Doxorubicin (DOX) is a widely used chemotherapeutic drug for the treatment of several types of cancers, which has limitation in clinical applications because of severe heart toxicity. Herein, to reduce the fast clearance from the blood system and the severe systemic toxicity caused by the nonspecific protein adsorption, a pH-sensitive drug delivery system with higher drug conjugated content was prepared by conjugating DOX onto hydroxyethyl starch (HES) with a pH-sensitive hydrazone bond. In normal physiological environment, the release of DOX conjugated onto HES was slight which could be neglected without any side effect. However, in an acidic environment mimicking the tumor microenvironment, this pH-sensitive hydrazone linkage provided a controlled and sustained release of DOX over a period of more than 3 days. The conjugates had good biocompatibility, long circulation, and lower cytotoxicity, which could efficiently be transferred into HeLa and HepG2 cells and release the conjugated drug. Based on these promising properties, these HES–DOX conjugates outline the significant potential for future biomedical application in the controlled release of antitumor drugs. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42778.

As drug delivery systems, stimuli-responsive polymer micelles hold great potential in cancer chemotherapeutics to improve therapeutic efficiency and eliminate organism adverse effects. Here, pH-sensitive polymeric micelles based on dextran-g-benzimidazole were designed and used for intracellular anticancer drug delivery. The anticancer drug doxorubicin (DOX) was effectively loaded into the micelles via hydrophobic interactions. In vitro release studies demonstrated that the release of loaded DOX was greater and faster under acid conditions such as in carcinomatous areas (pH < 6.8) than in physiological conditions (pH 7.4). MTT assays and flow cytometric analyses showed that DOX-loaded micelles had higher cellular proliferation inhibition towards HeLa and HepG2 cells than pH-insensitive controls. These pH-sensitive micelles with significant efficiency for intracellular drug release will be beneficial to the future of in vivo biomedical applications. © 2014 Society of Chemical Industry

A series of pH-dependent thermo-sensitive hydrogels for oral insulin delivery is designed and synthesized. In contrast to normal pH- and thermo-sensitive hydrogels, the release of oral insulin from them is mainly controlled by the adjustable swelling ratios in gastric and intestinal juice with their variable pH sensitivity. The release behavior of loaded insulin depends on the swelling/shrinking transition because of the changing LCST at different pH values. The hydrogels presented are composed of PNIPAAm chains and PMAA segments and are prepared with the biodegradable acryloyl-poly(ϵ-caprolactone)-2-hydroxylethyl methacrylate as a crosslinker. The biodegradation rates of the hydrogels are directly related to their PMAA content. In vitro release of insulin from the hydrogels is investigated and the release profiles indicate that the smart hydrogels are of great promise in pH–temperature oral insulin delivery systems.

Microgel particles were prepared, made of hydroxypropylcellulose-graft-(acrylic acid) (HPC-g-AA) and acrylic acid(AA). The particles undergo reversible volume phase transitions in response to both pH and temperature changes while keeping the inherent properties of PAA and HPC-g-AA. Dynamic light scattering measurements reveal that the average hydrodynamic radius and hydrodynamic radius distributions of the microgel particles depend on temperature and pH. The microgels exhibit excellent pH sensitivity and a higher swelling ratio at higher pH in aqueous solution. In vitro release study shows that the amount of insulin released from the microgels is less at pH = 1.2 than at pH = 6.8. The results indicate that the resultant microgels seem to be of great potential for intelligent oral drug delivery. Copyright © 2012 Society of Chemical Industry

In this article, novel smart hydrogels based on biodegradable pH sensitive poly(L-glutamic acid-g-2-hydroxylethyl methacrylate) (PGH) chains and temperature-sensitive hydroxypropylcellulose-g-acrylic acid (HPC-g-AA) segments were designed and synthesized. The influence of pH and temperature on the equilibrium swelling ratios of the hydrogels was discussed. The optical transmittance of the hydrogels was also changed as a function of temperature, which reflecting that the HPC-g-AA part of the hydrogels became hydrophobic at the temperature above the lower critical solution temperature (LCST). At the same time, the LCST of the hydrogels had a visible pH-dependent behavior. Scanning electron microscopic analysis revealed the morphology of the hydrogels before and after enzymatic degradation. The biodegradation rate of the hydrogels was directly related to the PGH content and the pH value. The in vitro release of bovine serum albumin from the hydrogels were investigated. The release profiles indicated that both the HPC-g-AA and PGH contents played important roles in the drug release behaviors. These results show that the smart hydrogels seem to be of great promise in pH–temperature oral drug delivery systems. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2011