Xu Nuo, Wixey Julie, Chand Kirat, Wong Megan, Nance Elizabeth
Department of Chemical Engineering, University of Washington, Seattle, WA, USA.
University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
Drug Deliv Transl Res. 2025 Mar 7. doi: 10.1007/s13346-025-01830-y.
Fetal growth restriction (FGR) affects 5% to 10% of all pregnancies in developed countries and is the second most leading cause of perinatal mortality and morbidity. Life-long consequences of FGR range from learning and behavioral issues to cerebral palsy. To support the newborn brain following FGR, timely and accessible neuroprotection strategies are needed. Curcumin-loaded polymeric nanoparticles, which have been widely explored for the treatment of cancer, neurological disorders, and bacterial infections, have the potential to prevent and mitigate pathogenic inflammatory processes in the FGR brain. Curcumin is a hydrophobic molecule with poor aqueous solubility and therefore has been incorporated into nanoparticles to improve solubility and delivery. However, curcumin loading in many nanoparticles can be limited to 10% by weight or lower. Here, we first optimize the formulation process of curcumin-loaded polymeric nanoparticles to find a tunable, reproducible, and stable formulation with high curcumin loading and encapsulation efficiency. We establish a curcumin formulation with 39% curcumin loading and > 95% curcumin encapsulation efficiency. Using this formulation, we assessed the biodistribution of polymeric nanoparticles in FGR piglets and normally grown (NG) piglets following different administration routes and evaluated brain cellular uptake. We show a significant amount of nanoparticle accumulation in the brain parenchyma of neonatal piglets as early as 4 h after intranasal administration. Nanoparticles colocalized in microglia, a therapeutic target of interest in FGR brain injury. This study demonstrates the potential of curcumin-loaded nanoparticles to treat neuroinflammation associated with FGR in the newborn.
胎儿生长受限（FGR）在发达国家影响着5%至10%的所有妊娠，是围产期死亡率和发病率的第二大主要原因。FGR的终身后果从学习和行为问题到脑瘫不等。为了在FGR后支持新生儿大脑，需要及时且可及的神经保护策略。负载姜黄素的聚合物纳米颗粒已被广泛用于治疗癌症、神经系统疾病和细菌感染，具有预防和减轻FGR大脑中致病性炎症过程的潜力。姜黄素是一种疏水分子，水溶性差，因此已被纳入纳米颗粒以提高溶解度和递送效果。然而，许多纳米颗粒中的姜黄素负载量可能限制在10%（重量）或更低。在此，我们首先优化负载姜黄素的聚合物纳米颗粒的配方工艺，以找到一种具有高姜黄素负载量和包封效率的可调谐、可重现且稳定的配方。我们建立了一种姜黄素负载量为39%且姜黄素包封效率大于95%的配方。使用该配方，我们评估了聚合物纳米颗粒在不同给药途径后在FGR仔猪和正常生长（NG）仔猪中的生物分布，并评估了大脑细胞摄取情况。我们发现，鼻内给药后仅4小时，新生仔猪脑实质中就有大量纳米颗粒积累。纳米颗粒与小胶质细胞共定位，小胶质细胞是FGR脑损伤中一个感兴趣的治疗靶点。这项研究证明了负载姜黄素的纳米颗粒治疗新生儿FGR相关神经炎症的潜力。
