Application of microneedle arrays for enhancement of transdermal permeation of Insulin: in vitro experiments, scaling analyses and numerical simulations

The aim of this investigation is to study the effect of donor concentration and microneedle (MN) length on permeation of insulin and further evaluating the data using scaling analyses and numerical simulations. Histological evaluation of skin sections was carried to evaluate the skin disruption and depth of penetration by MNs. Scaling analyses was done using dimensionless parameters like concentration of drug (Ct/Cs), thickness (h/L) and surface area of the skin (Sa/L2). Simulation studies were carried out using MATLAB and COMSOL software to simulate the insulin permeation using histological sections of MN treated skin and experimental parameters like passive diffusion coefficient. A 1.6 fold increase in transdermal flux and 1.9 fold decrease in lag time values were observed with 1.5mm MN when compared with passive studies. Good correlation (R2>0.99) was observed between different parameters using scaling analyses. Also, the in vitro and simulated permeations profiles were found to be similar (f2≥50). Insulin permeation significantly increased with increase in donor concentration and MN length (p<0.05). The developed scaling correlations and numerical simulations were found to be accurate and would help researchers to predict the permeation of insulin with new dimensions of MN in optimizing insulin delivery. Overall, it can be inferred that the application of MNs can significantly enhance insulin permeation and may be an efficient alternative for injectable insulin therapy in humans

Targeting Aggrephagy for the Treatment of Alzheimer’s Disease

Alzheimer&rsquo;s disease (AD) is one of the most common neurodegenerative diseases in older individuals with specific neuropsychiatric symptoms. It is a proteinopathy, pathologically characterized by the presence of misfolded protein (A&beta; and Tau) aggregates in the brain, causing progressive dementia. Increasing studies have provided evidence that the defect in protein-degrading systems, especially the autophagy-lysosome pathway (ALP), plays an important role in the pathogenesis of AD. Recent studies have demonstrated that AD-associated protein aggregates can be selectively recognized by some receptors and then be degraded by ALP, a process termed aggrephagy. In this study, we reviewed the role of aggrephagy in AD development and discussed the strategy of promoting aggrephagy using small molecules for the treatment of AD