ovalbumin and sebacic-acid

The development of high-throughput techniques and combinatorial libraries can facilitate rapid synthesis and screening of biomaterial-based nanocarriers for drug and vaccine delivery. This study describes a high-throughput method using an automated robot for synthesizing polyanhydride nanoparticles encapsulating proteins. Polyanhydrides are a class of safe and biodegradable polymers that have been widely used as drug and vaccine delivery vehicles. The robot contains a multiplexed homogenizer and has the capacity to handle parallel streams of monomer or polymer solutions to synthesize polymers and/or nanoparticles. Copolymer libraries were synthesized using the monomers sebacic acid, 1,6-bis( p-carboxyphenoxy)hexane, and 1,8-bis( p-carboxyphenoxy)-3,6-dioxactane and compared to conventionally synthesized copolymers. Nanoparticle libraries of varying copolymer compositions encapsulating the model antigen ovalbumin were synthesized using flash nanoprecipitation. The amount of the surfactant Span 80 was varied to test its effect on protein encapsulation efficiency as well as antigen release kinetics. It was observed that, although the amount of surfactant did not significantly affect protein release rate, its presence enhanced protein encapsulation efficiency. Protein burst and release kinetics from conventionally and combinatorially synthesized nanoparticles were similar even though particles synthesized using the high-throughput technique were smaller. Finally, it was demonstrated that the high-throughput method could be adapted to functionalize the surface of particle libraries to aid in the design and screening of targeted drug and vaccine delivery systems. These results suggest that the new high-throughput method is a viable alternative to conventional methods for synthesizing and screening protein and vaccine delivery vehicles.

Topics: Biocompatible Materials; Decanoic Acids; Dicarboxylic Acids; Drug Delivery Systems; Drug Liberation; Hexanes; Hexoses; Kinetics; Nanoparticles; Ovalbumin; Polyanhydrides; Proteins; Small Molecule Libraries

The release kinetics and stability of ovalbumin encapsulated into polyanhydride microspheres with varying chemistries were studied. Polymers based on the anhydride monomers sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis (p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were utilized. Microspheres were fabricated using two non-aqueous methods: a solid/oil/oil double emulsion technique and cryogenic atomization. The studies showed that the two fabrication methods did not significantly affect the release kinetics of ovalbumin, even though the burst release of the protein was a function of the fabrication method and the polymer chemistry. Antigenic stability of ovalbumin released from microspheres prepared by cryogenic atomization was studied by western blot analysis. These studies indicate that the amphiphilic CPTEG:CPH polyanhydrides preserved protein structure and enhanced protein stability by preserving the immunological epitopes of released protein.

Topics: Biocompatible Materials; Blotting, Western; Decanoic Acids; Dicarboxylic Acids; Drug Carriers; Drug Stability; Hexanes; Kinetics; Microspheres; Ovalbumin; Particle Size; Polyanhydrides; Polyethylene Glycols; Proteins; Solubility