Journal
AAPS PHARMSCITECH
Volume 15, Issue 1, Pages 213-222Publisher
SPRINGER
DOI: 10.1208/s12249-013-0041-3
Keywords
human serum albumin; nanoparticles; paclitaxel; self-assembly; targeted drug delivery
Categories
Funding
- Research Fund for the Doctoral Program of Higher Education of China [20110091120044]
- Natural Science Foundation of Jiangsu [BK2011572, BK2011539]
- National Natural Science Foundation [81202474, 30973651]
- Changzhou Special Project of Biotechnology and Biopharmacy [CE20105006]
- Science and Technology Support Program of Jiangsu Province [BE2010719]
- Postdoctoral Foundation [2012M521051]
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Protein-based nanomedicine plays an important role in tumor chemotherapy due to their merits in bioavailability, biocompatibility, biodegradability, and low toxicity. In this study, we developed a novel method of preparing human serum albumin (HSA) nanoparticles for targeted delivery of paclitaxel (PTX) to tumors. HSA-PTX nanoparticles (NPs-PTX) were fabricated via unfolding of HSA in appropriate solution to expose more hydrophobic domains and consequent self-assembling into nanoparticles with added PTX. Via this self-assembly method, a desirable particle size (around 120 nm), a high drug loading (>20%), and a high encapsulation efficiency (near 100%) were obtained. PTX dispersed as an amorphous state in NPs-PTX and the secondary structures of HSA were maintained. In a cytotoxicity study, NPs-PTX displayed an enhanced cytotoxicity in MCF-7 and A549 cells. Confocal microscopy and flow cytometry revealed that the uptake of NPs-PTX was mediated by secreted protein acidic and rich in cysteine and caveolar transport. In H22 tumor-bearing mice, NPs-PTX displayed an increasing and everlasting tumor distribution, leading to slower tumor growth and longer mice survival than PTX. Therefore, this novel self-assembly method offers a much easier method to prepare PTX nanoparticles, provides better antitumor efficacy in vitro and in vivo, and more importantly, sets up a delivery platform for other hydrophobic drugs to improve their effectiveness in cancer therapy.
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