“…However, to the best of our knowledge, no other study has reported codelivery of these two therapeutics, probably due to their different physical and chemical properties making coencapsulation challenging. BDNF, for example, is a hydrophilic protein with a molecular mass of 14 kDa, 39 while DEX is a small hydrophobic molecule with a molecular mass of 392 Da. 40 The ability of MSG-SPs to coencapsulate and simultaneously release these drugs, therefore, highlights their potential for the treatment of sensorineural hearing loss.…”
This paper reports a facile and robust mold-templated technique for the assembly of mesoporous silica (MS) supraparticles and demonstrates their potential as vehicles for codelivery of brain-derived neurotrophic factor (BDNF) and dexamethasone (DEX). The MS supraparticles are assembled using gelatin as a biodegradable adhesive to bind and cross-link the particles. Microfabricated molds made of polydimethylsiloxane are used to control the size and shape of the supraparticles. The obtained mesoporous silica-gelatin hybrid supraparticles (MSG-SPs) are stable in water as well as in organic solvents, such as dimethyl sulfoxide, and efficiently coencapsulate both BDNF and DEX. The MSG-SPs also exhibit sustained release kinetics in simulated physiological conditions (>30 days), making them potential candidates for long-term delivery of therapeutics to the inner ear.
“…However, to the best of our knowledge, no other study has reported codelivery of these two therapeutics, probably due to their different physical and chemical properties making coencapsulation challenging. BDNF, for example, is a hydrophilic protein with a molecular mass of 14 kDa, 39 while DEX is a small hydrophobic molecule with a molecular mass of 392 Da. 40 The ability of MSG-SPs to coencapsulate and simultaneously release these drugs, therefore, highlights their potential for the treatment of sensorineural hearing loss.…”
This paper reports a facile and robust mold-templated technique for the assembly of mesoporous silica (MS) supraparticles and demonstrates their potential as vehicles for codelivery of brain-derived neurotrophic factor (BDNF) and dexamethasone (DEX). The MS supraparticles are assembled using gelatin as a biodegradable adhesive to bind and cross-link the particles. Microfabricated molds made of polydimethylsiloxane are used to control the size and shape of the supraparticles. The obtained mesoporous silica-gelatin hybrid supraparticles (MSG-SPs) are stable in water as well as in organic solvents, such as dimethyl sulfoxide, and efficiently coencapsulate both BDNF and DEX. The MSG-SPs also exhibit sustained release kinetics in simulated physiological conditions (>30 days), making them potential candidates for long-term delivery of therapeutics to the inner ear.
“… 60 In this state, pro-BDNF/p75 NTR through activation of caspase 3 may lead to neuronal injury, apoptosis, and induction of epileptogenesis. 61 Therefore, direct inhibition of the pro-BDNF/p75 NTR signaling pathway or indirect suppression of caspase 3 could be an effective therapeutic strategy in epilepsy ( Figure 4 ). Figure 4.…”
Section: Mechanistic Pathways Of P75
Ntr
In Epilepsymentioning
Epilepsy is a chronic neurological disorder manifested by recurring unprovoked seizures resulting from an imbalance in the inhibitory and excitatory neurotransmitters in the brain. The process of epileptogenesis involves a complex interplay between the reduction of inhibitory gamma-aminobutyric acid (GABA) and the enhancement of excitatory glutamate. Pro-BDNF/p75NTR expression is augmented in both glial cells and neurons following epileptic seizures and status epileptics (SE). Over-expression of p75NTR is linked with the pathogenesis of epilepsy, and augmentation of pro-BDNF/p75NTR is implicated in the pathogenesis of epilepsy. However, the precise mechanistic function of p75NTR in epilepsy has not been completely elucidated. Therefore, this review aimed to revise the mechanistic pathway of p75NTR in epilepsy.
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