RESUMEN
Magnetic microspheres have promising application in biomedical field. In this paper, biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCEC) triblock copolymers were synthesized by ring-opening polymerization method. Through adjusting the epsilon-CL/PEG weight ratio in feed, PCEC copolymers with different block ratio were obtained. A novel modified solvent diffusion method was described to prepare magnetic PCEC composite microspheres containing magnetite nanoparticles. The particle size of microsphere decreased with increase in the PEG/PCL block ratio. The obtained microspheres could response to external magnetic field. This study described a novel method to prepare magnetic microspheres. The obtained magnetic polymeric microspheres might have potential application in drug delivery system or disease diagnosis field.
Asunto(s)
Materiales Biocompatibles/química , Glicoles de Etileno/química , Separación Inmunomagnética , Poliésteres/química , Solventes/química , Difusión , Magnetismo , Ensayo de Materiales , Polímeros/químicaRESUMEN
In this work, biodegradable PCL-PEG-PCL (PCEC) triblock copolymers were successfully synthesized at one-step. Aqueous solution of PCEC copolymer displayed thermosensitive sol-gel-sol transition behavior, which is flowing sol at low temperature and turns into non-flowing gel at body temperature. The cytotoxicity of PCEC copolymer was evaluated by cell viability assay using HEK293 and WISH cells. In vivo gel-formation, degradation test, acute toxicity tests, and histopathological study of PCEC hydrogels were performed in BALB/c mice by subcutaneous administration. In acute toxicity test, the mice were observed continuously for 21 days. For histopathologic study, samples including heart, liver, spleen, lung, kidneys, and tissue of injection site were histochemical prepared and stained with hematoxylin-eosin. No mortality or significant signs of acute toxicity was observed during the whole observation period and there is no significant lesion to be shown in histopathologic study of major organs and tissue of injection site. The maximum tolerance dose (MTD) of PCEC hydrogel (20 wt%) by subcutaneous administration was calculated to be higher than 25 g/kg b.w. The results indicated that the obtained PCEC hydrogel was non-toxic after subcutaneous administration, and could be a safe candidate for in situ gel-forming controlled drug delivery system.
Asunto(s)
Hidrogeles/química , Hidrogeles/toxicidad , Poliésteres/química , Poliésteres/toxicidad , Polietilenglicoles/química , Polietilenglicoles/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Cromatografía en Gel , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Femenino , Glucosa/química , Humanos , Inyecciones Intraperitoneales , Espectroscopía de Resonancia Magnética , Masculino , Dosis Máxima Tolerada , Ratones , Ratones Endogámicos BALB C , Soluciones , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
In this paper, biodegradable poly(epsilon-caprolactone)-poly(ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) triblock copolymer was synthesized, and was characterized by FTIR, 1H-NMR and GPC. The PCL-PEG-PCL/dimethyl sulfoxide (DMSO) solution displayed in situ gelling behavior when subcutaneously injected into the body. Toxicity tests and a histopathological study were performed in BALB/c mice. We focused mainly on acute organ toxicity of BALB/c mice by subcutaneous injection. In the acute toxicity test, the dose of subcutaneous injection was 5 g/kg body weight (b.w.), and the mice were observed continuously for 14 days. For the histopathological study, samples including heart, lung, liver, kidneys, spleen, stomach and intestine were histochemically prepared and stained with hematoxylin-eosin for histopathological examination. No mortality or significant signs of toxicity were observed during the whole observation period, and there is no significant lesion to be shown in histopathological study of major organs in the mice. Therefore, the maximal tolerance dose of dimethyl sulfoxide (DMSO) solution of PCL-PEG-PCL copolymer by subcutaneous injection was calculated to be higher than 5 g/kg b.w. Therefore, the PCL-PEG-PCL/DMSO system was thought to be non-toxic after subcutaneous injection, and it might be a candidate for an in situ gelling controlled drug delivery system.
Asunto(s)
Implantes Absorbibles , Materiales Biocompatibles/química , Sistemas de Liberación de Medicamentos , Poliésteres/química , Polietilenglicoles/química , Polímeros/química , Animales , Peso Corporal , Cromatografía de Gases/métodos , Dimetilsulfóxido/química , Espectroscopía de Resonancia Magnética/métodos , Ratones , Ratones Endogámicos BALB C , Poliésteres/toxicidad , Polietilenglicoles/toxicidad , Polímeros/toxicidad , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Distribución TisularRESUMEN
In this work, a new kind of biodegradable pH-sensitive hydrogel was successfully synthesized by UV-initiated free radical polymerization. The obtained hydrogel was characterized by (1)H NMR and FTIR. Swelling behavior in different aqueous media and pH responsivity of the hydrogels were studied in detail as well. With increase in pH from 1.2 to 7.2, swelling ratio of the hydrogel increased. The morphology was observed by scanning electron microscopy, and the hydrolytic degradation behavior was also investigated in this work.