| Full text | |
| Author(s): |
Gonzatti, Michelangelo Bauwelz
[1, 2, 3, 4]
;
Perrud Sousa, Maria Eduarda
[1, 2]
;
Tunissi, Ariane Simoes
[3, 4]
;
Mortara, Renato Arruda
[1, 2]
;
de Oliveira, Adriano Marim
[3, 4]
;
Pereira Cerize, Natalia Neto
[3, 4]
;
Keller, Alexandre de Castro
[1]
Total Authors: 7
|
| Affiliation: | [1] Univ Fed Sao Paulo, Dept Microbiol Immunol & Parasitol, Escola Paulista Med, Sao Paulo - Brazil
[2] Escola Paulista Med, Disciplina Imunol, Rua Botucatu 862, 4 Andar, BR-05023062 Sao Paulo, SP - Brazil
[3] Inst Technol Res State Sao Paulo, Sao Paulo - Brazil
[4] Inst Pesquisas Tecnol Estado Sao Paulo SA, Av Prof Almeida Prado 532, Cidade Univ, BR-05508901 Sao Paulo, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | International Journal of Pharmaceutics; v. 565, p. 123-132, JUN 30 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
The recognition of a-galactosylceramide (alpha GC), 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 alpha GC 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 alpha GC 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 alpha GC-vectorized nanoparticles (DBM + alpha GC) with a more potent biological activity than the free agonist. DBM nanoparticles improved in vivo alpha GC loading into the CD1d molecule and induced a higher frequency of IFN-gamma-expressing iNKT cells. Consequently, mice treated with DBM + alpha GC presented higher levels of serum IFN-gamma than those treated with free agonist. Also, vectorized nanoparticles improved alpha GC 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. (AU) | |
| FAPESP's process: | 16/02189-1 - Incorporation of glycosphingolipids into nanoparticles to immunotherapy using invariant Natural Killer T lymphocytes |
| Grantee: | Alexandre de Castro Keller |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 17/12799-4 - Glycolipids incorporation to coloidal polimeric nanocarriers as alternative iNKT lymphocyte based immunotherapy |
| Grantee: | Michelangelo Bauwelz Gonzatti |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 16/15000-4 - Trypanosoma cruzi: intra and interspecific genomic variability and mechanisms of cell invasion/egress |
| Grantee: | Renato Arruda Mortara |
| Support Opportunities: | Research Projects - Thematic Grants |