Entrapment of bioactive compounds within native albumin beads: II. Effects of rate and extent of crosslinking on microbead properties

The rate of crosslinking of serum albumin is affected by several parameters such as pH, buffer concentration, and the ratio of serum albumin to glutaraldehyde concentration. Selection of experimentally controllable variables makes it possible to control crosslinking rate at room temperature to form a serum albumin microbead with an appropriate extent of crosslinking that provides both structural integrity and biodegradability. It was confirmed that serum albumin concentrations of 200 mg/ml of sodium phosphate buffer solution (pH = 7.5, 10 mM) and 1% glutaraldehyde is a very favorable combination using a mixing time of around 20 sec before adding to oil phase to form an emulsion. A curing time of around 30 min is then used. Drug loading efficiency is crosslink rate-controlled. Mixing time also affects drug loading efficiency since it fixes the time for potential partitioning of drug out of the aqueous phase. The biodegradable character of the microbeads has been shown and it appears to be a function of the amount of serum albumin and glutaraldehyde used.