Polyion Complex Micelles Composed of All-TranS Retinoic Acid and Poly (Ethylene Glycol)-Grafted-Chitosan
Abstract
The goal of this study is to develop novel types of polyion complex micelles for the drug delivery to brain tumor. Methoxy poly(ethylene glycol) (mPEG)-grafted chitosan (CP) was synthesized in order to make polymeric micelles encapsulating all-trans retinoic acid (ATRA) based on polyion complex formation. Polyion complex micelles were found to have spherical shapes with sizes of about 50 approximately 200 nm. The loading efficiency of micelle was higher than 80% (w/w) for all formulations. 1H nuclear magnetic resonance (NMR) spectra confirmed the formation of polymeric micelles. The CP graft copolymer and ATRA have distinguishing peaks in their 1H NMR spectra. The specific peaks of ATRA disappeared in D2O or DMSO while it appeared at mixtures of D2O/DMSO, indicating that ATRA and chitosan formed ion complex inner-core. In the cell cytotoxicity study using U87MG cells in vitro, polyion complex micelles showed similar cytotoxicity to that of free ATRA. A migration test was performed to investigate the inhibition of tumor cell invasion in vitro. The results suggested that the polyion complex micelles was more effective at inhibiting tumor cell migration than free ATRA.
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Sustained release of RA for more than 1 month can be accomplished by encapsulating it into biodegradable microspheres and tuning release rate by adjusting polymer composition, by encapsulation in polyion complex micelles and adjusting polymer composition or drug content, or by encapsulation in liposomes.
“The sustained release of RA for more than 1 month can be accomplished by encapsulating it into biodegradable microspheres and tuning the release rate by adjusting polymer composition in the formulation61, by the encapsulation in polyion complex micelles62 and adjusting polymer composition or drug content, or by the encapsulation in liposomes49.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [62]
Because of the hydrophobicity of RA, the occurrence of a burst release in most formulations is negligible.
“Because of the hydrophobicity of RA, the occurrence of a burst release in most formulations is negligible44,47,51,63.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [47]
Polymeric micelles composed by methoxy-grafted chitosan and encapsulating ATRA were more effective at inhibiting glioblastoma cell line migration in vitro than the free agent.
“polymeric micelles composed by methoxy-grafted chitosan and encapsulating ATRA were more effective at inhibiting glioblastoma cell line migration in vitro than the free agent62.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [62]
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- Authors
- Jeong, Y.-I., Kim, S.-H., Jung, T.-Y., Kim, I.-Y., Kang, S.-S., Jin, Y.-H., Ryu, H.-H., Sun, H.-S., Jin, S., Kim, K.-K., Ahn, K.-Y., & Jung, S.
- Affiliations
- Chonnam National University (KR)
- Chonnam National University Hwasun Hospital (KR)
- Corresponding author
- Jung, Shin
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2006-11
- Volume
- 95
- Issue
- 11
- Pages
- 2348-2360
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2012176374
- Cited by
- 90
- References
- 37
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 2 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 1 · 2018: 4 · 2017: 3 · 2016: 9 · 2015: 8 · 2014: 8 · 2013: 5 · 2012: 6
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Keywords
- polyion complex micelles, all-trans retinoic acid, brain tumor drug delivery, tumor cell migration inhibition, U87 cells, cytotoxicity, tumor invasion
- MeSH terms
- Adsorption, Antineoplastic Agents, Brain Neoplasms, Carbohydrate Sequence, Cell Survival, Dimethyl Sulfoxide, Drug Carriers, Drug Compounding, Excipients, Glioma, Humans, Micelles, Molecular Sequence Data, Neoplasm Invasiveness, Magnetic Resonance Spectroscopy, Particle Size, Polyethylene Glycols, Mononuclear Phagocyte System, Tretinoin, Drug Delivery Systems, Cell Line, Tumor, Microscopy, Electron, Transmission, Chitosan, Nanoparticles
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