Lo Chun-Liang, Huang Chun-Kai, Lin Ko-Min, Hsiue Ging-Ho
Department of Chemical Engineering, National Tsing Hua University, 101, Section 2 Kuang Fu Road, Hsinchu 300, Taiwan, ROC.
Biomaterials. 2007 Feb;28(6):1225-35. doi: 10.1016/j.biomaterials.2006.09.050. Epub 2006 Nov 9.
A novel mixed micelle that comprised of poly(N-isopropylacrylamide-co-methacrylic acid)-graft-poly(D,L-lactide) (P(NIPAAm-co-MAAc)-g-PLA) with methoxy poly(ethylene glycol)-b-poly(D,L-lactide) (mPEG-b-PLA) was developed for application in cancer therapy. The mixed micelle had an multi-functional inner core of P(NIPAAm-co-MAAc)-g-PLA to enable intracellular drug delivery and an extended hydrophilic outer shell of mPEG to hide the inner core. Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicates that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of graft copolymer were efficiently screened by mPEG. From the drug release study, the mPEG-PLA diblock copolymer in mixed micelles slightly affected the functionalities of the P(NIPAAm-co-MAAc)-g-PLA graft copolymer; the graft copolymer still exhibited pH- and thermo-sensitivities in this core-shell structure. A change in pH deformed the structure of the inner core from that of aggregated P(NIPAAm-co-MAAc), causing the release of a significant quantity of doxorubicin (Dox) from mixed micelles. Clear differences between free Dox and Dox-mixed micelles were observed using confocal laser scanning microscopy (CLSM). This study presents not only a new micelle structure for a graft-diblock copolymer system, but also a method for overcoming some of the limitations on biomaterials used in intravenous injection.
一种新型混合胶束被开发用于癌症治疗，它由聚（N-异丙基丙烯酰胺-共-甲基丙烯酸）-接枝-聚（D，L-丙交酯）（P（NIPAAm-co-MAAc）-g-PLA）与甲氧基聚（乙二醇）-b-聚（D，L-丙交酯）（mPEG-b-PLA）组成。该混合胶束具有多功能的P（NIPAAm-co-MAAc）-g-PLA内核以实现细胞内药物递送，以及延伸的亲水性mPEG外壳来隐藏内核。混合胶束在牛血清白蛋白（BSA）溶液中的稳定性分析表明，二嵌段共聚物mPEG有效地保护了混合胶束上的BSA吸附，因为接枝共聚物的疏水基团被mPEG有效地屏蔽了。从药物释放研究来看，混合胶束中的mPEG-PLA二嵌段共聚物对P（NIPAAm-co-MAAc）-g-PLA接枝共聚物的功能影响较小；在这种核壳结构中，接枝共聚物仍表现出pH和温度敏感性。pH的变化使内核结构从聚集的P（NIPAAm-co-MAAc）变形，导致大量阿霉素（Dox）从混合胶束中释放。使用共聚焦激光扫描显微镜（CLSM）观察到游离Dox和Dox混合胶束之间存在明显差异。这项研究不仅提出了一种用于接枝-二嵌段共聚物体系的新胶束结构，还提出了一种克服静脉注射中生物材料某些局限性的方法。
