RESUMEN
Supramolecular polymer micelles composed of seven-armed poly(2-methy-2-oxazoline) as the coating and linear poly(dl-lactide) as the core were prepared through synthesizing ß-cyclodextrin-terminated poly(2-methy-2-oxazoline) and adamantine-terminated linear poly(dl-lactide), followed by host-guest interaction between ß-cyclodextrin and adamantine groups in two polymers and self-assembly in aqueous solution. Dynamic light-scattering measurement showed that the micelles based on supramolecular amphiphilic polymers have the size of 119 nm and were highly stable in salt solution. When the micelles were used as the carrier of cabazitaxel, an antitumor agent for drug-resistant cancers, satisfactory drug loading content and encapsulation efficacy were obtained. In vitro cellular cytotoxicity assays found that cabazitaxel-loaded micelles presented obvious cytotoxicity against taxane-sensitive and -resistant cancer cells. Further in vivo antitumor activity evaluation showed that cabazitaxel-loaded micelles have significantly superior efficacy in inhibiting tumor growth and prolonging survival in tumor-bearing mice compared to that of free paclitaxel and free cabazitaxel.
Asunto(s)
Polímeros/química , Animales , Antineoplásicos , Línea Celular Tumoral , Portadores de Fármacos , Sistemas de Liberación de Medicamentos , Ratones , Micelas , PaclitaxelRESUMEN
Lipophilic 6-O-poly (ϵ-caprolactone)-L-ascorbic acid (AA-6-PCL) is synthesized through ROP of ϵ-caprolactone (CL). The number of repeating CL units in the polymer chain varies from 6 to 19. AA-6-PCL loaded supramolecular polymer micelles (SMPMs) are constructed with ß-cyclodextrin (ß-CD) and PCL as blocks. Transmission electron microscopy images show a nanospheric morphology of the micelles with a size range of 43.3 ± 5.0 nm. The drug loading contents are 22.53-39.23% for AA-6-PCL. AA-6-PCL exhibits high radical scavenging capacity (93.96-96.73%) and efficient scavenging potency, and a cytotoxicity study proves the excellent cytocompatibility of AA-6-PCL loaded ß-CD/PCL SMPMs, which altogether herald their potential application in the study of the induced pluripotent stem cells.
Asunto(s)
Ácido Ascórbico/química , Portadores de Fármacos/química , Micelas , Poliésteres/química , Polímeros/síntesis química , Técnicas de Química Sintética , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/síntesis química , Células HEK293 , Humanos , Espectroscopía de Resonancia Magnética , Microscopía Electrónica de Transmisión , Nanosferas/ultraestructura , Tamaño de la Partícula , Polímeros/farmacocinética , beta-Ciclodextrinas/administración & dosificaciónRESUMEN
Supramolecular polymer micelles were prepared on basis of the inclusion complexation between cyclodextrin carbamates and cellulose derivatives in aqueous media. Cyclodextrin carbamates were synthesized by microwave-assisted method from cyclodextrin and urea. The urea modified cyclodextrin shows the higher yield than the physical mixture of urea/cyclodextrin in the micellization with cellulose derivatives. The supramolecular structure of the core-shell micelles was demonstrated by (1)H NMR spectra, TEM images, and fluorescence spectra. The drug release behavior of the supramolecular polymer micelles was evaluated using prednisone acetate as a model drug. The drug loaded micelles showed steady and long time drug release behavior. With these properties, the supramolecular polymer micelles are attractive as drug carriers for pharmaceutical applications.