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The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure

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Abstract

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.

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Acknowledgments

This work was supported by Portuguese Foundation for Science and Technology (FCT)—project PTDC/SAU-FAR/115044/2009, by the Center for Neuroscience and Cell Biology, University of Coimbra, PEst-C/SAU/LA0001/2013-014, by FCT fellowship DFRH—SFRH/BD/81350/2011, and by FCT in cooperation with Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, Brazil)—FCT/CAPES Proc.N.329/13.

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Authors and Affiliations

  1. Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde-Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Sandra Jesus & Olga Borges

  2. CNC, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-504, Coimbra, Portugal

    Sandra Jesus & Olga Borges

  3. Chemistry Department, Maringá State University, Paraná, Maringá, Brazil

    Elizangela H. Fragal, Adley F. Rubira & Edvani C. Muniz

  4. CQC, Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal

    Artur J. M. Valente

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  1. Sandra Jesus
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Correspondence to Olga Borges.

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Jesus, S., Fragal, E.H., Rubira, A.F. et al. The Inclusion of Chitosan in Poly-ε-caprolactone Nanoparticles: Impact on the Delivery System Characteristics and on the Adsorbed Ovalbumin Secondary Structure. AAPS PharmSciTech 19, 101–113 (2018). https://doi.org/10.1208/s12249-017-0822-1

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