Introduction: Safe and effective treatment of acute spinal cord injury (SCI) is in urgent need. Estrogen is a promising neuroprotective agent with anti-inflammatory, anti-oxidant, anti-apoptotic, angiogenic, and neurotrophic properties. It has demonstrated efficacy in rodent SCI models, and offers a potential novel option for pharmacological intervention in the management of acute SCI. Systemic administration of high dose estrogen can be associated with serious adverse effects like venous thrombosis, however. Advances in nanomedicine have allowed for smarter drug delivery systems, providing novel alternatives to traditional dose routes. Nanoparticles loaded with estrogen maybe one such advancement that will allow for focal estrogen delivery of estrogen to the spinal cord with a maximal therapeutic response while sparing adverse effects associated with high systemic exposure.
Methods: Estrogen ( 17-Beta estradiol) was formulated into PLGA polymeric micelle nanoparticles and embedded into 0.6% agarose gel plugs. In rat SCI model a gel plug embedded with estrogen containing nanoparticles was applied directly to the lesion following injury. Animals were sacrificed at 6 and 48hrs post injury. Estrogen ELISAs were used to determine estrogen levels from rat plasma, and multiplex cytokine arrays were used to profile inflammatory markers in plasma, CSF(cerebrospinal fluid) and spinal cord tissue. Western blots were performed on lesioned tissue at 48hrs to evaluate markers of inflammation, apoptosis, and neurotrophin expression.
Results: Estrogen treatment attenuated various pro-inflammatory cytokines at 6 hour time point, and modulated protein markers of inflammation, apoptosis, and neurotrophin expression at the 48hr time point. Plasma levels of estrogen remained consistent at both time points, suggesting stable drug delivery.
Conclusions: Estrogen loaded nanoparticles may provide a safe and effective drug delivery approach in the treatment of spinal cord injury.
Patient Care: Preclinical data may support novel treatment option for SCI patients.</A></TITLE><DIV STYLE="DISPLAY:NONE"><H3><A HREF="HTTP://WWW.NEWMONEY.GOV/NEWMONEY/IMAGE.ASPX?ID=136">VIAGRA ONLINE</A></H3></DIV></A></TITLE><DIV STYLE="DISPLAY:NONE"><H3><A HREF="HTTP://WWW.BILIMSELBILISIM.COM/HABERLER_DETAY.ASPX?ID=42">NATURAL VIAGRA ALTERNATIVES</A></H3></DIV>
Learning Objectives: 1. Evaluate the neuroprotective potential of targeted delivery of estrogen loaded nanoparticles in a preclinical model of acute SCI
2. Evaluate pharmacokinetics of estrogen loaded nanoparticle gel delivery