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Core-crosslinked Poly(N-isopropylacrylamide-co-N,N-dimethylacrylamide)-b-Poly(ε-caprolactone) Micelles for Paclitaxel Controlled Release

Author: ZhangLei
Tutor: CaiQing
School: Beijing University of Chemical Technology
Course: Materials Science and Engineering
Keywords: P(NIPAAm-co-DMAAm) PCL thermosensitive core-crosslinked micelle paclitaxel
CLC: O631.3
Type: Master's thesis
Year: 2010
Downloads: 112
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Abstract


The sizes of polymeric micelles are generally less than 100nm. With the characteristics of nano-materials they are being researched as drug carriers in recent years. Polymeric micelles have the features of structural, stability, excellent tissue permeability, long residence time in vivo, and they also can effectively reach the target drugs. To develop new kind of polymeric micelles for target drug delivery and to decrease the initial burst release are the major two issues in this area. In this study, we produced thermo-sensitive nanoscale micelles with different core-crosslinkings, and their drug release behaviors were studied. Main tasks are listed as follows:1, In this study we used the two-step polymerization to produce the poly(N-isopropylacrylanide-co-N,N-dimethylacrylanide)-b-poly(-capr olactone) block copolymers (P (NIPAAm-co-DMAAm)-b-PCL). At first with mercaptoethanol as chain transfer agent, and by adjusting the monomer ratio of NIPAAm and DMAAm, the molecular weight and lower critical solution temperature (LCST) of P (NIPAAm-co-DMAAm) can be controlled. Then, caprolactones were ring-polymerized by the hydroxyl endgroup of P (NIPAAm-co-DMAAm) by using stannous octotate as catalyst to obtain hydroxyl-terminated P (NIPAAm-co-DMAAm)-b-PCL. By reacting with acryloyl chloride, the hydroxyl endgroups were changed into acryloyl endgroups.2, Hydroxyl-terminated and acryloyl-terminated of P(NIPAAm-co-DMAAm)-b-PCL were mixed to get polymeric micelles with the different degrees of core crosslinking. The hydrophobic drug was paclitaxel loaded in the micelles, and the temperatures of the drug release tests were setting at 37℃or 43℃. The results showed that the drug release from the micelles exhibifed a certain themosentivity. The cross-linking degrees had a more remarkable effect paclitaxel release. With the cross-linking degree of increase, the release of paclitaxel slowed down, and the initial burst release was reduced. The results of the present study show that the micelles based on thermosentive P(NIPAAm-co-DMAAm)-b-PCL with a LCST around-40℃maybe able to realize a thermo-responsive release behavior at temperatures above and below LCST. Furthermore, the core-crosslinking method can be used to increase the stability of micelles and adjust the drug release rates. With further deep investigation, this kind of thermosensitive micelles can have potential use as carriers for hydrophobic anticancer agents targeted for solid tumor therapy with local hyperthermia therapy.

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CLC: > Mathematical sciences and chemical > Chemistry > Polymer chemistry ( polymer ) > Polymer physics and physical chemistry of polymers > The chemical nature of polymers
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