John M. Hilfinger

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The diverse secretory and absorptive functions of the intestinal epithelium are conducted by a mixed population of absorptive cells and mucus-producing goblet cells as the major cell types. In order to approach the main characteristics in an in vitro model, a coculture system of absorptive Caco-2 cells and mucus-secreting HT29-MTX cells was developed and(More)
The aim of this study was to synthesize amino acid ester prodrugs of 5-fluoro-2′-deoxyuridine (floxuridine) to enhance intestinal absorption and resistance to glycosidic bond metabolism. Amino acid ester prodrugs were synthesized and examined for their hydrolytic stability in human plasma, in Caco-2 cell homogenates, and in the presence of thymidine(More)
We examined the expression of the bacteriophage T4 nrdA and nrdB genes, which encode the alpha 2 and beta 2 subunits, respectively, of ribonucleoside diphosphate reductase, the first committed enzyme in the pathway of synthesis of the deoxyribonucleoside triphosphates. T4 nrdA, located 700 bp upstream from nrdB, has been shown previously to be transcribed(More)
Gemcitabine, a clinically effective nucleoside anticancer agent, is a polar drug with low membrane permeability and is administered intravenously. Further, extensive degradation of gemcitabine by cytidine deaminase to an inactive metabolite in the liver affects its activity adversely. Thus, strategies that provide both enhanced transport and high metabolic(More)
The study was designed to evaluate the effect of delayed release (DR) on absorption and bioavailability of intestinally metabolized drugs after oral dosing, using the HMG-CoA reductase inhibitor simvastatin, a CYP3A substrate, as a model drug. To target drug release and to assess regional gastrointestinal absorption of the CYP 3A substrate simvastatin from(More)
This report identifies formulation and processing factors that influence stability of viral preparations such as selection of appropriate buffer systems, cryoprotectants, and cooling rates. Adenovirus type 5 containing the lacZ marker gene was suspended in combinations of trehalose, sorbitol, sucrose, mannitol, glycine, CaCl2, and gelatin. X-gal stains of(More)
Purpose. To synthesize amino acid ester prodrugs of floxuridine (FUdR) and to investigate the effects of structure, stereochemistry, and site of esterification of promoiety on the rates of hydrolysis of these prodrugs in Caco-2 cell homogenates. Methods. Amino acid ester prodrugs of FUdR were synthesized using established procedures. The kinetics of(More)
As a part of a study of the role of bacteriophage T4-coded ribonucleoside diphosphate reductase in the switch-on and regulation of T4 DNA replication, we report the cloning and sequencing of the nrdA gene, coding for the alpha protein chain of the enzyme. The open reading frame of the nrdA gene begins 558 base pairs downstream of the 3' terminus of the td(More)
Purpose. Our goals are to establish an in vitro screening system and to evaluate a new approach in improving oral absorption of peptides and peptide-like drugs by overexpression of the human intestinal oligo-peptide transporter (hPepTl). This study characterizes the expression of hPepTl in human intestinal Caco-2 cells, rat intestinal epithelial cells(More)
Bioinformatics tools such as Perl, Visual Basic, Cluster, and TreeView were used to analyze public gene expression databases in order to identify potential enzyme targets for prodrug strategies. The analyses indicated that prolidase might be a desirable enzyme target based on its differential expression in melanoma cancer cell lines and its high substrate(More)