Nano spray dryer for vectorizing α-Galactosylceramide in polymeric nanoparticles: a single step process to enhance invariant Natural Killer T lymphocyte responses

Publication date: Available online 7 May 2019Source: International Journal of PharmaceuticsAuthor(s): Michelangelo Bauwelz Gonzatti, Maria Eduarda Perrud Sousa, Ariane Simões Tunissi, Renato Arruda Mortara, Adriano Marim de Oliveira, Natália Neto Pereira Cerize, Alexandre de Castro KellerAbstractThe recognition of α-galactosylceramide (αGC), a high-affinity CD1d antigen, by the invariant Natural Killer T (iNKT) lymphocytes results in potent immunostimulatory responses that have been exploited in advanced cancer patients. Therefore, to improve αGC biological activity, several studies vectorized this agonist in PLGA and/or PEG-based nanoparticles. Despite promising findings, these approaches require several steps, from organic solvent decontamination through extrusion in membrane systems. Using a nano spray dryer, we vectorized αGC into a cationic copolymer (dimethylaminoethyl methacrylate, butyl methacrylate and methyl methacrylate - DBM) in a single step process, free of organic solvent. This methodology allowed the production of stable αGC-vectorized nanoparticles (DBM+αGC) with a more potent biological activity than the free agonist. DBM nanoparticles improved in vivo αGC loading into the CD1d molecule and induced a higher frequency of IFN-γ-expressing iNKT cells. Consequently, mice treated with DBM+αGC presented higher levels of serum IFN-γ than those treated with free agonist. Also, vectorized nanoparticles improved αGC ability to control the growth of murine...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research