ovalbumin and caprolactone

This report extensively explores the benefits of including chitosan into poly-ε-caprolactone (PCL) nanoparticles (NPs) to obtain an improved protein/antigen delivery system. Blend NPs (PCL/chitosan NPs) showed improved protein adsorption efficacy (84%) in low shear stress and aqueous environment, suggesting that a synergistic effect between PCL hydrophobic nature and the positive charges of chitosan present at the particle surface was responsible for protein interaction. Additionally, thermal analysis suggested the blend NPs were more stable than the isolated polymers and cytotoxicity assays in a primary cell culture revealed chitosan inclusion in PCL NPs reduced the toxicity of the delivery system. A quantitative 6-month stability study showed that the inclusion of chitosan in PCL NPs did not induce a change in adsorbed ovalbumin (OVA) secondary structure characterized by the increase in the unordered conformation (random coil), as it was observed for OVA adsorbed to chitosan NPs. Additionally, the slight conformational changes occurred, are not expected to compromise ovalbumin secondary structure and activity, during a 6-month storage even at high temperatures (45°C). In simulated biological fluids, PCL/chitosan NPs showed an advantageous release profile for oral delivery. Overall, the combination of PCL and chitosan characteristics provide PCL/chitosan NPs valuable features particularly important to the development of vaccines for developing countries, where it is difficult to ensure cold chain transportation and non-parenteral formulations would be preferred.

Topics: Adsorption; Animals; Caproates; Chitosan; Drug Carriers; Female; Hydrophobic and Hydrophilic Interactions; Lactones; Mice; Mice, Inbred C57BL; Nanoparticles; Ovalbumin; Polymers; Protein Structure, Secondary

Serious challenges remain in immunotherapy, such as to effectively deliver antigens and non-invasively monitor biological processes. Therefore, we aim to design a useful nanocarrier for enhancing antigen-specific immune response and performing functional molecular imaging guided immunotherapy. To achieve this goal, ε-caprolactone modified polyethylenimine (PEI-CL) was prepared based on the ring-opening reaction. This novel macromolecule served as an optimal vehicle that efficiently bound ovalbumin (OVA) antigen forming a controlled nanostructure through electronic self-assembly and resulted in a substantially increased cellular uptake. In vivo, PEI-CL/OVA nanovaccine stimulated inflammatory cytokine production and promoted proliferation of OVA-specific T cells. Moreover, due to the unique chemical and physical properties, PEI-CL was demonstrated as a chemical exchange saturation transfer contrast agent for magnetic resonance imaging. In conclusion, the PEI-CL has synergistic advantages in the effective delivery of antigen and non-invasive imaging for tracking immunotherapeutic cells.

Topics: Animals; Antibodies; Antigens; Cancer Vaccines; Caproates; CD8-Positive T-Lymphocytes; Cell Proliferation; Cells, Cultured; Contrast Media; Cytokines; Fluorescent Dyes; Immunotherapy; Lactones; Macromolecular Substances; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred C57BL; Nanoparticles; Ovalbumin; Polyethyleneimine; RAW 264.7 Cells

A single dose vaccine formulation which induces both humoral and cell-mediated immune responses over a prolonged period would provide a potent weapon against infectious disease. We have used a water-in-oil-in-oil, solvent evaporation method for generating poly epsilon-caprolactone microparticles and tested their ability to induce an immune response against the model antigen ovalbumin. We hypothesized that the initial release of antigen from the surface of the poly epsilon-caprolactone microparticles would act as the priming dose and that the delayed release over the following months, due to diffusion from or break-down of the microparticles, would act as a boost to the immune response. Ovalbumin encapsulated in the poly epsilon-caprolactone microparticles was able to induce both antibody and cell-mediated immune responses. However our results suggest that the spontaneous release had little effect on the immune response. Despite this the response was maintained for at least 8 months following a single immunization. Both humoral and cell-mediated immune responses were induced in mice. This simple method of vaccine formulation offers a cost-efficient way to deliver antigen in a single dose to the immune system.

Topics: Animals; Antibody Formation; Biodegradation, Environmental; Caproates; Delayed-Action Preparations; Drug Carriers; Electrophoresis, Polyacrylamide Gel; Lactones; Lymphocyte Activation; Male; Mice; Microscopy, Electron, Scanning; Ovalbumin; Particle Size; Polymers; Vaccines