Construction And Properties Of Temperature/pH Dual Responsive Nano Carriers Of Drug

’Smart’drug delivery systems, which can transport and deliver drug cargo at a selected location and a specific time, can enhance bioavailability of drugs and reduce their undesirable side-effect. Three’smart’drug delivery systems with methoxy polyethylene glycol (MPEG) and a thermal-responsible polymer as a mixed shell were prepared in this paper and their properties such as drug-loaded and release, cell toxicity were studied. MPEG shell could enhance the dispersity and imparted longevity to the drug delivery systems by preventing nonspecific protein adsorptions during their circulation in vivo and enhence the opportunity to arriving at diseased site. When the thermal-responsible chain was stretching, drug loading could be complete, while it collapsing, core-shell-corona structre which could be applied to suppress burst drug release was formed. The pH-responsible link of the core and the shell could achieve smart release. The results showed that the prepared drug delivery systems were stimulis-responsive and the drug relaese amout could be adjust by the ratio of MPEG to thermal-responsible polymer. They were nontoxic and the DOX-loaded nanoparticles could be successfully internalized into cancer cells. Therefore, this kind of drug delivery systems are very promising candidates for improvements in drug delivery systems. The details are as follows:1. Poly(N-vinylcaprolactam)-b-poly lactic acid (PNVCL-b-PLA) and methoxy poly (ethylene glycol)-b-poly lactic acid (MPEG-b-PLA) block polymers were synthesized by ring openning polymerization of lactide (LA) using macroinitiators MPEG and hydroxyl-terminated poly(N-vinylcaprolactam) (PNVCL-OH), which was prepared by polymerization of N-vinylcaprolactam (NVCL) using azobisisobutyronitrile (AIBN) as a initiator and mercaptoethanol as a chain transfer agent. A mixed-shell polymeric micelles (MSMs) were prepared by self-assembly of PNVCL-b-PLA and MPEG-b-PLA in water at room temperature with PLA as the core and MPEG/PNVCL as the mixed shell. The structures of the micelles were confirmed and the drug loading and release behavor using DOX as a model drug were studied. The release rate of DOX at 25 ℃ was faster than that at 37 ℃ at pH 7.4. The drug release rate could be adjusted by the ratio of MPEG to PNVCL in the mixed shell. The low cytotoxicity of the mixed micelles was confirmed by MTT assay against HCT-116 cells and the DOX-loaded nanoparticles could be successfully internalized into cancer cells.2. Diaminotriazine-terminated poly(s-caprolactone) (DAT-PCL), uracil-terminated methoxy poly(ethylene glycol) (MPEG-U) and uracil-terminated poly(N-vinylcaprolactam) (PNVCL-U) were prepared and their structures were confirmed. The supermolecular mixed-shell polymeric micelles (SMSMs) were prepared by self-assembly of DAT-PCL, MPEG-U and PNVCL-U in water at room temperature with PCL as the core and MPEG/PNVCL as the mixed shell.’H NMR and FT IR showed that the micelles (MPEG-U or PNVCL-U…DAT-PCL) were formed based on multiple hydrogen bonding interactions. Dynamic light scattering (DLS) indicated that all of the micelles exhibit unimodal size distribution and the sizes of micelle increased with the increase of the proportion of hydrophobic segment. The morphologies of micelles visualized by transmitance electric micrography (TEM) are spherical. The SMSMs were therm/pH dual responsive. Studies on the in vitro drug release showed that the release rate of DOX at pH 5.0 was faster than that at pH 7.4 and that at 25 ℃ was faster than that at 37 ℃. The drug release rate could be adjusted by the ratio of MPEG-U…DAT-PCL2 to PNVCL-U…DAT-PCL2. The low cytotoxicity of the mixed micelles was confirmed by MTT assay against BGC-823 cells and the DOX-loaded nanoparticles could be successfully internalized into cancer cells.3. Mesoporous silica nanoparticles (MSNs) were prepared. To abtained thermo/pH dual responsive drug delivery system, two kinds of polymers, including methoxy poly(ethylene glycol) (MPEG) and thermo-responsive poly(N-isopropyl acrylamide) (PNIPAM), were covalently attached to the outlets of the mesopores, through a highly acid-sensitive benzoic-imine linker. Their structures were confirmed and the drug loading and release behavor from the hybrid-MSNs using DOX as a model drug were studied. The results showed that the release rate of DOX at pH 5.0 was faster than that at pH 7.4 and that at 25℃ was faster than that at 37℃. The drug release rate could be adjusted by the ratio of MPEG to PNIPAM in the shell. The low cytotoxicity of the MSNs was confirmed by MTT assay against HCT-116 cells and the DOX-loaded nanoparticles could be successfully internalized into cancer cells.