To achieve a good stealth property and to enhance the uptake by tumor cells, polymeric micelles containing a slightly negatively charged and zwitterionic corona at pH 7.4 (i.e., blood pH) and a positively charged surface at a slightly acidic pH (i.e., tumor extracellular pH) were prepared. The amphiphilic diblock copolymer which was used to prepare the polymeric micelles contains a hydrophilic block comprised of nonionic hydrophilic groups, negatively charged groups (carboxyl groups) and pH-triggered positive charge-generation groups (morpholino groups). The zeta potential of the micelles was found to increase as the pH decreased over the pH range covering the blood and tumor tissue pH ranges, and the corona of the micelles should contain zwitterionic groups. This could be due to that, in the pH range studied, more morpholino groups become protonated as the pH decreased, whereas the carboxyl groups were almost completely deprotonated to form carboxylate anions. Furthermore, by adjusting the molar ratio of morpholino to carboxyl groups, the zeta potential of the polymeric micelles was controlled to achieve a slightly negative value at pH 7.4. Thus, the combination of a slightly negatively charged surface and a zwitterionic corona suggests that these micelles would possess good stealth property. When the pH decreased from 7.4 to 6.8 or 6.5, the zeta potential value of the micelles became positive due to increased protonation of the morpholino groups. Correspondingly, the cellular uptake of the micelles by HeLa cells was enhanced. (C) 2015 Elsevier Ltd. All rights reserved.

Stearic acid-grafted and lipoic acid-grafted chitosan were prepared by dehydration condensation reaction between the amino groups of chitosan and the carboxyl groups of stearic acid and lipoic acid. The modified chitosan possessed amphiphilicity due to the incorporation of the hydrophobic groups. The pKa value of the residual amino groups of the modified chitosan increased from 6.6 to 6.8~7.1 after methylation. Nanoparticles of the modified chitosan were prepared in aqueous medium through ultrasonic dispersion. The Zeta potentials of the nanoparticles were positive in values, which indicated that the residual amino groups and their methylation derivatives were located on the surface of nanoparticles. The chitosan-based nanoparticles were reduced by dithiothreitol and oxidized with oxygen in air, the disulfide cross-linked structures were formed in the core of the final nanoparticles.

Amphiphilic diblock copolymers with poly(ethylene glycol) as the hydrophilic block and a random copolymer of n-butyl methacrylate or styrene and (N,N-diethylamino)ethyl methacrylate as the hydrophobic block were prepared by atom transfer radical polymerization (ATRP). Ibuprofen, a model drug that contains a carboxylic group and hydrophobic moiety, was loaded into micelles formed from the amphiphilic diblock copolymers by a combination of ionic interaction and hydrophobic effect. The loading capacity of ibuprofen in the micelles reached 60%. Loaded ibuprofen was released in a sustained fashion into media simulating gastric fluid (pH 1.6, 2h), small intestinal fluid (pH 7.4, 4h), and colon fluid (pH 6.7, 18h). Simulating the case of oral administration at 2doses per day, loaded ibuprofen was released almost linearly against time after the second dose in media simulating human gastrointestinal tract fluids.