Han Hee Dong, Choi Min Soo, Hwang Taewon, Song Chung Kil, Seong Hasoo, Kim Tae Woo, Choi Ho Suk, Shin Byung Cheol
Medicinal Science Division, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong, Daejeon 305-600, South Korea.
J Pharm Sci. 2006 Sep;95(9):1909-17. doi: 10.1002/jps.20646.
Temperature-sensitive liposomes (TS-liposomes) have been studied for chemotherapeutic purposes to enhance the release of anticancer drugs at tumor sites. In this study, we prepared poly(N-isopropylacrylamide-co-acrylamide) (PNIPAM-AAM) and polyethylene glycol (PEG)-modified TS-liposomes (PETS-liposomes). PETS-liposomes significantly increased in vitro drug release in serum compared with PEG-fixed or PNIPAM-AAM-modified liposomes. Furthermore, incorporation of both PNIPAM-AAM and PEG into PETS-liposomes enhanced the stabilities of liposomes in serum by inhibiting protein adsorption. In addition, to investigate the therapeutic efficacy of doxorubicin (DOX)-loaded PETS-liposomes, the in vivo antitumor activity of liposomes in combination with hyperthermia was evaluated in a B16F10 melanoma tumor-bearing mouse model. PETS-liposomes showed much higher levels of tumor growth inhibition than PEG-fixed or PNIPAM-AAM-modified TS-liposomes. Moreover, the antitumor activity of PETS-liposomes was enhanced significantly when they were administered in combination with hyperthermia. PETS-liposomes were found to be highly efficacious carriers for the in vivo delivery of anticancer drugs, and to have potential anticancer applications in combination with hyperthermia.
温度敏感脂质体（TS-脂质体）已被用于化疗目的，以增强抗癌药物在肿瘤部位的释放。在本研究中，我们制备了聚（N-异丙基丙烯酰胺-共-丙烯酰胺）（PNIPAM-AAM）和聚乙二醇（PEG）修饰的温度敏感脂质体（PETS-脂质体）。与PEG固定或PNIPAM-AAM修饰的脂质体相比，PETS-脂质体在血清中的体外药物释放显著增加。此外，将PNIPAM-AAM和PEG同时掺入PETS-脂质体中，通过抑制蛋白质吸附增强了脂质体在血清中的稳定性。另外，为了研究载有多柔比星（DOX）的PETS-脂质体的治疗效果，在B16F10黑色素瘤荷瘤小鼠模型中评估了脂质体与热疗联合的体内抗肿瘤活性。PETS-脂质体显示出比PEG固定或PNIPAM-AAM修饰的TS-脂质体更高水平的肿瘤生长抑制。此外，当PETS-脂质体与热疗联合给药时，其抗肿瘤活性显著增强。发现PETS-脂质体是用于体内递送抗癌药物的高效载体，并且在与热疗联合时具有潜在的抗癌应用。
