The enhanced longevity and liver targetability of Paclitaxel by hybrid liposomes encapsulating Paclitaxel-conjugated gold nanoparticles

Liposomes and gold nanoparticles act as the model systems of organic and inorganic drug delivery systems, respectively, to construct a hybrid carrier for maintaining the superiority of both vehicles and improves the performance of Paclitaxel in the hybrid system. These hybrid liposomes provide a pro...

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Bibliographic Details
Published in:International journal of pharmaceutics 2014-12, Vol.477 (1-2), p.408-415
Main Authors: Bao, Quan-Ying, Zhang, Ning, Geng, Dong-Dong, Xue, Jing-Wei, Merritt, Mackenzie, Zhang, Can, Ding, Ya
Format: Article
Language:English
Subjects:
Animals
Anticancer efficacy
Antineoplastic Agents, Phytogenic - administration & dosage
Antineoplastic Agents, Phytogenic - pharmacokinetics
Antineoplastic Agents, Phytogenic - therapeutic use
Biodistribution
Biological Availability
Drug Carriers - chemistry
Drug Liberation
Gold - chemistry
Gold conjugates
Hybrid liposomes
Lipids - chemistry
Liposomes
Liver Neoplasms, Experimental - drug therapy
Liver Neoplasms, Experimental - metabolism
Male
Metal Nanoparticles - chemistry
Mice, Inbred ICR
Molecular Structure
Paclitaxel
Paclitaxel - administration & dosage
Paclitaxel - pharmacokinetics
Paclitaxel - therapeutic use
Pharmacokinetics
Polyethylene Glycols - chemistry
Rats, Sprague-Dawley
Sulfhydryl Compounds - chemistry
Tissue Distribution
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Summary:Liposomes and gold nanoparticles act as the model systems of organic and inorganic drug delivery systems, respectively, to construct a hybrid carrier for maintaining the superiority of both vehicles and improves the performance of Paclitaxel in the hybrid system. These hybrid liposomes provide a promising potential to further construct a compound preparation with improved performance based on their enhanced longevity and liver targetability of Paclitaxel. [Display omitted] 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 (PEG400)–PTX derivative has been covalently modified on the surface of GNPs, followed by the encapsulation of PTX-conjugated GNPs (PTX–PEG400@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® and PTX–PEG400@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® 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.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2014.10.040