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

Abstract

The 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 lung metastatic carcinoma. Thus, this is the first study showing that nano spray dryer technology is a simple and alternative approach to enhance iNKT responses.

• Authors: Michelangelo Bauwelz Gonzatti, Maria Eduarda Perrud Sousa, Ariane Simões Tunissi, Renato Arruda Mortara, Adriano Marim de Oliveira, Natália Neto Pereira Cerize, Alexandre de Castro Keller
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 565 Pg. 123-132 (Jun 30 2019) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 31075434 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Drug Carriers
• Galactosylceramides
• Methacrylates
• alpha-galactosylceramide

Topics

• Animals
• Cell Line
• Cytokines (immunology)
• Desiccation
• Drug Carriers (administration & dosage)
• Galactosylceramides (administration & dosage)
• Killer Cells, Natural (drug effects, immunology)
• Lung Neoplasms (drug therapy, secondary)
• Male
• Melanoma, Experimental (drug therapy, pathology)
• Methacrylates (administration & dosage)
• Mice, Inbred C57BL
• Nanoparticles (administration & dosage)
• Nanotechnology (methods)
• Natural Killer T-Cells (drug effects, immunology)