Bovine serum albumin microspheres

In order to overcome the main limitations of the impregnation processes, connected to the limited solubility of the compounds in the supercritical fluids, Perman [68] proposed an alternative method. A supercritical impregnation process was coupled with a liquid solvent (preferentially water) to enhance the drug solubilization. The system composed of a liquid drug solution and the polymeric support was pressurized with the supercritical fluid. Consequently, the swelled polymer allows rapid diffusional transport of the solute into the polymeric substrate. In different examples, bovine serum albumin microspheres were impregnated with insulin, trypsin and gentamicin (see Table 9.9-5). 

Microspheres were prepared from carboxymethyl chitosan and alginate by emulsion phase separation. The encapsulated bovine serum albumin was... 

A unique method of formulating delivery systems based on starch/ PLA systems was studied (138). In that approach, the goal was to provide a better matrix for delivery of high molecular weight hydrophilic molecules. A hydrophilic material, starch, was combined through graft polymerization to PLA. The carbolactic polymers were then used to entrap bovine serum albumin in microspheres. 

While the major application of albumin microspheres is in the area of chemotherapy, there have been studies reporting the release of such varied compounds as 1-norgestrel (97), insulin (98), and hematoporphyrins (99) from bovine serum albumin, and the antibacterial sulfadiazine from ovalbumin (100). In general, burst phenomena are found for all systems studied. However, the results from the insulin study are worthy of note in that blood glucose levels were depressed for more than 14 days following the administration of insulin-containing BSA microspheres to diabetic rats. The smaller microspheres were absorbed by day 28 and the larger particles by day 56. 

Materials. Microspherical PGG glucan (Adjuvax, Alpha-Beta Technology, Worcester, MA) was prepared from Saccharomyces cereviseae strain R4 cells (11). Zymosan, cytochrome c (cyt c), bovine serum albumin (BSA), yeast alcohol dehydrogenase (ADH), Complete Freunds Adjuvant (CFA) and Incomplete Freunds Adjuvant (IFA) were purchased from Sigma Chemical Co. (St. Louis, MO). 

Zhang, F., Guo, J., Peng, X., Fi, Y. (2004) Preparation and release behaviour of carboxy-methylated chitosan/alginate microspheres encapsulating bovine serum albumin. Journal of Applied Polymer Science, 92, 878-882. 

In an interesting illustration of the first strategy, Sakaguchi and coworkers covalently attached hemoglobin to an aminopropyl silica particle and then polymerized organoalkoxysilanes on the surface of the hemoglobin-modified silica particle.85 The template was removed via treatment with oxalic acid.85 In more recent work, Zhang and coworkers utilized a similar approach. In their case, the sphere was made from the functionalized biopolymer, chitosan.86 The model template protein, bovine serum albumin, was covalently attached to the chitosan microsphere and then coated with a composite sol prepared from TEOS and an aminosilane.86... 

Jiang, W., and Schwendeman, S. P. (2001), Stabilization and controlled release of bovine serum albumin encapsulated in poly(D,L-lactide) and poly(ethylene glycol) microsphere blends, Pharm. Res., 18, 878-885. 

Bittner, B., Witt, C., Mader, K., and Kissel, T. (1999), Degradation and protein release properties of microspheres prepared from biodegradable poly(lactide-co-glycolide) and ABA triblock copolymers Influence of buffer media on polymer erosion and bovine serum albumin release, J. Controlled Release, 60, 297-309. 

The advantage of complex coacervates is that high payloads can be obtained. Chitosan/alginate coacervates have been reported to encapsulate up to 87% shark liver oil, which is rich in omega-3 fatty acids (Peniche et al. 2004). Microspheres of carboxymethyl chitosan/alginate hardened with calcium chloride have been used for encapsulation of up to 80% bovine serum albumin (Zhang et al. 2004). 

Tetanus toxoid (the vaccine for tetanus) encapsulated in polyester microspheres was produced for single-injection immunization. The entrapment efficiency of the protein vaccine was significantly improved by coencapsulation with excipients such as trehalose and y-hydroxypropyl cyclodextrin. However, these excipients did not impart stabilizing effect on tetanus toxoid. In contrast, bovine serum albumin was foimd to be the most prominent stabilizer for protein in the body after administration by injection. 

Coupling reactions of various proteins to the cellulose microspheres can be conducted by the CNBr activation method [29]. The proteins employed are bovine serum albumin (BSA), bovine immunoglobulin G(IgG), gelatin, tuftsin, and human serum fibronection (FN). 

Figure 8.30 Scanning electron micrographs of bovine serum albumin-loaded microspheres prepared from a ternary blend of poly( -caprolactone). Protein entrapment efficiency and mean particle size were 28.6% and 2.9 m respectively.

Polyanhydrides have also been investigated as protein carriers.f Poly(SA) and 20 80 CPH SA copolymer microspheres were foimd to conserve both the primary structure of the released protein [bovine serum albumin (BSA)] and the secondary structure of the encapsulated and released protein, and showed a sustained delivery for approximately 15 and 30 days, respectively. As the CPH content in the copolymer increased, the secondary structure of BSA was not conserved, as indicated by the steep decrease in the a-helix content. 

Rahman NA, Mathiowitz E. Localization of bovine serum albumin in double-walled microspheres. Journal of Controlled Release. January 8, 2004 94(1) 163-175. PubMed PMID 14684280. 

Al-Azzam W, Pastrana EA, Griehenow K. Co-lyophilization of bovine serum albumin (BSA) with poly(ethylene glycol) improves efficiency of BSA encapsulation and stability in polyester microspheres by a solid-in-oil-in-oil technique. Biotechnology Letters. 2002 24 1367-1374. 

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