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Poly(ethylene glycol) shell-sheddable nanomicelle prodrug of camptothecin with enhanced cellular uptake.
- Source :
-
Colloids and surfaces. B, Biointerfaces [Colloids Surf B Biointerfaces] 2013 May 01; Vol. 105, pp. 294-302. Date of Electronic Publication: 2013 Jan 16. - Publication Year :
- 2013
-
Abstract
- Surface modification of nanoparticles with poly (ethylene glycol) (PEG) shows poor cellular uptake, although it affords long circulation time and passive targeting potential to the tumor tissue. In this research, poly(ethylene glycol) shell-sheddable nanomicelle prodrug of camptothecin (CPT) was developed, in order to enhance the cellular uptake ability, achieve the passive targeting potential to tumor tissue and long circulation time, and to improve the stability of CPT in aqueous media. Firstly, the five-member rings in poly (L-succinimide) (PSI) were successively opened by the amino terminated disulfide-linked poly (ethylene glycol) monomethyl ether (mPEG-SS-NH2) and 6-aminocaproic acid to produce the graft copolymer of mPEG-SS-NH-g-PHAsp. And then, the resultant prodrug of mPEG-SS-NH-g-PHAsp-CPT was obtained by the esterification between carboxylic groups of mPEG-SS-NH-g-PHAsp and 20-OH of CPT. The prodrug was able to form spherical micelles in aqueous media because of its amphiphilic nature with average particle size of about 100nm measured by dynamic light scattering (DLS), suggesting its passive targeting potential to tumor tissue. Due to the detachment of PEG shell in the presence of dithiothreitol (DTT), the nanomicelle showed a tendency to aggregation, intense release of CPT, and enhanced cellular uptake ability. Also, the mPEG-SS-NH-g-PHAsp-CPT nanomicelle effectively protected the active lactone ring of CPT from hydrolysis under physiological condition. Compared with free CPT, mPEG-SS-NH-g-PHAsp-CPT nanomicelle showed essentially decreased cytotoxicity against L929 cell line in 24h, especially at high dosage, indicating its great potential as tumor tissue targeted prodrug.<br /> (Copyright © 2013 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Drug Carriers
Drug Compounding
Mice
Micelles
Nanoparticles administration & dosage
Tumor Cells, Cultured
Antineoplastic Agents, Phytogenic pharmacology
Camptothecin pharmacology
Fibrosarcoma drug therapy
Nanoparticles chemistry
Polyethylene Glycols chemistry
Prodrugs pharmacology
Surface-Active Agents chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1873-4367
- Volume :
- 105
- Database :
- MEDLINE
- Journal :
- Colloids and surfaces. B, Biointerfaces
- Publication Type :
- Academic Journal
- Accession number :
- 23384692
- Full Text :
- https://doi.org/10.1016/j.colsurfb.2013.01.014