期刊
INTERNATIONAL JOURNAL OF PHARMACEUTICS
卷 477, 期 1-2, 页码 408-415出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2014.10.040
关键词
Hybrid liposomes; Gold conjugates; Paclitaxel; Pharmacokinetics; Biodistribution; Anticancer efficacy
资金
- Natural Science Foundation of China [31470916]
- Program for New Century Excellent Talents in University [NCET-10-0816]
- Fundamental Research Funds for the Central Universities [JKQ2009026, JKP2011008]
- Priority Academic Program Development of Jiangsu Higher Education Institutions
- Open Project Program of MOE Key Laboratory of Drug Quality Control and Pharmacovigilance [MKLDP2013MS04]
Organic and inorganic drug delivery systems both demonstrate their own advantages and challenges in practical applications. Combining these two drug delivery strategies in one system is expected to solve their current issues and achieve desirable functions. In this paper, gold nanoparticles (GNPs) and liposomes have been chosen as the model systems to construct a hybrid system and investigate its performance for the tumor therapy of Paclitaxel (PTX). The thiol-terminated polyethylene glycol (PEG(400))-PTX derivative has been covalently modified on the surface of GNPs, followed by the encapsulation of PTX-conjugated GNPs (PTX-PEG(400)@GNPs) in liposomes. The hybrid liposomes solve the solubility and stability problems of gold conjugates and show high drug loading capacity. In vitro PTX release from the hybrid system maintains the similar sustained behavior demonstrated in its conjugates. Under the protection of a biocompatible liposome shell, encapsulated PTX shows enhanced circulation longevity and liver targetability compared to Taxol (R) and PTX-PEG(400)@GNPs suspension in the pharmacokinetic and biodistribution studies. These indicate that encapsulating drug-conjugated inorganic nanoparticles inside organic carriers maintains the superiority of both vehicles and improves the performance of hybrid systems. Although these attributes of hybrid liposomes lead to a better therapeutic capacity in a murine liver cancer model than that of the comparison groups, it shows no significant difference from Taxol (R) and conjugate suspension. This result could be due to the delayed and sustained drug release from the system. However, it indicates the promising potential for these hybrid liposomes will allow further construction of a compound preparation with improved performance that is based on their enhanced longevity and liver targetability of Paclitaxel. (C) 2014 Elsevier B.V. All rights reserved.
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