RESUMEN
OBJECTIVE: To prove the PLLA-PTX' efficacy on growth, apoptosis of ovarian cancer cell line SKOV3, and to study the controlled release roles of PLLA for PTX. METHODS: Cultured cells of human ovarian Carcinoma cell Line SKOV3 were treated with PLLA-PTX microparticles and PTX only separately, untreated cells as the control. The proliferation of SKOV3 cells were determined by MTT assay with the morphologic change observed under inverted phase contrast microscope, the apoptosis of cell were demonstrated by FCM and in situ TUNEL technique. RESULTS: The anti-tumor activity of PLLA-PTX microparticles was stronger than PTX alone. A time-dependent and dose-dependent growth inhibition was abserved. At 0.05 micromol/L drug concentration, SKOV3 cell viability experiment demonstrated that the drug formulated in the microparticles was more effective than that formulated in PTX. PLLA-PTX microparticles can increase G2/M period percentage, interrupt the cell cycle proceeding, and inhibit the tumor cells'growth through cell apoptosis. Positive staining for the presence of apoptosis were obtained in SKOV3 cells with PLLA-PTX microparticles. CONCLUSIONS: PLLA-PTX microparticles have strong anti-tumor activity and obviously controlled released effectiveness. It shows longer and stronger controlled anti-tumor activity than paclitaxel alone.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Ácido Láctico/farmacología , Neoplasias Ováricas/patología , Paclitaxel/farmacología , Polímeros/farmacología , Línea Celular Tumoral , Proliferación Celular , Preparaciones de Acción Retardada , Femenino , Humanos , Tamaño de la Partícula , PoliésteresRESUMEN
A porous poly(L-lactic acid)/ß-tricalcium phosphate (PLLA/ß-TCP) composite scaffold was fabricated using a novel technique comprising powder mixing, compression molding, low-temperature treatment, and particulate leaching without any organic solvent. The effect of this scaffold on osteoblast proliferation and differentiation was evaluated in vitro. The fabricated scaffold had a homogeneously interconnected porous structure with a porosity of 70% and compressive strength of 1.35 MPa. The methylthiazol tetrazolium values and alkaline phosphatase (ALP) activity of osteoblasts seeded on the solvent-free scaffold were significant higher than those of the control. Using real-time PCR, gene expressions of ALP, osteocalcin, and type 1 collagen were shown to be upregulated. As the method does not use any organic solvent, it eliminates problems associated with organic solvent residue and therefore improves the cell compatibility. It has a promising potential for the preparation of porous scaffold for bone tissue engineering.
Asunto(s)
Fosfatos de Calcio/química , Ácido Láctico/química , Ensayo de Materiales/métodos , Polímeros/química , Andamios del Tejido/química , Animales , Sustitutos de Huesos , Procesos de Crecimiento Celular/fisiología , Fuerza Compresiva , Microscopía Electrónica de Rastreo , Osteoblastos/citología , Poliésteres , Porosidad , Ratas , Ratas Sprague-Dawley , Ingeniería de TejidosRESUMEN
The Fe(3)O(4)-poly(L-lactide) (Fe(3)O(4)-PLLA) magnetic microparticles were successfully prepared in a process of solution-enhanced dispersion by supercritical CO(2) (SEDS), and their morphology, particle size, magnetic mass content, surface atom distribution and magnetic properties were characterized. Indomethacin (Indo) was used as a drug model to produce drug-polymer magnetic composite microparticles. The resulting Fe(3)O(4)-PLLA microparticles with mean size of 803 nm had good magnetic property and a saturation magnetization of 24.99 emu/g. The X-ray photoelectron spectroscopy (XPS) test indicated that most of the Fe(3)O(4) were encapsulated by PLLA, which indicated that the Fe(3)O(4)-PLLA magnetic microparticles had a core-shell structure. After further loading with drug, the Indo-Fe(3)O(4)-PLLA microparticles had a bigger mean size of 901 nm, and the Fourier transform infrared spectrometer (FTIR) analysis demonstrated that the SEDS process was a typical physical coating process to produce drug-polymer magnetic composite microparticles, which is favorable for drugs since there is no change in chemistry. The in vitro cytotoxicity test showed that the Fe(3)O(4)-PLLA magnetic microparticles had no cytotoxicity and were biocompatible, which means there is potential for biomedical application.
Asunto(s)
Sistemas de Liberación de Medicamentos/métodos , Compuestos Férricos/química , Magnetismo , Poliésteres/química , Animales , Materiales Biocompatibles , Dióxido de Carbono , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Composición de Medicamentos , Humanos , Indometacina/administración & dosificación , Tamaño de la PartículaRESUMEN
Poly(L-lactide) (PLLA) microparticles were prepared in supercritical anti-solvent process. The effects of several key factors on surface morphology, and particle size and particle size distribution were investigated. These factors included initial drops size, saturation ratio of PLLA solution, pressure, temperature, concentration of the organic solution, the flow rate of the solution and molecular weight of PLLA. The results indicated that the saturation ratio of PLLA solution, concentration of the organic solution and flow rate of the solution played important roles on the properties of products. Various microparticles with the mean particle size ranging from 0.64 to 6.64 microm, could be prepared by adjusting the operational parameters. Fine microparticles were obtained in a process namely solution-enhanced dispersion by supercritical fluids (SEDS) process with dichloromethane/acetone mixture as solution.