RESUMEN
In the present study, chitosan-based wound dressings loaded with the extract of Opuntia ficus-indica (OPU) were prepared. OPU is known for its capability to accelerate skin injury repair. Chitosan (Ch) was crosslinked with a low molecular weight diepoxy-poly(ethylene glycol) (diePEG), and hydrogel films with different Ch/PEG composition and OPU content were prepared by casting. The occurrence of crosslinking reaction was confirmed by FTIR spectroscopy. FTIR and DSC analysis suggested that ionic interactions occur between chitosan and OPU. Tensile tests evidenced that the crosslinking caused a decrease of Young's modulus, which approaches the value of the human skin modulus. Swelling characteristics, water vapor transmission rate, and release kinetics demonstrated that these films are adequate for the proposed application. Finally, a scratch test on a keratinocytes monolayer showed that the rate of cell migration in the presence of OPU-loaded samples is about 3-fold higher compared to unloaded films, confirming the repairing activity of OPU.
Asunto(s)
Quitosano/química , Metilgalactósidos/química , Opuntia/química , Extractos Vegetales/farmacología , Polietilenglicoles/química , Cicatrización de Heridas/efectos de los fármacos , Vendajes , Materiales Biocompatibles/química , Reactivos de Enlaces Cruzados/química , Sistemas de Liberación de Medicamentos/métodos , Módulo de Elasticidad , Células HaCaT , Humanos , Hidrogeles/química , Extractos Vegetales/química , Piel/lesiones , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Resistencia a la TracciónRESUMEN
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.
Asunto(s)
Alginatos/química , Sistemas de Liberación de Medicamentos , Fibroínas/química , Células Madre Mesenquimatosas/efectos de los fármacos , Simvastatina/análogos & derivados , Células Cultivadas , Humanos , Ácido Láctico , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Simvastatina/administración & dosificaciónRESUMEN
In this paper we propose polysaccharide hydrogels combining alginate (ALG) and hyaluronan (HA) as biofunctional platform for dermal wound repair. Hydrogels produced by internal gelation were homogeneous and easy to handle. Rheological evaluation of gelation kinetics of ALG/HA mixtures at different ratios allowed understanding the HA effect on ALG cross-linking process. Disk-shaped hydrogels, at different ALG/HA ratio, were characterized for morphology, homogeneity and mechanical properties. Results suggest that, although the presence of HA does significantly slow down gelation kinetics, the concentration of cross-links reached at the end of gelation is scarcely affected. The in vitro activity of ALG/HA dressings was tested on adipose derived multipotent adult stem cells (Ad-MSC) and an immortalized keratinocyte cell line (HaCaT). Hydrogels did not interfere with cell viability in both cells lines, but significantly promoted gap closure in a scratch assay at early (1 day) and late (5 days) stages as compared to hydrogels made of ALG alone (p<0.01 and 0.001 for Ad-MSC and HaCaT, respectively). In vivo wound healing studies, conducted on a rat model of excised wound indicated that after 5 days ALG/HA hydrogels significantly promoted wound closure as compared to ALG ones (p<0.001). Overall results demonstrate that the integration of HA in a physically cross-linked ALG hydrogel can be a versatile strategy to promote wound healing that can be easily translated in a clinical setting.
Asunto(s)
Alginatos/farmacología , Ácido Hialurónico/farmacología , Hidrogeles/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Línea Celular , Movimiento Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Reactivos de Enlaces Cruzados/farmacología , Modelos Animales de Enfermedad , Ácido Glucurónico/farmacología , Ácidos Hexurónicos/farmacología , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratas Wistar , Reología/efectos de los fármacosRESUMEN
In this paper we propose an in situ forming ionically cross-linked alginate (Alg) hydrogel delivering a Tea Tree Oil microemulsion (MeTTO) and potentially useful as an advanced dressing for infected wounds. Alg hydrogels were prepared by a spray-by-spray deposition method with the aim to minimize the discomforts during application. From pseudoternary phase diagrams, it was found that proper combination of TTO, water, polysorbate 80 and ethanol gave stable spherical MeTTO with good antimicrobial activity. On this basis, MeTTO at 20% TTO was selected for further inclusion in an Alg hydrogel prepared by alternating sprays of Alg/MeTTO and calcium chloride solutions. Homogeneous dispersion of MeTTO inside cross-linked Alg was assessed by different macroscopic and microscopic methods demonstrating the superior propensity of MeTTO to be integrated in the water-based hydrogel as compared to TTO. Antimicrobial effect of Alg/MeTTO hydrogels on Escherichia Coli strains was remarkable, highlighting the potential of the system as bioactive wound dressing.