New multidrug (dexamethasone and theophylline) PEG-conjugate: synthesis, in vitro release studies and intestinal permeability

A branched high-molecular weight multimeric PEG (MultiPEG), synthesized with a simple assembling procedure that devised the introduction of functional groups with divergent and selective reactivity, was employed as a drug carrier. Dexamethasone (DXM) and theophylline (THEO), examples of different but synergistic drugs, were covalently linked to the same MultiPEG unit. The hydrolytic stability of the mixed MultiPEG-conjugate (DXM-MultiPEG-THEO8) was evaluated at physiological pH, in an artificial gastric juice, in simulated duodenal fluids and in mouse plasma. The results demonstrated that this new branched PEG conjugate exhibited a slow degradation rate in simulated gastro-intestinal fluids, while in plasma a more rapid breakdown was observed. The permeation process across the intestinal membrane of the same macromolecular conjugate was investigated, mathematically discussed and interpreted according to “Fick’s law”.