Release characteristics of novel pH-sensitive p(HEMA-DMAEMA) hydrogels containing 3-(trimethoxy-silyl) propyl methacrylate

摘要

An amphiphilic hydrogel of poly(2-hydroxyethyl methacrylate) cross-linked with tetraethyleneglycol diacrylate (TEGDA) was synthesized to contain the hydrophobic monomer 3-(trimethoxy-silyl) propyl methacrylate (PMA) and the pH-responsive,hydrophilic monomer N',N'-dimethylaminoethyl methacrylate (DMAEMA).The gels were separately loaded with two biomolecular probes,insulin and protamine,via both physical entrapment and equilibrium imbibition methods.The release profiles for these biomolecular probes,possessing similar MW (5.7 and 4-6 kDa,respectively) but different pI's (5.3 and 10.0,respectively),were investigated with respect to variation in the pH of the bathing medium as well as the DMAEMA content,and the cross-link density of the hydrogel.Gels exhibited classical Fickian diffusion release profiles.For a typical gel composition 66:15:10:09 mol% (HEMA:DMAEMA:PMA:TEGDA),as the pH of the release media decreased from 7.3 to 4.0,the rateof release of both biomolecular probes increased.When loaded via entrapment,the insulin release rate increased ca.4-fold (1.0-3.7X10~(-7) cm~2 s~(-1)),whereas that of protamine increased 10-fold (0.3-3.3X10~(-7) cm~2 s~(-1)).When loaded by imbibition,the insulin diffusion coefficient increased 2-fold (3.8-7.2X10~(-7) cm~2 s~(-1)),whereas that of protamine increased 3-fold (1.9-5.5X10~(-7) cm~2 s~(-1)).The reduction of pH,through its protonation of the gel network,has a mode dramatic influence on protamine release,the result of its higher pI (10.0) compared to that of insulin (5.3).As the DMAEMA content of the hydrogel was increased from 0 to 20 mol%,the diffusion coefficient of protamine increased by ca.7-fold (1.7-12.2X10~(-7) cm~2 s~(-1)),whereas that of insulin increased only ca.2-fold (1.7-4.0X10~(-7) cm~2 s~(-1)).This differential release confirms the role of internal protonation in effecting the greater release of the protonated drug molecule.Increasing the TEGDA content from3 to 15 mol% reduced the diffusion coefficient ca.3-fold for insulin (1.6-0.5X10~(-7) cm~2 s~(-1)) and 5-fold for protamine (4.0-0.8X10~(-7) cm~2 s~(-1)).The final D_(ip) at 15 mol% TEGDA suggests that the smaller mesh size offsets any differential release that arises from protonation.The presence of PMA in the hydrogel formulation,which contributes additional cross-links by reason of the formation of siloxane macromers,did not change the usually observed Fickian diffusion mechanism.