A Multiparticulate Delivery System for Potential Colonic Targeting Using Bovine Serum Albumin as a Model Protein

Abstract

Purpose 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. Methods 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. Results 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. Conclusion We showed the feasibility of delivering proteins to colon in vitro using multiparticulate system.

Formulation and Manufacturing of Solid Dosage Forms

“…Biopharmaceutical products including protein therapeutics have been increasingly developed in the past decade. Jiang et al developed a multiparticulate system for colonic delivery of bovine serum albumin (BSA) (13). In this study, BSA was spray layered onto beads and coated using an enteric polymer EUDRAGIT® FS 30 D. Results showed BSA beads were protected from acidic media while BSA was released in pH 7.4 phosphate buffer, which demonstrated the feasibility to develop colonic delivery systems for proteins.…”

“…Lubach and Hau utilized solid state nuclear magnetic resonance spectroscopy (NMR) to examine drug-excipient interactions and phase behavior in indomethacin-Eudragit E ASDs (7). 13 C and 15 N solid-state NMRs were used to determine changes in local structure and protonation state, while 1 H T 1 and T 1ρ relaxation measurements were used to probe miscibility and phase behavior of the dispersions. This study highlights the prowess of using ss-NMR to understand solidstate properties of ASDs.…”

Electroanalytical Biosensors for Circulating Tumor DNA Detection—A Brief Review

“…The biomolecular recognition elements of ctDNA biosensor can be categorized into enzymes, nucleic acids, simulated enzymes, immune substances, etc [11] . Biomolecular probes can be fixed on the surface of biosensor by physical adsorption [17] , covalent bonding [18][19][20] , embedding [21][22][23] , self-assembled membrane [24][25][26] , affinity [27,28] and other methods, as shown in Fig. 2.…”

In Vitro Methods to Study Colon Release: State of the Art and An Outlook on New Strategies for Better In-Vitro Biorelevant Release Media

“…This is especially true for a range of inflammatory diseases of the GI-tract such as Crohn’s disease and Ulcerative colitis [ 1 , 2 , 3 , 4 , 5 , 6 ] but also for other diseases in the colon that would benefit from a local treatment including colon cancer [ 7 , 8 ], enteric nematodes [ 9 ] and enzyme replacement therapies [ 10 ]. Other areas of interest are colon delivery of proteins and peptides [ 11 , 12 ], probiotic bacteria [ 13 , 14 ] and microbiota replacement therapies [ 15 ]. In these cases, formulations are employed aiming at colon-targeted delivery and at the same time avoiding release in the upper GI-tract.…”