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Double network (DN) hydrogels have shown favorable toughness and strength and been harnessed as scaffolding materials in tissue engineering, particularly, mineralized DN hydrogels may be potential scaffolds in bone tissue engineering. In this paper, DN hydrogels were fabricated from poly(ethylene glycol) diacrylate (PEGDA) and methacrylated poly(γ-glutamic acid) (mPGA). This DN hydrogel not only showed excellent mechanical properties but also good cytocompatibility as evidenced by the characterizations in terms of swelling ratio, mechanical strength/modulus, and cytotoxicity. Further, the DN hydrogels were subjected to mineralization in simulated body fluid, during which hydroxyapatite or analogues formed within the DN hydrogels; the DN hydrogels may be potentially harnessed as bone tissue engineering scaffold.

Tumor microenvironment-responsive nano drug delivery vehicles are gaining mounting attention in the field of biomedical sciences. The hypoxic response of the tumorous cells due to very low partial pressure of oxygen (some time less than 2.5 mm of Hg) in the tumor tissues makes hypoxia-responsive drug delivery system as the more appealing in cancer chemotherapy. Based on these considerations, we synthesized hypoxia-responsive polymeric materials methoxy poly (ethylene glycol)-block-poly (glutamic acid)-graft-6-(2-nitroimidazole) hexyl amine (mPEG-b-PLG-g-NID) by conjugation of the hydrophobic nitro imidazole derivative (NID)[6-(2-nitroimidazole) hexyl amine] with the pendant carboxylic group of poly (ethylene glycol)-block-poly (L-glutamic acid)(mPEG-b-PLG). The structure and degree of substitution were confirmed by proton NMR, FTIR, and UV-Vis spectroscopy. The degree of substitution was found to enhance with the increase in NID to polymer ratio. The hypoxia response of the material was evaluated by UV-Vis spectroscopy and zeta potential measurements. Doxorubicin was hydrophobically encapsulated in the micellar core of the hypoxia-responsive nanoparticles. The drug-loaded micelles showed faster release in hypoxic condition as compared to normoxic conditions. Moreover, the developed polymeric system was found non-toxic to MCF-7 cell line, thus suggesting its biocompatibility and suitability as drug delivery device.

An in situ-formed hydrogel was synthesized by enzymatic cross-linking of poly(γ-glutamic acid)-tyramine conjugates (PGA-Tyr) using horseradish peroxidase (HRP) and hydrogen peroxide (H2O2). The gelation time ranged from 25 s to 5 min was accomplished by tuning the concentration of HRP, H2O2/Tyr molar ratio and the degree of substitution (DS) of Tyr groups. The storage modulus (G'), cross-link density, and mesh size can be tailored by controlling the H2O2/Tyr ratio and DS. The rheological analysis indicated that the storage modulus (G') can be tailored from approximately 40 to over 1100 Pa with the increasing H2O2/Tyr ratio and DS. The bovine serum albumin (BSA) was used as model protein and encapsulated into the hydrogel during the enzyme-mediated cross-linking reaction. Controlled release of BSA in vitro from the PGA-Tyr hydrogel was obtained. The release rate and cumulative release amount of encapsulated BSA were manipulated by controlling the H2O2/Tyr ratio and DS. More than 90% of encapsulated BSA was released from the hydrogel with low cross-link density and lager mesh size in 60 h, while only 68% of BSA was released from the hydrogel with high cross-link density and small mesh size. The results indicated that the PGA-Tyr hydrogel is a promising material for the controlled release of therapeutic protein or peptides.

This study focused on the preparation and evaluation of nanoparticles made of alkyl esters of microbial poly(gamma-glutamic acid) (PGGA) to be used as drugs and proteins carrier and delivery systems. Racemic PGGA of bacterial origin was fully methylated or partially esterified to render non-water-soluble polymers. A set of co-polymers containing poly(glutamic acid) and ethyl, hexyl, dodecyl and octadecyl glutamate units with alkyl contents of 50 and 75% was prepared. Spherical nanoparticles with a diameter of 200-250 nm and a narrow distribution were generated from the alkylated polymers by the precipitation-dialysis method. These nanoparticles readily degraded hydrolytically upon incubation in simulated physiological medium at a rate dependent on the alkylation degree and the length of the alkyl group. All these nanoparticles were able to encapsulate efficiently erythromycin. Those made of carboxyl containing polyglutamates were also effective to load alpha-chymotrypsin. The release of such compounds from nanoparticles upon incubation proceeded essentially following the same profile that is followed in the hydrolysis of the corresponding substrate polymers. The loss of enzyme activity of the incubated protein diminished significantly upon encapsulation in these systems.