Banks, M. A. | bioRxiv Science

bioRxiv2024

Nor-LAAM loaded PLGA Microparticles for Treating Opioid Use Disorder

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo--acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic-co-glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt.%) and an average diameter (19 {micro}m) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD.

bioengineering↗

bioRxiv2018

Anthropogenic habitat alteration leads to rapid loss of adaptive variation and restoration potential in wild salmon populations

Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism (i.e., phenotypic plasticity and/or genetic evolution) and potential to recover previous phenotypic characteristics are unclear. Here we investigate changes in adult migration characteristics of wild salmon populations caused by dam construction and other anthropogenic habitat modifications. Strikingly, we find that dramatic allele frequency change (i.e., genetic evolution) from strong selection at a single locus explains the rapid phenotypic shift observed after recent dam construction. Furthermore, ancient DNA analysis confirms the abundance of a specific allele associated with adult migration type in historical habitat that will soon become accessible through a large restoration (i.e., dam removal) project. However, analysis of contemporary samples suggests the restoration will be challenged by loss of the allele from potential source populations. These results highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.

genetics↗