Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice
Abstract
:1. Introduction
2. Results
2.1. CTX LD50 Increased When Adsorbed to SBA-15
2.2. CTX:SBA-15 Prolongs the Antinociceptive Effect of CTX in the PSNL Model
2.3. CTX:SBA-15 Complex Does Not Alter CTX Analgesic Mechanisms of Action Related to the Involvement of Formyl Peptide, α2-Adrenergic and Muscarinic Receptors
2.4. CTX Orally Administered Only Presents Analgesic Activity When Adsorbed to SBA-15
2.5. Both CTX and CTX:SBA-15 Treatments Reduce Iba-1 and GFAP Spinal Cord Expression Induced by PSNL
2.6. Both CTX and CTX:SBA-15 Modulate the Production and Release of Cytokines Induced by PSNL Model
2.7. Antibodies Produced after CTX:SBA-15 Immunization Protect Against CTX Lethality and Do Not Affect CTX or CTX:SBA-15 Analgesic Effect
3. Discussion
4. Conclusions
5. Materials and Methods
5.1. Animals
5.2. Crotoxin (CTX)
5.3. SBA-15 Synthesis
5.4. Preparation of the Complex (CTX:SBA-15)
5.5. Drug Administration
5.6. Lethal Dose (LD50) Determination
5.7. General Experimental Design
5.8. Neuropathic Pain Model—Partial Sciatic Nerve Ligation (PSNL)
5.9. Behavioural Test—Mechanical Hypernociception Assessment Using von Frey Filaments
5.10. Glia Cell Expression Evaluated by Western Blotting
5.11. Cytokine Level Evaluation
5.12. Anti-CTX Antibody Titration by ELISA and Passive Immunization
5.13. Data Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
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Titration of Antibodies | ||
---|---|---|
Groups | 15 days after first dose | 20 days after second dose |
Naive | 256 | 256 |
SBA-15 | 256 | 128 |
CTX | 256 | 1024 |
CTX:SBA-15 | 256 | 4096 |
CTX:Al(OH)3 | 256 | 32,768 |
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Sant’Anna, M.B.; Lopes, F.S.R.; Kimura, L.F.; Giardini, A.C.; Sant’Anna, O.A.; Picolo, G. Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice. Toxins 2019, 11, 679. https://doi.org/10.3390/toxins11120679
Sant’Anna MB, Lopes FSR, Kimura LF, Giardini AC, Sant’Anna OA, Picolo G. Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice. Toxins. 2019; 11(12):679. https://doi.org/10.3390/toxins11120679
Chicago/Turabian StyleSant’Anna, Morena Brazil, Flavia Souza Ribeiro Lopes, Louise Faggionato Kimura, Aline Carolina Giardini, Osvaldo Augusto Sant’Anna, and Gisele Picolo. 2019. "Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice" Toxins 11, no. 12: 679. https://doi.org/10.3390/toxins11120679