L-Cystine dimethyl ester dihydrochloride

This study reports a series of novel amino acid based dual-responsive hydrogels. Prepared by a facile one-pot 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) coupling reaction, the solid content, structure, and mechanical behavior of hydrogels could be easily adjusted by changing the concentrations of the polymers and the crosslinkers. With pH-responsive anionic pseudo-peptides as backbones and disulfide-containing l-cystine dimethyl ester as crosslinkers, these hydrogels are able to collapse and form relatively compact structure at an acidic pH, while swelled and partly dissociated at a neutral pH. Further addition of dithiothreitol (DTT) facilitated complete degradation of hydrogels. The high loading efficiency, rapid but complete triggered-release, and good biocompatibility make these hydrogels promising candidates for oral delivery.

Oral administration is a noninvasive and convenient drug delivery route most preferred by patients. However, poor stability in the gastrointestinal tract and low bioavailability of hydrophobic drugs has greatly limited their oral administration. To address this problem, we report a pH-responsive, amphiphilic hydrogel drug carrier based on a pseudopeptide poly(l-lysine isophthalamide) (PLP) and poly(ethylene glycol) (PEG). The hydrogels were prepared by a simple N-(3-(dimethylamino)propyl)-N'-ethyl carbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) coupling reaction, and the cross-linking was confirmed by infrared spectroscopy and differential scanning calorimetry analyses. Because of the pH-responsive conformational alteration of PLP, the hydrogels were relatively hydrophobic and collapsed at acidic pH, but became hydrophilic and swollen at neutral pH. The amphiphilicity enabled the hydrogels to well retain and protect hydrophobic model drugs in the simulated gastric fluid, but efficiently release them in the simulated intestinal fluid. These results suggested that the pH-responsive amphiphilic hydrogels are promising candidates for oral delivery of hydrophobic drugs.

A pH and redox dual-responsive composite hydrogel was developed, which was formed from triblock copolymer PEG-SS-PCL-SS-PEG and Ag/AgO/carboxymethyl chitosan (CMCS) hydrogel inclusion complexes. Dithiodipropionic acid and poly(ethylene glycol) (PEG) were esterified to synthesize a hydrophilic segment PEG-SS-COOH polymer containing a disulfide bond, and ε-caprolactone is ring-opened in Ar atmosphere to obtain a hydrophobic segment HO-PCL-OH homopolymer. The PEG-SS-PCL-SS-PEG triblock polymers were prepared by reacting the two in a certain ratio, and spontaneously assembled into micelles in an aqueous solution. Ag/AgO/CMCS composite hydrogels with a pH and redox dual-responsive were prepared by dispersing aspirin-loaded micelles into an Ag/AgO/CMCS hydrogel network loaded with another hydrophilic drug ciprofloxacin hydrochloride (CIP). The results showed that the micelles had redox sensitivity due to the insertion of disulfide bonds, and had certain stability within 24 h without reducing substances. In vitro simulated drug release test of composite hydrogel showed that the hydrogel network swelled or degraded, the micelles were lysed, and the release of the drug was triggered when the composite hydrogels were exposed to the micro-environment with high pH or high DTT concentration. Therefore, this composite hydrogel could potentially be one of the candidate materials for the dual drug delivery system.