Mucosal and systemic immune responses following mucosal immunisation of tetanus toxoid entrapped in lipid nanoparticles prepared by microwave reactor

• Published in: European journal of pharmaceutics and biopharmaceutics 2022-02, Vol.171, p.11-18
• Main Authors: Gebril, Ayman, Obeid, Mohammad A., Bennett, Ewan M., Pujol, Anairis, Chovel, Mario L., Mahy, Tatiana, Acevedo, Reinaldo, Ferro, Valerie A.
• Format: Article
• Language: English
• Subjects: Administration, Intranasal; Administration, Oral; And bilosomes; Animals; Drug Carriers; Immunization; Immunoglobulin G - immunology; Liposomes; Mice; Microwave reactor; Microwaves; Models, Animal; Mucosal immunisation; Mucous Membrane - metabolism; Nanoparticles; Niosomes; Tetanus toxin; Tetanus Toxoid - administration & dosage; Tetanus Toxoid - chemistry; Tetanus Toxoid - immunology; Tetanus Toxoid - pharmacokinetics
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2021.12.014

[Display omitted] In this study, the use of a microwave reactor, which allowed high input of energy into a pressurised system in a short period of time, was investigated for preparation of lipid nanoparticles (LNPs). The aim was to optimise the formulation process by reducing manufacturing time. Two types of LNPs were prepared; non-ionic surfactant vesicles (NISV) and bilosomes (modified NISV incorporating bile salts), with a model antigen (tetanus toxoid, TT) and the immune response induced after mucosal (nasal and oral, respectively) administration was assessed. The TT loaded LNPs were characterised in terms of particle size, size distribution, morphology, and entrapment efficiency. Immunisation was evaluated by lethal challenge with tetanus toxin in an animal model. The efficiency of vaccination was evaluated by measuring the anti-TT IgG antibody levels in the vaccinated animals. Bilosomes formed by this method showed an immunogen entrapment efficiency of ∼30% which was significantly (p