Jochen Kalbe

Development of buccal drug delivery systems based on a thiolated polymer.

The purpose of the present study was to investigate the benefit of thiolated polymers (thiomers) for the development of buccal drug delivery systems. L-Cysteine was thereby covalently attached to polycarbophil (PCP) mediated by a carbodiimide. The resulting conjugate displayed 140.5+/-8.4 microM thiol groups per gram polymer. Disintegration studies were carried out with tablets based on unmodified polymer and conjugated polymer, respectively. Due to the formation of disulfide bonds within the thiolated polymer, the stability of matrix-tablets based on this polymer was strongly improved. Additionally tensile studies were carried out, which were in good correlation with further results obtained by mucoadhesion studies, using the rotating cylinder method. These results showed that tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding control. Moreover, the enzyme inhibitory properties of polymers were evaluated as well. Thiolated PCP increased the stability of the synthetic substrate for aminopeptidase N-leu-p-nitroanilide (N-leu-pNA) and the model drug leucin-enkephalin (leu-enkephalin) against enzymatic degradation on buccal mucosa. Due to the use of thiolated polymers also a controlled drug release for leu-enkephalin was guaranteed over a time period for more than 24 h. Results of the present studies suggest that thiolated polymers represent a very useful tool for buccal delivery of peptide drugs.

In vivo activities of the new anthelmintic depsipeptide PF 1022A.

Abstract PF 1022A is a member of a new class of cyclic depsipeptides with antiparasitic activity. Following in vitro and laboratory animal studies it was tested for its anthelmintic efficacy in companion and livestock animals against a wide spectrum of intestinal nematodes and lungworms. Studies were carried out in rats, dogs, horses, sheep, and cattle. Animals were either naturally or experimentally infested. The efficacy of PF 1022A was investigated against the following parasite species: Strongyloides ratti and Nippostrongylus brasiliensis in rats, Ancylostoma caninum in dogs, small strongyles (cyathostomes) in horses, Trichostrongylus colubriformis and Haemonchus contortus in sheep, and Dictyocaulus viviparus in cattle. Doses varied from 1 to 10 mg/kg body weight for oral, subcutaneous or intravenous application in companion and livestock animals. High degrees of efficacy were found in all the above-cited examinations, and no clinical signs of intolerability were observed.