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Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice.

ABSTRACT: Neuropathic pain is a disease caused by structural and functional plasticity in central and peripheral sensory pathways that produce alterations in nociceptive processing. Currently, pharmacological treatment for this condition remains a challenge. Crotoxin (CTX), the main neurotoxin of Crotalus durissus terrificus rattlesnake venom, has well described prolonged anti-inflammatory and antinociceptive activities. In spite of its potential benefits, the toxicity of CTX remains a limiting factor for its use. SBA-15 is an inert nanostructured mesoporous silica that, when used as a vehicle, may reduce toxicity and potentiate the activity of different compounds. Based on this, we propose to conjugate crotoxin with SBA-15 (CTX:SBA-15) in order to investigate if when adsorbed to silica, CTX would have its toxicity reduced and its analgesic effect enhanced in neuropathic pain induced by the partial sciatic nerve ligation (PSNL) model. SBA-15 enabled an increase of 35% of CTX dosage. Treatment with CTX:SBA-15 induced a long-lasting reduction of mechanical hypernociception, without modifying the previously known pathways involved in antinociception. Moreover, CTX:SBA-15 reduced IL-6 and increased IL-10 levels in the spinal cord. Surprisingly, the antinociceptive effect of CTX:SBA-15 was also observed after oral administration. These data indicate the potential use of the CTX:SBA-15 complex for neuropathic pain control and corroborates the protective potential of SBA-15.

SUBMITTER: Sant'Anna MB

PROVIDER: S-EPMC6949982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Various cosmetics having a single function are increasingly being used, but cosmetics having multifunctional activities remain limited. We aimed to develop a multifunctional cosmetic cream having antioxidant, anti-tyrosinase, anti-aging and antimicrobial activities. Antimicrobial activities were performed by disc-diffusion method. Cell toxicity and cell proliferations were evaluated in a 96-well plate with different cell lines such as HaCaT, RAW264.7, CCD-986Sk, B16F1, and B16F10. Mushroom tyrosinase inhibition, elastase inhibition, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities were evaluated and IC50 was calculated. Mesoporous silica particle was synthesized using Pluronic P123 and tetraethyl ortho-silicate (TEOS). Facial pictures were captured by VISIA-CR (Facial Imaging System for Clinical Research). Roughness of image was analysed by PRIMOS software and brightness of image was analyzed by Chromameter CR-400. The crude product of strain T65 inhibited the different human pathogenic bacteria such as Bacillus subtilis, Escherichia coli, Propionibacterium acnes, Staphylococcus aureus, Pseudomonas aeruginosa, and Staphylococcus epidermidis. The IC50 of T65 crude product for mushroom tyrosinase, elastase, and DPPH radical scavenging activities were 58.73, 14.68, and 6.31 µg/mL, respectively. T65 crude product proliferated collagen type I in CCD-986Sk cell up to 145.91% ± 9.11% (mean ± SD; mean of 24, 48, and 72 h) at 250 pg/mL. Synthesized mesoporous particles (SBA-15) confirmed the sustainable performance by control-release for three days. Formulated functional cosmetic cream containing T65 embedded SBA-15, significantly decreased the skin roughness by 4.670% and increased the skin brightness by 0.472% after application of 4 weeks. T65 crude product inhibited both Gram-positive and Gram-negative pathogens. Synthesized mesoporous particle, SBA-15, confirmed the physiologically active substance was released in sustainable release condition. T65 crude product showed impeccable antimicrobial, antioxidant, anti-aging, and whitening activities with non-cytotoxic effects to different cell lines related to the human skin.

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Crotoxin Conjugated to SBA-15 Nanostructured Mesoporous Silica Induces Long-Last Analgesic Effect in the Neuropathic Pain Model in Mice.

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