Preparation and optimization of rivastigmine-loaded tocopherol succinate-based solid lipid nanoparticles

Rivastigmine hydrogen tartrate (RHT) is a pseudo-irreversible inhibitor of cholinesterase and is used for the treatment of Alzheimer's. However, RHT delivery to the brain is limited by the blood–brain barrier (BBB). The purpose of this study was to improve the brain-targeting delivery of RHT by producing and optimizing rivastigmine hydrogen tartrate-loaded tocopherol succinate-based solid lipid nanoparticles (RHT-SLNs). RHT-SLNs were prepared using the microemulsion technique. The impact of significant variables, such as surfactant concentration and drug/lipid ratio, on the size of RHT-SLNs and their drug loading and encapsulation efficiency was analysed using a five-level central composite design (CCD). The minimum size of particles and the maximum efficiency of loading and encapsulation were defined according to models derived from a statistical analysis performed under optimal predicted conditions. The experimental results of optimized RHT-SLNs showed an appropriate particle size of 15.6?nm, 72.4% drug encapsulation efficiency and 6.8% loading efficiency, which revealed a good correlation between the experimental and predicted values. Furthermore, in vitro release studies showed a sustained release of RHT from RHT-SLNs.     

Designing a new dimerized anti human TNF-α aptamer with blocking activity

The human tumor necrosis factor α (hTNF-α) is an important pro-inflammatory cytokine which plays critical roles in inflammatory diseases such as rheumatoid arthritis (RA). The anti-TNF-α proteins can reduce symptoms of RA. Due to limitations of protein-based therapies, it is necessary to find new anti-TNF-α agents instead of common anti-TNF-α proteins. Therefore, the aim of the current study was to identify a new DNA aptamer with anti-hTNF-α activity. The protein systematic evolution of ligands by exponential enrichment (SELEX) process was used for identifying DNA aptamers. Anti-hTNF-α aptamers were selected using dot blot, real-time PCR, and in vitro inhibitory assay. The selected aptamers were truncated in two steps, and finally, a dimer aptamer was constructed from different selected truncates to improve their inhibitory effect. Also, Etanercept was used as a positive control to inhibit TNF-α, in comparison to the designed aptamers. After 11 rounds, four aptamers with anti-hTNF-α inhibitory effect were identified. The truncation and dimerization strategy revealed a new dimer aptamer with 67 nM K_d, which has 40% inhibitory effect compared with Etanercept (60%). Overall, the dimerization and truncation aptamers could improve its activity. With regard to the several limitations of anti-TNF-α proteins therapies including immunogenicity, side effects, and cost-intensive, a new designed anti-hTNF-α dimer aptamer could be considered as a potential therapeutic and/or diagnostic agent for hTNF-α-related disorders.