期刊
JOURNAL OF POLYMER SCIENCE PART A-POLYMER CHEMISTRY
卷 57, 期 12, 页码 1322-1332出版社
WILEY
DOI: 10.1002/pola.29393
关键词
nanoparticles; drug delivery; polymers; polymerization
资金
- Stanford BIOX Interdisciplinary Initiatives Program (2016) Seed Grant
- Center for Human Systems Immunology
- Bill and Melinda Gates Foundation [OPP1113682]
- Hellman Faculty Scholarship
- PhRMA Foundation
- National Science Foundation [ECCS-1542152]
- Bill and Melinda Gates Foundation [OPP1113682] Funding Source: Bill and Melinda Gates Foundation
Nanoparticles are useful for the delivery of small molecule therapeutics, increasing their solubility, in vivo residence time, and stability. Here, we used organocatalytic ring opening polymerization to produce amphiphilic block copolymers for the formation of nanoparticle drug carriers with enhanced stability, cargo encapsulation, and sustained delivery. These polymers comprised blocks of poly(ethylene glycol) (PEG), poly(valerolactone) (PVL), and poly(lactide) (PLA). Four particle chemistries were examined: (a) PEG-PLA, (b) PEG-PVL, (c) a physical mixture of PEG-PLA and PEG-PVL, and (d) PEG-PVL-PLA tri-block copolymers. Nanoparticle stability was assessed at room temperature (20 degrees C; pH = 7), physiological temperature (37 degrees C; pH = 7), in acidic media (37 degrees C; pH = 2), and with a digestive enzyme (lipase; 37 degrees C; pH = 7.4). PVL-based nanoparticles demonstrated the highest level of stability at room temperature, 37 degrees C and acidic conditions, but were rapidly degraded by lipase. Moreover, PVL-based nanoparticles demonstrated good cargo encapsulation, but rapid release. In contrast, PLA-based nanoparticles demonstrated poor stability and encapsulation, but sustained release. The PEG-PVL-PLA nanoparticles exhibited the best combination of stability, encapsulation, and release properties. Our results demonstrate the ability to tune nanoparticle properties by modifying the polymeric architecture and composition. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1322-1332
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