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Bioresponsive Controlled Drug Release Based on Mesoporous Silica Nanoparticles Coated with Reductively Sheddable Polymer Shell

Chang, Baisong, Chen, Dan, Wang, Yang, Chen, Yanzuo, Jiao, Yunfeng, Sha, Xianyi, Yang, Wuli·2013·Chemistry of Materials
DOI 10.1021/cm3037197
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Abstract

The design of bioresponsive controlled drug delivery systems is a promising approach in cancer therapy, but it still is a major challenge capable of optimum therapeutic efficacy, i.e. no premature drug leakage in blood circulation while having a rapid and complete release in tumor tissues. In this work, a kind of PEGylated core/shell structured composite nanoparticle was developed via precipitation polymerization, where a disulfide-cross-linked poly( N -vinylcaprolactam- co -methacrylic acid) (P(VCL- s - s -MAA)) polymer shell was created to act as sheddable thermo/pH-sensitive gatekeepers, and a carboxylic acid modified mesoporous silica nanoparticles (MSN-COOH) core was applicable as an accessible reservoir to encapsulate high drug doses. At physiological conditions, the P(VCL- s - s -MAA)-PEG shell underwent a distinct transition from a swollen state in pH 7.4 to a collapsed state in pH 5.0. Though sufficiently stable in water, composite nanoparticles were prone to fast dissociation and rupture when subjecting to 10 mM glutathione (GSH), due to the shedding of polymer walls through reductive cleavage of intermediate disulfide bonds, so that the polymer shell was active in moderating the diffusion of embedded drugs in-and-out of MSN channels. The cumulative in vitro release of DOX-loaded composite nanoparticles allowed a low trace of DOX diffusion below volume phase transition temperature (VPTT) and a significant release rate above its VPTT, while the most rapid and perfect…

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Metadata

Authors
Chang, B., Chen, D., Wang, Y., Chen, Y., Jiao, Y., Sha, X., & Yang, W.
Affiliations
  • State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University, No. 220 Handan Road, Shanghai 200433, China
  • Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education & PLA, Department of Pharmaceutics, School of Pharmacy, Fudan University, No. 826 Zhangheng Road, Shanghai 201203, China
Venue
Chemistry of Materials
Publisher
American Chemical Society (ACS)
Published
2013-02-12
Volume
25
Issue
4
Pages
574-585
ISSN
  • 0897-4756
  • 1520-5002
DOI
10.1021/cm3037197
Cited by
170
References
2
Language
en

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