Development and biological evaluation of pNIPAM-based nanogels as vaccine carriers

• Published in: International journal of pharmaceutics 2023-01, Vol.630, p.122435-122435, Article 122435
• Main Authors: Soriano Pérez, Maria Laura, Funes, Javier Alejandro, Flores Bracamonte, Carolina, Ibarra, Luis Exequiel, Forrellad, Marina Andrea, Taboga, Oscar, Cariddi, Laura Noelia, Salinas, Facundo José, Ortega, Hugo Héctor, Alustiza, Fabrisio, Molina, Maria
• Format: Article
• Language: English
• Subjects: Animal model; Macrophages cells; pNIPAM nanogels; Vaccine carrier
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2022.122435

[Display omitted] •Thermoresponsive nanogeles are developed as vaccine platform.•Nanogels are internalized by macrophage cell line in absence of cytotoxicity.•Fluorescence of nanogels is detected in faeces after intranasal inoculation in mice.•OmlA-nanogels formulation produces detectable titer of OmlA-specific IgG antibodies. “Smart” nanogels are an attractive tool for the development of new strategies of immunization in veterinary medicine. Here, we reported the synthesis and physicochemical characterization of thermoresponsive nanogels based on poly(N-isopropylacrylamide) (pNIPAM) and theirin vitro, ex vivoand in vivo (mice model) performance. Smart nanogels of ca. 250 nm, with a transition temperature of 32 °C were obtained by precipitation polymerization. Assays to evaluatepNIPAM nanogels cytotoxicity were performed in different cell lines showing high biocompatibility (>70 %). The efficient internalization of the system was studied by confocal microscopy as well as flow cytometry. The ability to protect and deliver antigens was analyzed using the outer membrane lipoprotein A (OmlA), an important virulence factor ofActinobacillus pleuropneumoniae(App)cause of porcine pleuropneumonia. This lipoprotein was synthesized by recombinant technology and its technique was also described. The biodistribution ofpNIPAM nanogels administered intranasally was performedinvivo and ex vivo through Pearl Imaging System, which showed that nanogels were kept mostly in the lungs during the evaluated time. Besides, the efficacy of the proposal nanogel-based vaccine was studiedin vivoby measuring the antibody titers of BALB/c mice inoculated with OmlA encapsulated intopNIPAM nanogels compared to OmlA plus aluminum hydroxide adjuvant. The results proved the ability of nanogels to stimulate a humoral immune response. Therefore, we have demonstrated thatpNIPAM nanogels can be used as an efficient platform for vaccine nanocarriers.