Characterization of surface NH3+Cl- groups on poly(styrene-co-Boc-aminostyrene) microspheres obtained by controlled acidic treatment.
Different samples of aminated latex of poly(styrene-co-Boc-aminostyrene) microspheres with mean diameters varying from 0.7 to 1.0 microm were prepared by dispersion copolymerization of styrene (ST) and Boc-aminostyrene (Boc-AMST). The copolymer compositions determined by nuclear magnetic resonance (1H NMR) were Boc-AMST/ST 6.9/93.1 mol/mol % (BOC7 sample) and Boc-AMST/ST 31.3/68.7 mol/mol % (BOC30 sample). The average molecular weights determined by gel permeation chromatography were 126 kDa (BOC7 sample) and 51 kDa (BOC30 sample). The latex containing NH-carbo-tert-butoxy groups (NH-Boc) were treated with 2 M HCl in isopropyl alcohol/water (1:1 vol/vol), at 50 degrees C for 3, 6, 9, 24, and 30 h, in order to control the extent of deprotection reaction of the NH-Boc. The deprotection reaction resulted in the formation of NH3+Cl- groups on the particle surfaces. The kinetic of the deprotection reaction was investigated by 1H NMR analyses and the yield varied from 20 to 40%. The resulting -NH3+Cl- groups on the microsphere surfaces were examined, in particular, by electron spectroscopy imaging (ESI) using an energy-filtered transmission electron microscope (EFTEM) that clearly demonstrated the presence of Cl on the particle surfaces. Scanning electron photomicrographs recorded for the above samples showed that the particle morphology was maintained after the acidic treatment.
Surface-functionalized polyurethane nanoparticles for targeted cancer therapy
Polymer nanoparticles (nps) have gained growing interest as carriers for anticancer drugs as they can target tumour tissues by both passive and active pathways. While the passive targeting mechanisms mainly rely on the small size of the carriers, active targeting requires surface modifications of the polymer core in order to introduce specific functionalities to actively recognize cancer cells. The present work proposes an innovative method for the preparation of surface-functionalized nps based on the use of biodegradable polyester- and polyester/ether-urethanes (PURs) embedding amino functionalities. Two polyurethanes were prepared, one based on just poly(ϵ-caprolactone) diol (PCL-PUR) and the other based on both PCL diol and poly(ethylene glycol) (PEG) (70/30 ratio, PCL-PEG-PUR). Nanoparticles of small size ranging between 150 and 200 nm and negative ζ potential (ranging from −18 mV to −27 mV) were obtained. Functional groups were exposed post nps preparation as confirmed by X-ray photoelectron spectroscopy, ninhydrin assay and 1H NMR, which evidenced a 24% tert-butyloxycarbonyl cleavage for PCL-PUR-NH2 nps and 29% for PCL-PEG-PUR-NH2 nps. The monoclonal antibody Herceptin (HER), which targets HER-2 receptors, was coupled through ethyl(dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) mediated chemistry. The optimal HER:NH2 ratio was determined to be 1:16 for the PEG-containing PUR and 1:8 for PCL-PUR. HER-nps maintained the intrinsic cytotoxicity of the antibody, as shown by the ca 50% decrease of HER-2-expressing HeLa cell viability. The results indicate that our protocol for surface functionalization of PUR nps, based on surface exposure of previously inserted functional groups followed by covalent coupling of biomolecules, is suitable for the preparation of nps for active recognition of target cells. © 2016 Society of Chemical Industry
Crosslinking of the inner poly(methyl methacrylate) core of poly(α-methylstyrene-b-methyl methacrylate) micelles in selective solvent: 2. Effect of polymer concentration
Abstract Core-corona type microgels composed of poly(methyl methacrylate) core and poly(α-methylstyrene) corona were synthesized from poly(α-methylstyrene-b-methyl methacrylate) in benzene/cyclohexane mixtures with varying polymer concentration. It was possible to synthesize soluble core-corona type microgels from the block copolymer with a small degree of polymerization ( DP ) in concentrated solution, when the micelle system turned from ‘open associated’ (stepwise associated) to ‘closed associated’ (mass action type) with increase of the polymer concentration. In the ‘open associated’ systems, the increase of the polymer concentration was the cause of inter-micelle crosslinking due to macrogelation and anomalization of the shape of the products.