Effect of polymer chemistry and fabrication method on protein release and stability from polyanhydride microspheres

Abstract

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.

Identifying Factors Controlling Protein Release from Combinatorial Biomaterial Libraries via Hybrid Data Mining Methods

“…The properties of polymers synthesized in these libraries were similar to those of conventionally synthesized polymers. 1,3,4,8,10,[22][23][24] The polymer molecular weights were in the range of 9000-16 000 g/mol with a polydispersity ranging between 1.5 and 3.0 (Table 1) as reported previously. Additionally, 1 H NMR chemical peaks were located in the correct positions and were of appropriate relative areas, indicating that the copolymers were pure, and were of the desired copolymer compositions.…”

“…This is in agreement with previous conventional and combinatorial studies in which release kinetics of other proteins were investigated. 1,3,10,24 4. MODELING 4.1.…”

“…[1][2][3][4] The drug release profiles from polyanhydride carriers can vary from days to months depending on the polymer chemistry, drug partitioning, and drug loading. The degradation via hydrolysis into their acidic monomers takes a period of months for poly(CPH), weeks for poly(SA), 5,6 and days for poly(CPTEG).…”

Combinatorial evaluation of in vivo distribution of polyanhydride particle-based platforms for vaccine delivery

“…Furthermore, they are capable of sustained antigen release and the activation of APCs, which contributes to the induction of high titer and high avidity antibody responses. 16,[18][19][20]22,24,25,[27][28][29] In the current work, only the IN nanoparticles dispersed rapidly throughout the body (Figures 1 and 2) and demonstrated prolonged residence in lung tissue (Figures 3 and 6). This enhanced persistence of nanoparticles in the lungs may provide a sufficient depot for antigen release, immune stimulation, and robust antibody production as observed previously.…”

“…12,13 Nanoparticles based upon copolymers of sebacic acid (SA), 1,6-bis-(p-carboxyphenoxy) hexane (CPH), and 1,8-bis-(p-carboxyphenoxy)-3,6-dioxaocatane (CPTEG) have been shown to exhibit tunable properties, including sustained antigen release kinetics, antigen stabilization, and immunomodulatory adjuvant behavior. [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] Recently in our laboratories, polyanhydride nanoparticles have been shown to induce less inflammation at administration sites than traditional adjuvants. 31 Additionally, histological evaluation revealed minimal toxicological effects and minimal adverse injection site reactions.…”