Next-generation poly-L-histidine formulations for miRNA mimic delivery.

Many diseases, especially cancer, are caused by the abnormal expression of non-coding microRNAs (miRNAs), which regulate gene expression, leading to the development of miRNA-based therapeutics. Synthetic miRNA inhibitors have shown promising efficacy in blocking the activity of aberrant miRNAs that are upregulated in disease-specific pathologies. On the other hand, miRNAs that aid in preventing certain diseases and are reduced in expression in the disease state need different strategies. To tackle this, miRNA mimics, which mimic the activity of endogenous miRNAs, can be delivered for those miRNAs downregulated in different disease states. However, the delivery of miRNA mimics remains a challenge. Here, we report a cationic polylactic-co-glycolic acid (PLGA)-poly-L-histidine delivery system to deliver miRNA mimics. We chose miR-34a mimics as a proof of concept for miRNA delivery. miR-34a-loaded PLGA-poly-L-histidine nanoparticles (NPs) were formulated and biophysically characterized to analyze the structural properties of miRNA mimic-loaded NPs. In vitro efficacy was determined by investigating miR-34a and downstream target levels and performing cell viability and apoptosis assays. We confirmed in vivo efficacy through prolonged survival of miR-34a NP-treated A549-derived xenograft mice treated intratumorally. The results of these studies establish PLGA-poly-L-histidine NPs as an effective delivery system for miRNA mimics for treating diseases characterized by downregulated miRNAs.

Nanoparticle delivery systems for substance use disorder.

Innovative breakthroughs in nanotechnology are having a substantial impact in healthcare, especially for brain diseases where effective therapeutic delivery systems are desperately needed. Nanoparticle delivery systems offer an unmatched ability of not only conveying a diverse array of diagnostic and therapeutic agents across complex biological barriers, but also possess the ability to transport payloads to targeted cell types over a sustained period. In substance use disorder (SUD), many therapeutic targets have been identified in preclinical studies, yet few of these findings have been translated to effective clinical treatments. The lack of success is, in part, due to the significant challenge of delivering novel therapies to the brain and specific brain cells. In this review, we evaluate the potential approaches and limitations of nanotherapeutic brain delivery systems. We also highlight the examples of promising strategies and future directions of nanocarrier-based treatments for SUD.