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Use of a Piglet Model for the Study of Anesthetic-induced Developmental Neurotoxicity AIDN: A Translational Neuroscience Approach
Published on: June 11, 2017
Nano-formulated curcumin uptake and biodistribution in the fetal growth restricted newborn piglet brain
Nuo Xu1, Julie Wixey2, Kirat Chand2
1Department of Chemical Engineering, University of Washington, Seattle, WA, USA.
Insights
Curcumin nanoparticles effectively deliver therapeutic compounds to the newborn brain, offering a promising neuroprotection strategy for fetal growth restriction (FGR). This approach targets brain inflammation in FGR newborns, potentially mitigating long-term neurological issues.
Area of Science:
- Neuroscience
- Biomedical Engineering
- Pharmacology
Background:
- Fetal growth restriction (FGR) impacts 5-10% of pregnancies, leading to significant perinatal mortality and lifelong neurological deficits in newborns.
- Current neuroprotection strategies for FGR are limited, necessitating novel therapeutic approaches to support brain development.
- Curcumin, a potent anti-inflammatory agent, faces bioavailability challenges due to poor aqueous solubility, hindering its therapeutic application.
Purpose of the Study:
- To optimize curcumin-loaded polymeric nanoparticles for enhanced curcumin loading and encapsulation efficiency.
- To evaluate the brain biodistribution and cellular uptake of these nanoparticles in a preclinical model of FGR.
- To assess the potential of curcumin nanoparticles as a neuroprotective therapy for FGR-associated brain injury.
Main Methods:
- Optimized nanoparticle formulation to achieve high curcumin loading (39%) and encapsulation efficiency (>95%).
- Administered curcumin-loaded nanoparticles to fetal growth restriction (FGR) and normally grown (NG) piglets via different routes.
- Assessed nanoparticle biodistribution in the brain parenchyma and evaluated cellular uptake, specifically in microglia, using imaging techniques.
Main Results:
- Achieved a stable, reproducible curcumin nanoparticle formulation with high drug loading and encapsulation.
- Demonstrated significant accumulation of nanoparticles in the brain parenchyma of neonatal piglets within 4 hours of intranasal administration.
- Observed nanoparticle colocalization with microglia in the brain, indicating targeted delivery to a key cellular component involved in neuroinflammation.
Conclusions:
- Optimized curcumin-loaded polymeric nanoparticles offer a viable strategy for enhancing curcumin delivery to the brain.
- Intranasal administration facilitates rapid and efficient brain parenchymal accumulation of nanoparticles in neonates.
- Curcumin nanoparticles show potential for treating neuroinflammation and mitigating brain injury in newborns with FGR.
Abstract:
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.
