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一种由聚酰胺-胺(PAMAM)G 3.5树枝状大分子和脂质体组成的新型嵌合药物递送纳米系统(chi-aDDnS)作为阿霉素的载体。体外药理学研究。

A new chimeric drug delivery nano system (chi-aDDnS) composed of PAMAM G 3.5 dendrimer and liposomes as doxorubicin's carrier. In vitro pharmacological studies.

作者信息

Gardikis Konstantinos, Fessas Dimitrios, Signorelli Marco, Dimas Konstantinos, Tsimplouli Chrisiida, Ionov Maksim, Demetzos Costas

机构信息

University of Athens, School of Pharmacy, Department of Pharmaceutical Technology, Panepistimioupolis, Zografou, 15771 Athens, Greece.

出版信息

J Nanosci Nanotechnol. 2011 May;11(5):3764-72. doi: 10.1166/jnn.2011.3847.

Abstract

Chimeric advanced Drug Delivery nano Systems (chi-aDDnSs) could be defined as mixed nanosystems due to the combination process of nanobiomaterials and can offer advantages as drug carriers. The role of the release modulator from the liposomal system is undertaken by the dendrimer molecules leading to new pharmacokinetic and, probably, pharmacological properties of the chimeric system. In this work, a conventional DOPC/DPPG liposomal system and a new chi-aDDnS composed of liposomes (DOPC/DPPG) incorporating PAMAM G3,5 has been developed, Doxorubicin (Dox) was loaded in the systems and the final formulations were lyophilized. The physicochemical (spectroscopic and calorimetric) investigation concerning the chi-aDDnS, revealed a strong interaction between both lipophilic and hydrophilic parts of the liposomal membrane and the dendrimer, with the induction of multiple energetic states. These states are probably the basis of higher Dox encapsulation and slower release rate compared to the respective conventional liposome. These results, in conjunction with the increase in TI observed in two investigated cancer cell lines (i.e., MB231 and MCF7), compared to the respective conventional liposomal system and to the free Dox, make this new chi-aDDnS the basic candidate for further in vivo investigations.

摘要

嵌合型先进药物递送纳米系统(chi-aDDnSs)由于纳米生物材料的组合过程可被定义为混合纳米系统,并且作为药物载体具有优势。脂质体系统中释放调节剂的作用由树枝状大分子承担,这导致了嵌合系统新的药代动力学以及可能的药理学特性。在这项工作中,已经开发了一种传统的二油酰磷脂酰胆碱/二棕榈酰磷脂酰甘油(DOPC/DPPG)脂质体系统以及一种由包含聚酰胺-胺(PAMAM)G3,5的脂质体(DOPC/DPPG)组成的新型chi-aDDnS,将阿霉素(Dox)载入系统并对最终制剂进行冻干。关于chi-aDDnS的物理化学(光谱和量热)研究表明,脂质体膜的亲脂性和亲水性部分与树枝状大分子之间存在强烈相互作用,并诱导出多种能量状态。与相应的传统脂质体相比,这些状态可能是更高的阿霉素包封率和更慢释放速率的基础。与相应的传统脂质体系统和游离阿霉素相比,这些结果与在两种研究的癌细胞系(即MB231和MCF7)中观察到的治疗指数(TI)增加相结合,使得这种新型chi-aDDnS成为进一步体内研究的基本候选物。

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