The effect of kinetic stability on biodistribution and anti-tumor efficacy of drug-loaded biodegradable polymeric micelles
Abstract
This study was aimed to investigate the effect of kinetic stability on biodistribution and antitumor efficacy of drug-loaded biodegradable polymeric micelles. Four diblock copolymers of acid- and urea-functionalized polycarbonate (i.e. PAC and PUC) and poly(ethylene glycol) (PEG) with the same polycarbonate length and two different PEG molecular weights (Mn: 5 kDa and 10 kDa), i.e. 5K PEG-PAC, 10K PEG-PAC, 5K PEG-PUC and 10K PEG-PUC, were synthesized via organocatalytic living ring-opening polymerization using methoxy PEG as a macroinitiator. These polymers were employed to prepare 5K PEG-PAC/5K PEG-PUC and 10K PEG-PAC/10K PEG-PAC mixed micelles via urea-acid hydrogen bonding. An amine group-containing anticancer drug, doxorubicin (DOX) was loaded into the mixed micelles via a self-assembly process. DOX-loaded 5K and 10K PEG mixed micelles had particle sizes of 66 and 87 nm respectively with narrow size distribution (polydispersity index: 0.12), and DOX loading levels were 28.9 and 22.8% in weight. DOX-loaded 5K PEG mixed micelles had greater kinetic stability than DOX-loaded 10K PEG mixed micelles due to stronger hydrophobicity of 5K PEG block copolymers. The results of in vitro release studies showed that DOX release was sustained without obvious initial burst release. The DOX-loaded mixed micelles effectively suppressed the proliferation of HepG2 and 4T1 cells. The in vivo studies conducted in a 4T1 mouse breast cancer model demonstrated that the mixed micelles were preferably transported to the tumor with the 5K PEG mixed micelles accumulating in the tumor more rapidly to a larger extent than 10K PEG mixed micelles, and DOX-loaded 5K PEG mixed micelles with greater kinetic stability inhibited tumor growth more effectively than free DOX and DOX-loaded 10K PEG mixed micelles without causing significant body weight loss or cardiotoxicity. The 5K PEG mixed micelles with sizes below 100 nm and narrow size distribution as well as excellent kinetic stability holds great potential as a delivery carrier for amine group-containing anticancer drugs.
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DLS can be used for evaluating micelles tendency to aggregate or disassembly over time.
“DLS can be used as well for evaluating micelles tendency to aggregate or disassembly over time as done by Moretton and collaborators [137] who determined the size of both blank and rifampicinloaded micelles composed of poly(epsilon-caprolactone)-b-poly (ethylene glycol)-poly(epsilon-caprolactone) (PCL-PEG-PCL) in filtered water at predetermined time intervals for one week after incubation of”
From Polymeric micelles in drug delivery: An insight of the techniques for their characterization and assessment in biorelevant conditions (2021) · cites this paper as [138]
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- Authors
- Ebrahim Attia, A. B., Yang, C., Tan, J. P. K., Gao, S., Williams, D. F., Hedrick, J. L., & Yang, Y.-Y.
- Affiliations
- Institute of Bioengineering and Nanotechnology (SG)
- Wake Forest University Health Sciences (US)
- IBM Research - Almaden (US)
- Corresponding author
- Yang, Chuan
- Hedrick, James L.
- Yang, Yi-Yan
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2013-04
- Volume
- 34
- Issue
- 12
- Pages
- 3132-3140
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W2060365720
- Cited by
- 131
- References
- 23
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 12 · 2020: 14 · 2019: 11 · 2018: 11 · 2017: 7 · 2016: 14 · 2015: 17 · 2014: 15 · 2013: 8
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biomaterials (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 › Materials Science › Polymers and Plastics › Dendrimers and Hyperbranched Polymers
- Keywords
- kinetic stability, tissue distribution, antitumor efficacy, doxorubicin, mixed micelles, drug release, tumor targeting, breast cancer, nanoparticle drug delivery, particle size and polydispersity, cardiotoxicity
- MeSH terms
- Antineoplastic Agents, Biocompatible Materials, Doxorubicin, Drug Carriers, Humans, Kinetics, Micelles, Neoplasms, Experimental, Particle Size, Tissue Distribution, Cell Line, Tumor, Hydrophobic and Hydrophilic Interactions
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