Characterizing poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCP) copolymer micelles for doxorubicin (DOX) delivery: effects of crosslinked of amine groups.
New amine-groups containing tri-block copolymers and micelles that consisting of poly(epsilon-caprolactone)-b-chitooligosaccharide-b-poly(ethylene glycol) (PCL-b-COS-b-PEG, PCP), were synthesized, characterized, and evaluated for delivering doxorubicin (DOX) with or without crosslinked amine groups by genipin. The characteristics of the PCP copolymers of Fourier-transform infrared spectrometry (FT-IR) verify the amine and ester groups of the COS and the PCL of the copolymers, respectively. 1H nuclear magnetic resonance (1H NMR) spectra verify the structures of the PCP copolymers consisting two PCL and PEG polymers reacted onto the COS block. In addition, gel permeation chromatography (GPC) determines the number average molecular weight of the tri-block copolymers (Mn) of approximately 11340 Da/mole. The PCP copolymers can self-assemble to form polymeric micelles at the critical micelle concentration (CMC) of 1.0 microM as determined by the UV-VIS absorption spectra. The mean diameter of the PCP micelles is 90 nm, as determined using a dynamic light-scattering (DLS) analyzer. Moreover, the zeta potentials of PCP micelles change from neutral to cationic state when pH of suspension mediums varied from 7.4 to 3.0. For evaluating delivery characteristics of hydrophobic DOX, it was loaded into PCP micelles with or without crosslinked by genipin. The burst release and release period of DOX for the crosslinked micelles are significantly reduced (P < 0.003, n = 3, for pH = 7.4) and sustained (e.g., 8 days), respectively, than those non-crosslinked ones (e.g., 4 days). In conclusion, new tri-block amine groups containing PCP copolymers are synthesized that can self-assemble as PCP micelles. After post-crosslinked amine groups of DOX loaded the micelles, they can effectively reduce the burst release and sustain the release of DOX at different pH dissolution mediums. Further applications of PCP copolymers and micelles for drug delivery can be explored in future.
Chung
Tze-Wen
TW
Department of Chemical Engineering, National Yunlin University of Science and Technology, Tou-Liu, Yunlin, 640 Taiwan, ROC.
Liu
Der-Zen
DZ
Hsieh
Jui-Hsiang
JH
Fan
Xian-Chan
XC
Yang
Jean-Dean
JD
Chen
Jui-Hsiang
JH
D000588:Amines / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D048271:Chitosan / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D003460:Crystallization / Q000379:methods*; D004058:Diffusion; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D046911:Macromolecular Substances; D008422:Materials Testing; D008823:Micelles; D008968:Molecular Conformation; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods; D009844:Oligosaccharides / Q000737:chemistry; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D013499:Surface Properties
D000588:Amines; D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D004337:Drug Carriers; D046911:Macromolecular Substances; D008823:Micelles; D009844:Oligosaccharides; D011091:Polyesters; C405621:poly(epsilon-caprolactone-co-ethylene oxide); D011092:Polyethylene Glycols; D004317:Doxorubicin; D048271:Chitosan