Biochemistry and Pharmacology - Research Publications
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ItemNo Preview AvailableA Protective Vaccine Delivery System for In Vivo T Cell Stimulation Using Nanoengineered Polymer Hydrogel Capsules(AMER CHEMICAL SOC, 2009-11)Successful delivery of labile vaccine antigens, such as peptides and proteins, to stimulate CD4 and CD8 T cell immunity could improve vaccine strategies against chronic infections such as HIV and Hepatitis C. Layer-by-layer (LbL)-assembled nanoengineered hydrogel capsules represent a novel and promising technology for the protection and delivery of labile vaccine candidates to antigen-presenting cells (APCs). Here we report on the in vitro and in vivo immunostimulatory capabilities of LbL-assembled disulfide cross-linked poly(methacrylic acid) (PMA(SH)) hydrogel capsules as a delivery strategy for protein and peptide vaccines using robust transgenic mice models and ovalbumin (OVA) as a model vaccine. We demonstrate that OVA protein as well as multiple OVA peptides can be successfully encapsulated within nanoengineered PMA(SH) hydrogel capsules. OVA-containing PMA(SH) capsules are internalized by mouse APCs, resulting in presentation of OVA epitopes and subsequent activation of OVA-specific CD4 and CD8 T cells in vitro. OVA-specific CD4 and CD8 T cells are also activated to proliferate in vivo following intravenous vaccination of mice with OVA protein- and OVA peptide-loaded PMA(SH) hydrogel capsules. Furthermore, we show that OVA encapsulated within the PMA(SH) capsules resulted in at least 6-fold greater proliferation of OVA-specific CD8 T cells and 70-fold greater proliferation of OVA-specific CD4 T cells in vivo compared to the equivalent amount of OVA protein administered alone. These results highlight the potential of nanoengineered hydrogel capsules for vaccine delivery.
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ItemInfluence of size, surface, cell line, and kinetic properties on the specific binding of A33 antigen-targeted multilayered particles and capsules to colorectal cancer cells(AMER CHEMICAL SOC, 2007-09)There has been increased interest in the use of polymer capsules formed by the layer-by-layer (LbL) technique as therapeutic carriers to cancer cells due to their versatility and ease of surface modification. We have investigated the influence of size, surface properties, cell line, and kinetic parameters such as dosage (particle concentration) and incubation time on the specific binding of humanized A33 monoclonal antibody (huA33 mAb)-coated LbL particles and capsules to colorectal cancer cells. HuA33 mAb binds to the A33 antigen present on almost all colorectal cancer cells and has demonstrated great promise in clinical trials as an immunotherapeutic agent for cancer therapy. Flow cytometry experiments showed the cell binding specificity of huA33 mAb-coated particles to be size-dependent, with the optimal size for enhanced selectivity at approximately 500 nm. The specific binding was improved by increasing the dosage of particles incubated with the cells. The level of specific versus nonspecific binding was compared for particles terminated with various polyelectrolytes to examine the surface dependency of antibody attachment and subsequent cell binding ability. The specific binding of huA33 mAb-coated particles is also reported for two colorectal cancer cell lines, with an enhanced binding ratio between 4 and 10 obtained for the huA33 mAb-functionalized particles. This investigation aims to improve the level of specific targeting of LbL particles, which is important in targeted drug and gene delivery applications.
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ItemNo Preview AvailableP17-03. Nanoengineered layer-by-layer capsules as a novel delivery system for HIV vaccines(Springer Science and Business Media LLC, 2009-10-22)