Block Copolymer Design for Camptothecin Incorporation into Polymeric Micelles for Passive Tumor Targeting
Abstract
Purpose Polymeric micelles were designed for targeting of a water-insoluble anticancer agent, camptothecin (CPT). Chemical structures of inner core segment were optimized to achieve high incorporation efficiency and stable CPT-loaded micelles.Methods Poly(ethylene glycol)-poly(beta-benzyl L-aspartate) block copolymer (PEG-PBLA) was synthesized. The PBLA chain was modified by alkaline hydrolysis of its benzyl group followed by esterification with benzyl, n-butyl, and lauryl groups. Incorporation of CPT into micelles was carried out by an evaporation method. The stability of drug-loaded micelles was studied by gel-permeation chromatography (GPC), and their in vitro release behaviors were analyzed.Results CPT was incorporated into polymeric micelles constructed by various block copolymers. Among the esterified groups, block copolymers with high benzyl ester contents showed high CPT loading efficiency and stable CPT-loaded micelles. In chain lengths, 5-27 Bz-69 showed the highest incorporation efficiency. In contrast, 5-52 Bz-67, which had a longer hydrophobic chain, showed low incorporation efficiency. Release of CPT from the micelles was dependent on the benzyl contents and chain lengths. Sustained release was obtained when the benzyl content was high.Conclusions CPT was successfully incorporated into polymeric micelles with high efficiency and stability by optimizing chemical structures of the inner core segment.
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Anticancer drugs encapsulated in polymeric micelles have shown better accumulation in the targeted site, reducing side effects on noncancerous tissues.
“Especially, anticancer drugs encapsulated in polymeric micelles have shown a better accumulation in the targeted site, thus reducing side effects on noncancerous tissues [46,47,48].”
From Recent Advances in Nanomicelles Delivery Systems. (2020) · cites this paper as [47]
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- Authors
- Opanasopit, P., Yokoyama, M., Watanabe, M., Kawano, K., Maitani, Y., & Okano, T.
- Affiliations
- Tokyo Women's Medical University (JP)
- Kanagawa Academy of Science and Technology (JP)
- Hoshi University (JP)
- Corresponding author
- Okano, Teruo
- Venue
- Pharmaceutical Research
- Published
- 2004-11
- Volume
- 21
- Issue
- 11
- Pages
- 2001-2008
- ISSN
- 0724-8741 (ISSN-L)
- 1573-904X
- OpenAlex
- W2030626376
- Cited by
- 141
- References
- 34
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 3 · 2023: 5 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 3 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 6
- FWCI
- 4.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Pharmaceutical Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Chemistry › Organic Chemistry › Advanced Polymer Synthesis and Characterization
- Keywords
- camptothecin, polymeric micelles, poly(β-benzyl-L-aspartate), drug incorporation efficiency, micelle stability, sustained drug release, passive tumor targeting
- MeSH terms
- Antineoplastic Agents, Phytogenic, Aspartic Acid, Biopolymers, Buffers, Camptothecin, Chemistry, Physical, Chromatography, Gel, Chromatography, High Pressure Liquid, Lactones, Micelles, Phosphates, Polyethylene Glycols, Proteins, Pyrenes, Drug Delivery Systems, Chemical Phenomena
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