P(HEMA)-based SPH vehicles for high molecular weight protein delivery

Abstract

Poly(2-hydroxyethyl methacrylate), p(HEMA), -based superporous hydrogels (SPHs) in interpenetrating network (IPN)/semi-IPN form were synthesized by radical polymerization with the incorporation of gelatin, acrylic acid (AA) and polyethylene glycol (PEG 600). They are called as p(HEMA) SPH, p(HEMA)-gelatin SPH-semi IPN, p(HEMA)-gelatin SPH-IPN, p(HEMA)-PEG SPH-semi IPN, p(HEMA-co-AA) SPH and p(HEMA-co-AA)-PEG SPH-semi IPN. SPHs reached equilibrium in ∼60 s with rapid swelling in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) due to the capillary effect. AA containing SPHs showed pH-dependent swelling and p(HEMA-co-AA)-PEG SPH-semi IPNs have the highest equilibrium swelling ratio. PEG containing SPHs, pHEMA-PEG and p(HEMA-co-AA)-PEG SPHs, showed great improvement in mechanical properties. Model proteins, bovine serum albumin (BSA) and fibrinogen (FG), were loaded into SPHs by solvent sorption in a very short time (<30 min) with very high capacities. Release profiles from SPHs indicated initial burst of proteins during the first 30 min followed by a completed release in 3 h for BSA and 6 h for FG. The results indicated that, especially p(HEMA-co-AA)-PEG SPH-semi IPNs with their pH-dependent high loading capacity without causing activity loss and fast release behavior can be considered as drug delivery vehicles especially in implantable systems for high molecular weight proteins.