Optimization of PLG microspheres for tailored drug release.

Here we explore the opportunity to design and then produce tailored release of therapeutic drugs from microcapsules. By use of "building blocks," formed from well characterized microcapsule populations, an inverse design algorithm has been developed that provides an optimal (in a least squares sense) combination of building blocks to achieve a desired release history. Previously we have reported experiments and a well validated mathematical model for computing drug release histories from PLG microcapsules, and these form the backbone of the present optimization algorithm. To expand our available basis for finding useful optimal solutions, we also report work to validate the mathematical model for two different molecular weights. Thus, our building blocks comprise populations that differ by microsphere mean diameter, polydispersity, and polymer molecular weight, giving three separate parameters that effect drug release rate, and from which we build a foundation for our tailored release. Here we have taken a basis of six different microcapsule release systems, from which we build a tailored release history using constrained optimization to fit a prescribed release profile. Comparison of predicted release with measurements from the tailored microcapsule populations was found to produce excellent results, with correlation coefficients greater than 0.98. By way of demonstration, a triple pulse design is described that illustrates the power of the method.

On the mechanical properties of bovine serum albumin (BSA) adhesives.

Biological adhesives, natural and synthetic, are of current active interest. These adhesives offer significant advantages over traditional sealant techniques, in particular, they are easier to use, and can play an integral part in the healing mechanism of tissue. Thus, biological adhesives can play a major role in medical applications if they possess adequate mechanical behavior and stability over time. In this work, we report on the method of preparation of bovine serum albumin (BSA) into a biological adhesive. We present quantitative measurements that show the effect of BSA concentration and cross-linker content on the bonding strength of BSA adhesive to wood. A comparison is then made with synthetic poly(glycidyl methacrylate) (PGMA) adhesive, and a commercial cyanoacrylate glue, which was used as a control adhesive. In addition, BSA samples were prepared and characterized for their water content, tensile strength, and elasticity. We show that on dry surface, BSA adhesive exhibits a high bonding strength that is comparable with non-biological commercial cyanoacrylate glues, and synthetic PGMA adhesive. Tensile testing on wet wood showed a slight increase in the bonding strength of BSA adhesive, a considerable decrease in the bonding strength of cyanoacrylate glue, and negligible adhesion of PGMA. Tests performed on BSA samples demonstrate that initial BSA concentration and final water content have a significant effect on the stress-strain behavior of the samples.