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There are many important diseases whose treatment could be improved by delivering a therapeutic protein to the colon, for example, Clostridium difficile infection, ulcerative colitis and Crohn's Disease. The goal of this project was to investigate the feasibility of colonic delivery of proteins using multiparticulate beads.In this work, bovine serum albumin (BSA) was adopted as a model protein. BSA was spray layered onto beads, followed by coating of an enteric polymer EUDRAGIT® FS 30 D to develop a colonic delivery system. The secondary and tertiary structure change and aggregation of BSA during spray layering process was examined. The BSA layered beads were then challenged in an accelerated stability study using International Council for Harmonization (ICH) conditions. The in vitro release of BSA from enteric coated beads was examined using United States Pharmacopeia (USP) dissolution apparatus 1.No significant changes in the secondary and tertiary structure or aggregation profile of BSA were observed after the spray layering process. Degradation of BSA to different extents was detected after storing at 25°C and 40°C for 38 days. Enteric coated BSA beads were intact in acidic media while released BSA in pH 7.4 phosphate buffer.We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

Allergy and asthma are among the most common chronic diseases of childhood. Cockroach allergy is an important contributor to asthma morbidity, with a prevalence of 17 to 41%. Immunotherapy has been shown to be an effective treatment for other allergies that contribute to asthma, but several factors have limited its use for cockroach allergy. In this work, a sublingual immunotherapy (SLIT) formulation of orally dissolving thin film has been developed for the treatment of hypersensitivity to the German cockroach Bla g 2 allergen. The formulation allows for the incorporation of up to 25 μg/film of the allergen protein, and the film's mucoadhesiveness prolongs the effect of the allergen with the potential for enhanced efficacy. The potency and dose uniformity of the SLIT formulation were characterized by enzyme-linked immunosorbent assay (ELISA), and other physicochemical properties were evaluated by spectroscopic or mechanistic methods. The films were uniform in weight and thickness, and demonstrated substantial physical strength to allow easy manipulation during manufacturing and dosing. The dosage uniformity, in vitro disintegration and in vitro dissolution profiles of the films were within the acceptance criteria in the United States Pharmacopeia. The developed SLIT methodology possesses the potential to significantly improve immunotherapy for both food and inhalant allergies in adults and children.