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Cationic Polylactic Acid-Based Nanoparticles Improve BSA-FITC Transport Across M Cells and Engulfment by Porcine Alveolar Macrophages

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Abstract

This work described the development of a cationic polylactic acid (PLA)-based nanoparticles (NPs) as an antigen delivery system using dimethyldioctadecylammonium bromide (DDA) to facilitate the engulfment of BSA-FITC by porcine alveolar macrophages (3D4/2 cells) and heat-labile enterotoxin subunit B (LTB) to enhance the transport of BSA-FITC across M cells. The experimental design methodology was employed to study the influence of PLA, polyvinyl alcohol (PVA), DDA, and LTB on the physical properties of the PLA-based NPs. The size of selected cationic PLA NPs comprising 5% PLA, 5% PVA, and 0.6% DDA with or without LTB absorption was range from 367 to 390 nm with a polydispersity index of 0.26, a zeta potential of + 26.00 to + 30.55 mV, and entrapment efficiency of 41.43%. Electron micrographs revealed NPs with spherical shape. The release kinetic of BSA from the NPs followed the Korsmeyer-Peppas kinetics. The cationic PLA NPs with LTB surface absorption showed 3-fold increase in BSA-FITC transported across M cells compared with the NPs without LTB absorption. The uptake studies demonstrated 2-fold increase in BSA-FITC intensity in 3D4/2 cells with cationic NPs as compared with anionic NPs. Overall, the results suggested that LTB decreased the retention time of BSA-FITC loaded in the cationic PLA NPs within the M cells, thus promoting the transport of BSA-FITC across the M cells, and cationic NPs composed of DDA help facilitate the uptake of BSA-FITC in the 3D4/2 cells. Further studies in pigs with respiratory antigens will provide information on the efficacy of cationic PLA NPs as a nasal antigen carrier system.

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Funding

This study was supported by Research and Researchers for Industries (RRI, grant number PHD58I0037), and Agricultural Research Development Agency (Public Organization) (ARDA, grant number CRP5705010990). Furthermore, the partial funding was supported by Chulalongkorn University Special Task Force for Activation Research (CU-STAR): swine virus evolution and vaccine research (SVEVR).

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Authors and Affiliations

  1. Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Puwich Chaikhumwang, Jutarat Kitsongsermthon, Kasorn Manopakdee, Wanchai Chongcharoen & Angkana Tantituvanont

  2. Department of Veterinary Microbiology, Faculty of Veterinary Science, Chulalongkorn University, Bangkok, 10330, Thailand

    Dachrit Nilubol

  3. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Pithi Chanvorachote

  4. Cell-Based Drug and Health Product Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Pithi Chanvorachote & Angkana Tantituvanont

  5. Center of Excellence in Systems Biology, Faculty of medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Poorichya Somparn

  6. Center of Excellence in Immunology and Immune-mediated Diseases, Faculty of medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Poorichya Somparn

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  1. Puwich Chaikhumwang
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Chaikhumwang, P., Kitsongsermthon, J., Manopakdee, K. et al. Cationic Polylactic Acid-Based Nanoparticles Improve BSA-FITC Transport Across M Cells and Engulfment by Porcine Alveolar Macrophages. AAPS PharmSciTech 21, 134 (2020). https://doi.org/10.1208/s12249-020-01689-x

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