Combined cross-linking treatments of bovine serum albumin gel beadlets for controlled-delivery of caffeine

Combined cross-linking agents (CCLA) of microbial transglutaminase (MTgase) and ribose were applied during production of bovine serum albumin gels via incubation and heating treatment, respectively. CCLA produced stronger gels with lower protein solubility in disruptive solvents (1% sodium dodecyl sulphate plus 1% β-mercaptoethanol) as compared to BSA gels (BSA/Control) or gels produced using single cross-linking agents (SCLA) of MTGase or ribose. The gels were then converted into dried beadlets containing caffeine following a freeze-drying process. In-vitro controlled-release of caffeine and swelling ratio studies of the beadlets in artificial saliva or simulated gastric fluid indicated that CCLA beadlets had the slowest release of caffeine and the lowest swelling ratio as compared to other beadlets. Scanning electron microscopy (SEM) data suggested that the improved release and the lower swelling ratio were mainly due to the denser network formed within the CCLA beadlets that had restricted the diffusion of caffeine and hampered the enzymatic breakdown of the matrix. The additional protein cross-linkings formed as a result of MTgase incubation and ribose-induced Maillard reaction could provide a delay action in releasing caffeine that potentially extend the duration of the action of the drug during ingestion.