All copolymers were found to be cytocompatible, with viability extents larger than 95%. In addition, the cytotoxicity of DOXO-loaded micelles was higher than that observed for free drug solutions in a MDR ovarian NCI-ADR-RES cell line which overexpressed P-gp. The inhibition of the P-gp efflux pump by some BOnEOmBOn copolymers, similar to that measured for the common P-gp inhibitor verapamil, favored the retention of DOXO inside the cell increasing its cytotoxic activity. Therefore, poly(butylene oxide)-poly(ethylene oxide) block copolymers offer interesting features as cell response modifiers to complement their role as efficient nanocarriers for cancer chemotherapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Polietilenoglicóis/administração & dosagem , Células 3T3 , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Camundongos , Micelas
15.
J Control Release ; 167(1): 68-75, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23352909

RESUMO

Two poly(styrene oxide)-poly(ethylene oxide) (PSO-PEO) triblock copolymers with different chain lengths were analyzed as potential chemotherapeutic nanocarriers, and their ability to inhibit the P-glycoprotein (P-gp) efflux pump in a multidrug resistant (MDR) cell line were measured in order to establish possible cell-responses induced by the presence of the copolymer molecules. Thus, EO33SO14EO33 and EO38SO10EO38 polymeric micelles were tested regarding doxorubicin (DOXO) entrapment efficiency (solubilization test), physical stability (DLS), cytocompatibility (fibroblasts), release profiles at various pHs (in vitro tests), as well as P-gp inhibition and evasion and cytotoxicity of the DOXO-loaded micelles in an ovarian MDR NCI-ADR/RES cell line and in DOXO-sensitive MCF-7 cells. EO33SO14EO33 and EO38SO10EO38 formed spherical micelles (~13nm) at lower concentration than other copolymers under clinical evaluation (e.g. Pluronic®), exhibited 0.2% to 1.8% loading capacity, enhancing more than 60 times drug apparent solubility, and retained the cargo for long time. The copolymer unimers inhibited P-gp ATPase activity in a similar way as Pluronic P85, favoring DOXO accumulation in the resistant cell line, but not in the sensitive cell line. DOXO loaded in the micelles accumulated more slowly inside the cells, but caused greater cytotoxicity than free drug solutions in the NCI-ADR-RES cell line, which overexpressed P-gp. Hence, PSO-PEO block copolymers offer interesting features as new biological response modifiers to be used in the design of efficient nanocarriers for cancer chemotherapy.


Assuntos
Antibióticos Antineoplásicos/administração & dosagem , Doxorrubicina/administração & dosagem , Portadores de Fármacos/administração & dosagem , Nanopartículas/administração & dosagem , Polietilenoglicóis/administração & dosagem , Poliestirenos/administração & dosagem , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adenosina Trifosfatases/metabolismo , Antibióticos Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/química , Portadores de Fármacos/química , Resistencia a Medicamentos Antineoplásicos , Estabilidade de Medicamentos , Humanos , Micelas , Nanopartículas/química , Polietilenoglicóis/química , Poliestirenos/química
16.
Eur J Pharm Biopharm ; 80(1): 103-12, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22005155

RESUMO

The ability of Pluronic® F127 to form supramolecular gels in the presence of αCD has been explored as a way to design syringeable gel formulations able to sustain drug release while using the lowest proportion of both components. The effects of αCD concentration range (0-9.7% w/v) in copolymer (6.5%, 13% and 20%) gel features were evaluated at 4, 20 and 37°C. An effective complexation of Pluronic and αCD was evidenced as a change in the surface pressure of the π-A isotherm of Pluronic on a subphase of CD solution and the apparition of new peaks in the X-ray spectra. Once the Pluronic and αCD solutions were mixed, the systems became progressively turbid solutions or white gels. The greater the αCD concentration was, the faster the gel formation. The supramolecular hydrogels were thixotropic and those containing 5% or more αCD had G' values above G″ at room temperature, but they were still easily syringeable. The values of both moduli increased as temperature raised; the effect being more evident for 13% and 20% w/v copolymer. The gels prepared with low proportions of αCD exhibited phase separation in few days, particularly when stored at 4 or 37 °C. By contrast, those prepared with 6.5% copolymer were stable for at least two months when stored at 20 °C. The gels were able to sustain vancomycin release for several days; the higher the αCD proportion, the slower the release was. Furthermore, the drug-loaded gels showed activity against Staphylococcus aureus. The results obtained highlight the role of the αCD concentration on the tuning of the rheological features and drug release profiles from Pluronic gels.


Assuntos
Hidrogéis/química , Poloxâmero/química , Seringas , Vancomicina/química , alfa-Ciclodextrinas/química , Química Farmacêutica/métodos , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Estabilidade de Medicamentos , Hidrogéis/administração & dosagem , Poloxâmero/administração & dosagem , Polímeros/administração & dosagem , Polímeros/química , Reologia/métodos , Soluções/química , Staphylococcus aureus/efeitos dos fármacos , Temperatura , Vancomicina/administração & dosagem , Viscosidade , alfa-Ciclodextrinas/administração & dosagem
17.
Curr Drug Targets ; 12(8): 1112-30, 2011 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-21443477

RESUMO

Drug carriers tailored to fit the physicochemical properties of anticancer agents and the therapeutic peculiarities of tumor management are envisioned for improving the effectiveness/toxicity ratio of the current treatments. Polymeric micelles are attracting much attention owing to their unique beneficial features: i) core-shell structure capable to host hydrophobic drugs, raising the apparent solubility in aqueous medium; ii) size adequate for a preferential accumulation (passive targeting) within the tumor, exhibiting enhanced permeability and retention (EPR effect), and iii) unimers that modulate the activity of efflux pumps involved in multidrug resistance (MDR). This review focuses on amphiphilic poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) block copolymers, namely the linear poloxamers (Pluronic® or Lutrol®) and the X-shaped poloxamines (Tetronic®), as components of polymeric micelles able to play these three roles. Specific facets of poloxamers have been highlighted some years ago, but recently their wide range of possibilities is beginning to be fully elucidated and understood. Poloxamines are new excipients in the cancer arena and the comparison of their performance with that of poloxamers may enable to identify aspects of their architecture relevant for the optimization of micellar carriers. Clinical trials in progress indicate that drug-loaded polymeric micelles are beneficial regarding efficiency, safety, and compliance of the treatment and quality of life of the patients. The fact that some copolymers are already approved for internal use and several chemotherapy agents will be off patent soon may help to bring the clinical use of poloxamer- or poloxamine-based micelles into a reality in the coming years.


Assuntos
Sistemas de Liberação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Micelas , Polietilenoglicóis/química , Polímeros/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/uso terapêutico , Química Farmacêutica , Portadores de Fármacos/química , Composição de Medicamentos , Excipientes/administração & dosagem , Excipientes/química , Humanos , Neoplasias/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Polímeros/administração & dosagem
18.
Ars pharm ; 51(supl.2): 494-497, mayo 2010. graf
Artigo em Espanhol | IBECS | ID: ibc-88673

RESUMO

Introducción: La evaluación de los alumnos universitarios constituye un ámbito de debate muy activo. Elobjetivo de nuestro trabajo fue dilucidar en qué medida la implicación del alumno en la evaluación puedeincrementar su motivación y su rendimiento.Materiales y métodos: Desde el curso 2007-08 propusimos a los alumnos de un grupo de Biofarmacia yFarmacocinética de la licenciatura en Farmacia de la Universidad de Santiago de Compostela, queprepararan, de forma individual o en grupos de dos, preguntas para el examen sobre los contenidos deBiofarmacia. Del total de las preguntas propuestas, los alumnos eligen 10 por votación y el profesor secompromete a poner 2 de ellas en el examen, que consta de un total de 5 preguntas.Resultados y discusión: En los cursos 2007-08 y 2008-09 la participación en la redacción de preguntassuperó el 75%. De las 40 preguntas recibidas, se solaparon aproximadamente el 25%, por lo que a lavotación final llegaron más de 20. La búsqueda de una pregunta que al alumno le pareciese adecuada,sirvió de estímulo para una asimilación progresiva de los conocimientos, constatándose una actitud másactiva en las clases. En el curso 2007-08, el 100% de los alumnos de nuestro grupo presentados al examenaprobaron entre junio y septiembre. Ello se reflejó en un cambio de tendencia en los resultados obtenidospor todos los alumnos de Biofarmacia (140 superaron la materia y 19 no la superaron). En 2008-09,aunque los aprobados descendieron (111 vs. 36 suspensos), se mantuvo el incremento de notables,sobresalientes y matrículas de honor(AU)


Introduction: The evaluation of Universitary students is a very active field of controversy. The aim of ourwork was to elucidate to what extent the students can be involved in their own evaluation in order toimprove their motivation and performance.Materials and methods: Since the 2007-08 academic years we invited the students of our group ofBiopharmaceutics and Pharmacokinetics of the Pharmacy degree at the University of Santiago deCompostela, to prepare questions for the Biopharmaceutics exam. Each student was encouraged toelaborate one question by her/himself or with the help of other student. The students voted 10 questionsamong the total ones proposed and the professor guaranteed that 2 out of those 10 questions would beincluded in the exam, which had 5 questions in total.Results and discussion: During 2007-08 and 2008-09 more than 75% students collaborate in thepreparation of the questions. We received around 40 questions, which were coincident in nearly 25%.Thus, once the repeated questions and those badly formulated were removed, the students could vote 10out of more than 20. The search for an appealing question made the students to be more motivated andhelped them to progressively learn the contents of the subject; the students having a more active behaviorat the lessons. In 2007-08, 100% students of our group pass the exams in June or September. This caused ashift in the qualifications of all students of the Biopharmaceutics and Pharmacokinetics subject (140students pass the exam and 19 failed). In 2008-09 the number of students that pass the subject wassomehow lower (111 vs. 36 who failed), but the increase in the “notable”, “sobresaliente” and “matriculade honor” scores (the highest qualifications) was kept(AU)


Assuntos
Humanos , Masculino , Feminino , Aprendizagem Baseada em Problemas/métodos , Aprendizagem Baseada em Problemas/normas , Aprendizagem , Estudantes de Farmácia/classificação , Estudantes de Farmácia/estatística & dados numéricos , Educação em Farmácia/organização & administração , Educação em Farmácia/normas , Farmacocinética , Educação em Farmácia/tendências , Ensino/organização & administração , Ensino/normas , Ensino/tendências , 50069
19.
Ars pharm ; 51(supl.2): 498-504, mayo 2010. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-88674

RESUMO

Introducción: La puesta en marcha del grado de Farmacia de la Universidad de Santiago de Compostela adaptado al EEES ha supuesto, respecto a la Licenciatura, un cambio importante en la organización de las materias correspondientes al bloque de Farmacia y Tecnología Farmacéutica. En este trabajo se realiza un análisis de las modificaciones relacionadas con la materia Biofarmacia y Farmacocinética.Materiales y métodos: Se ha realizado un análisis comparativo del plan vigente de la Licenciatura de Farmacia (BOE 21 de agosto de 1999) y la propuesta de Grado que entrará en vigor el próximo curso 2010-2011.Resultados y discusión: Esta materia se viene impartiendo en el segundo cuatrimestre del cuarto curso de la licenciatura, con una carga docente de 10 créditos (8 teóricos +2 prácticos). La implantación del grado supone su desdoblamiento en dos asignaturas cuatrimestrales con 4,5 y 6 créditos respectivamente a impartir en el segundo cuatrimestre de cuarto y en el primero de quinto curso. A diferencia de lo que ocurre con la licenciatura, para coordinar la presentación de contenidos sobre formas de dosificación (incluidos en Tecnología Farmacéutica III) y vías de administración, los contenidos de Farmacocinética se impartirán en cuarto curso, reservando la materia de quinto para la Biofarmacia. La modificación de la secuencia de presentación de los contenidos, habrá de combinarse con la intensificación del uso de nuevas metodologías como el uso del aula virtual, la enseñanza basada en la resolución de problemas y el empleo de nuevas aproximaciones para la evaluación de los estudiantes(AU)


Introduction: The implementation of the Degree in Pharmacy adapted to the EHEA in the University of Santiago de Compostela requires important changes in the block of Pharmacy and Pharmaceutical Technology. In this paper the changes related to the subject Biopharmaceutics and Pharmacokinetics are analyzed.Materials and methods: We have carried out a comparative analysis of the current curriculum of Pharmacy (BOE August 21, 1999) and the proposed new Grade that will be launched next academic year (2010-2011).Results and discussion: Until now the subject “Biopharmaceutics and Pharmacokinetics” has been taught during the second semester of the fourth year with 10 credits in total (8 theoretical plus 2 practical). In the new EHEA-adapted Degree, this subject is split into two four-month courses with 4.5 and 6 credits, respectively, to be taught in the second semester of the fourth year and in the first of the fifth one. Differently to the current degree, the contents of Pharmacokinetics will be given before those of Biopharmaceutics. The reasons behind these changes are mainly due to the need of coordination of the biopharmaceutic contents on routes of administration with the Pharmaceutical Technology III (first semester of fifth ) contents on drug dosage forms. To make these changes possible, the use of new methodologies, including the promotion of e-learning and the problem-based learning as well as the implementation of novel approaches for the evaluation of the students, is demanded(AU)


Assuntos
Humanos , Masculino , Feminino , Tecnologia Farmacêutica/métodos , Educação em Farmácia/métodos , Acreditação/legislação & jurisprudência , Acreditação/normas , Acreditação de Instituições de Saúde , Planos e Programas de Saúde/legislação & jurisprudência , Planos e Programas de Saúde/normas , Tecnologia Farmacêutica/normas , Tecnologia Farmacêutica/tendências , Educação em Farmácia/organização & administração , Educação em Farmácia/tendências , Inquéritos e Questionários
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...