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用于癌症治疗的结合脂质体和树枝状大分子技术的新型药物递纳米系统(脂质体锁定树枝状大分子)。

New drug delivery nanosystem combining liposomal and dendrimeric technology (liposomal locked-in dendrimers) for cancer therapy.

机构信息

National Hellenic Research Foundation (NHRF), Institute of Organic and Pharmaceutical Chemistry, Athens, Greece.

出版信息

J Pharm Sci. 2010 Aug;99(8):3561-71. doi: 10.1002/jps.22121.

Abstract

Liposomal locked-in dendrimers (LLDs), the combination of liposomes and dendrimers in one formulation, represents a relatively new term in the drug carrier technology. LLDs undergone appropriate physicochemical investigation can merge the benefits of liposomal and dendrimeric nanocarriers. In this study generation 1 and 2 hydroxy-terminated dendrimers were synthesized and were then "locked" in liposomes consisting of DOPC/DPPG. The anticancer drug doxorubicin (Dox) was loaded into pure liposomes or LLDs and the final products were subjected to lyophilization. The loading of Dox as well as its in vitro release rate from all systems was determined and the interaction of liposomes with dendrimers was assessed by thermal analysis and fluorescence spectroscopy. The results were very promising in terms of drug encapsulation and release rate, factors that can alter the therapeutic profile of a drug with low therapeutic index such as Dox. Physicochemical methods revealed a strong, generation dependent, interaction between liposomes and dendrimers that probably is the basis for the higher loading and slower drug release from the LLDs comparing to pure liposomes.

摘要

脂质体锁定树枝状大分子(LLD)是将脂质体和树枝状大分子结合在一个制剂中的一个相对较新的术语,在药物载体技术中。经过适当的物理化学研究的 LLD 可以合并脂质体和树枝状纳米载体的优点。在这项研究中,合成了第一代和第二代羟基末端树枝状大分子,然后将其“锁定”在由 DOPC/DPPG 组成的脂质体中。将抗癌药物阿霉素(Dox)载入纯脂质体或 LLD 中,最后将所得产物进行冷冻干燥。测定了 Dox 的载药量及其从所有体系中的体外释放速率,并通过热分析和荧光光谱评估了脂质体与树枝状大分子的相互作用。就药物包封率和释放速率而言,这些结果非常有前景,这些因素可以改变药物的治疗谱,对于治疗指数低的药物(如 Dox),可以改变其治疗效果。物理化学方法揭示了脂质体和树枝状大分子之间强烈的、与代相关的相互作用,这可能是 LLD 比纯脂质体具有更高的载药量和更慢的药物释放的基础。

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