Mucoadhesive drug carriers based on complexes of poly(acrylic acid) and PEGylated drugs having hydrolysable PEG-anhydride-drug linkages

We have designed a new mucoadhesive drug delivery formulation based on H-bo nded complexes of poly(acrylic acid) (PAA) or poly(methacrylic acid) (PMAA) with the poly(ethylene glycol) (PEG), of a (PEG)-drug conjugate. The PEGyl ated prodrugs are synthesized with degradable PEG-anhydride-drug bonds for eventual delivery of free drug from the formulation. In this work we have u sed indomethacin as the model drug which is PEGylated via anhydride bonds t o the PEG. The complexes an designed first to dissociate as the formulation swells in contact with mucosal surfaces at pH 7.4, releasing PEG-indometha cin, which then hydrolyses to release free drug and free PEG. We found that as MW of PAA increases, the dissociation rate of the complex decreases, wh ich results in decreased rate of release of the drug. On the other hand, th e drug release from PEG-indomethacin alone and from solid mixture of PEG-in domethacin+PAA was much faster than that from the H-bonded complexes. Due t o the differences in the thermal stability, PMAA complex exhibited slightly faster drug release than that of the PAA complex of comparable MW. These H -bonded complexes of degradable PEGylated drugs with bioadhesive polymers s hould be useful for mucosal drug delivery. (C) 2000 Elsevier Science B.V. A ll rights reserved.