Development and evaluation of a protein based delivery system for targeting drug delivery to the stomach

Development of “controlled oral drug delivery system” to produce more reliable absorption and improve bioavailability and efficacy of drug delivery has been a long-standing goal in the field of pharmaceutical design. The major focus of my thesis research is to determine the feasibility of localized drug delivery to the stomach using a protein based delivery vehicle, zein, which has both hydrophobic and hydrogel properties. The ability to improve delivery of therapeutic agents locally to the stomach via a bioadhesive system would have important clinical application in area such as the treatment of peptic ulcer diseases, because a more convenient dosing schedule can lead to improved patient compliance and better therapeutic outcome.; Bioadhesiveness of the zein system as compared to other polymers (polyesters and polyanhydrides) were evaluated based on in vitro tensiometric technique utilizing the Cahn microbalance, as well as in vivo GI transit time studies in rats via radiologic determination of the radioopaque BaSO₄ loaded polymers post intra-gastric feeding. We showed that incorporation of tetracycline and bismuth may increase bioadhesiveness of zein. In addition, zein showed retention in the stomach at up to 44.5 hrs during in vivo transit time studies and appeared to coat the mucosa based on its ability to spread along the surface. Release characteristics of antibiotic tetracycline from the various systems were evaluated under different in vitro conditions and showed that zein formulations produced favorable release profiles with smaller burst effect and higher amount of released tetracycline at subsequent time points. This release also appeared to be loading dependent as smaller burst effect was seen with higher loading. Tetracycline may produce this effect by increasing the hydrophobicity of zein. Finally, the utility of the zein formulations in delivering active drug locally to the stomach was assessed via tetracycline assay based on both spectrophotomic and diffusion zone techniques. Although the final in vivo feeding studies did not show a dramatic difference between the unencapsulated tetracycline and the two zein formulations (spray-dried zein, solvent removal zein microspheres), statistically significant results were seen at 3 hrs with zein formulations showing that they were more effective in delivering tetracycline.