Poly(glutamic acid) poly(ethylene glycol) hydrogels prepared by photoinduced polymerization: Synthesis, characterization, and preliminary release studies of protein drugs.
A class of new biodegradable hydrogels based on poly(ethylene glycol) methacrylate-graft-poly(glutamic acid) and poly(ethylene glycol) dimethacrylate was synthesized by photoinduced polymerization. Because all the polymeric constituents were highly hydrophilic, crosslinking could be performed in aqueous solutions. This type of crosslinked hydrogel was prepared by modifying a select number of acidic side-groups on poly(glutamic acid) with poly(ethylene glycol) methacrylate. These modified chains were then crosslinked in the presence of poly(ethylene glycol) dimethacrylate under a photoinduced polymerization at a wavelength of 365 nm. Swelling experiments were conducted to study the crosslinking density, pH-responsive behavior, and degradation of the hydrogel. Results showed that the degree of swelling of this type of hydrogels increased as the crosslinker concentration (or density) was reduced. Because of the presence of acidic side chains on poly(glutamic acid), swelling behavior was found to be pH-responsive, increasing at high pH in response to the increase in the amount of ionized acidic side chains. The degradation rate of these hydrogels also varied with pH. More rapid degradation was observed under stronger alkaline conditions because of the hydrolysis of the ester bonds between the crosslinker and the polymer backbone. Practically useful degradation rates could be achieved for such hydrogels under physiological conditions. Drug release rates from these hydrogels were found to be proportional to the protein molecular weight and the crosslinker density; increasing at lower protein molecular weight or crosslinker density. The preliminary findings presented in this article suggest that this class of biodegradable hydrogels could be an attractive avenue for drug delivery applications. The specific photoinduced crosslinking chemistry used would permit hydrogels to be synthesized in existence of the entrapped macromolecular drugs including peptides, proteins, and cells. In addition, the rapid feature of this polymerization procedure along with the ability to perform hydrogel synthesis and drug loading in an aqueous environment would offer great advantages in retaining drug activity during hydrogel synthesis.
College of Pharmacy, The University of Michigan, Ann Arbor, Michigan 48109-1065, USA.
Zhiqiang
Z
Yang
Yuehua
Y
Zhang
Peter
P
Markland
Victor C
VC
Yang
D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000627:therapeutic use; D002021:Buffers; D016503:Drug Delivery Systems; D020100:Hydrogels / Q000138:chemical synthesis* / Q000627:therapeutic use; D007700:Kinetics; D010777:Photochemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011099:Polyglutamic Acid / Q000737:chemistry; D011506:Proteins / Q000008:administration & dosage* / Q000493:pharmacokinetics
D001672:Biocompatible Materials; D002021:Buffers; D020100:Hydrogels; D011506:Proteins; D011099:Polyglutamic Acid; D011092:Polyethylene Glycols