Polyion Complex Micelles Composed of All-TranS Retinoic Acid and Poly (Ethylene Glycol)-Grafted-Chitosan

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 form...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2006-11, Vol.95 (11), p.2348-2360
Main Authors: Jeong, Young-Il, Kim, Sang-Hyo, Jung, Tae-Young, Kim, In-Young, Kang, Sam-Suk, Jin, Yong-Hao, Ryu, Hyang-Hwa, Sun, Heung-Suk, Jin, Shuguang, Kim, Kyung-Keun, Ahn, Kyu-Youn, Jung, Shin
Format: Article
Language:English
Subjects:
Adsorption
all-trans retinoic acid
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Biological and medical sciences
Brain Neoplasms - drug therapy
brain tumor cell
Carbohydrate Sequence
Cell Line, Tumor
Cell Survival - drug effects
Chitosan - chemistry
Dimethyl Sulfoxide
Drug Carriers
Drug Compounding
Drug Delivery Systems
Excipients
General pharmacology
Glioma - drug therapy
Humans
ion complex
Magnetic Resonance Spectroscopy
Medical sciences
Micelles
Microscopy, Electron, Transmission
Molecular Sequence Data
Mononuclear Phagocyte System
Nanoparticles
Neoplasm Invasiveness
Particle Size
PEG-grafted chitosan
Pharmaceutical technology. Pharmaceutical industry
Pharmacology. Drug treatments
Polyethylene Glycols - chemistry
polymeric micelle
Tretinoin - administration & dosage
Tretinoin - chemistry
Tretinoin - pharmacology
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Summary: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 ∼ 200nm. 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.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.20586