Delivery of PEGylated drugs from mucoadhesive formulations by pH-induced disruption of H-bonded complexes of PEG-drug with poly(acrylic acid)

We formed viscous, mucoadhesive gels by complexing PEGylated proteins with poly(acrylic acid) (PAA) at pH 3. These complexes dissociate at pH 7.4, and under this condition the PEGylated protein is released from the gel. We propose this system as a means for prolonged mucosal delivery of a PEGylated protein to nasal, ophthalmic or vaginal sites. In this paper we have studied the effect of the molecular weight of the PEG used in the PEGylated protein (5 kD, 20 kD and 40 kD PEG) and the effect of added free PEG (18.5 kD) on the in vitro release rate of the PEGylated protein from complexes with PAA. The PEGylated proteins we studied included papain, MW = 23.7 kD and pI 8.75, and soybean trypsin inhibitor (STI), MW = 20.1 kD and pI 4.6.