Preparation of core-crosslinked linear-dendritic copolymer micelles with enhanced stability and their application for drug solubilisation.
In this study we explore the preparation of core-crosslinked micelles of linear-dendritic methoxy-poly(ethylene glycol) (MPEG)-co-poly(ester-sulfide) (PES) polymers to improve the stability of such polymeric micelle systems against premature disintegration and drug release. A series of MPEG-PES copolymers were synthesised via stepwise reactions of acetylation and thiol-ene photoreaction. Surface tension measurement showed that the copolymers with ethenyl surface groups could self-associate in dilute aqueous solutions to form micelles. Crosslinking within the micelle cores in the presence of dithioerythritol (DTT) linker was initiated under UV radiation. The formation of core-crosslinked micelles was confirmed by HPLC in combination with charged aerosol detection (CAD). The copolymers were found to readily hydrolyse under acidic conditions due to the ester-containing dendrons. Drug solubilisation capacities of the micellar solutions were determined using griseofulvin as a poorly water-soluble model drug. The solubility of griseofulvin showed a 10-fold enhancement in 1% w/v micelle solution and increased with the concentration of the copolymers. Drug release studies indicated that a more sustained release of griseofulvin was achieved for the core-crosslinked micelles compared to the non-crosslinked micelles, attributable to greater stability of the crosslinked core structure. The findings of this study present a new pathway towards developing biodegradable polymeric nanocarriers.
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK. Electronic address: ZZhou2@uclan.ac.uk.
Zhengyuan
Z
Zhou
School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, UK.
Robert T
RT
Forbes
Leicester School of Pharmacy, De Montfort University, The Gateway, Leicester LE1 9BH, UK.
Antony
A
D'Emanuele
D003432:Cross-Linking Reagents / Q000737:chemistry / Q000528:radiation effects; D050091:Dendrimers / Q000737:chemistry* / Q000528:radiation effects; D004226:Dithioerythritol / Q000737:chemistry / Q000528:radiation effects; D065546:Drug Liberation; D006118:Griseofulvin / Q000737:chemistry; D008823:Micelles; D011091:Polyesters / Q000737:chemistry* / Q000528:radiation effects; D011092:Polyethylene Glycols / Q000737:chemistry* / Q000528:radiation effects; D011407:Propane / Q000031:analogs & derivatives / Q000737:chemistry / Q000528:radiation effects; D012995:Solubility; D014466:Ultraviolet Rays
C499598:2-hydroxy-1-(4-(hydroxyethoxy)phenyl)-2-methyl-1-propanone; D003432:Cross-Linking Reagents; D050091:Dendrimers; D008823:Micelles; D011091:Polyesters; D006118:Griseofulvin; D011092:Polyethylene Glycols; D004226:Dithioerythritol; C028210:monomethoxypolyethylene glycol; D011407:Propane
Charged aerosol detection; Core-crosslinking; Drug solubilisation; Linear-dendritic copolymers; Micellisation; Thiol-ene reaction