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Heterotopic Mucosal Engrafting Procedure for Direct Drug Delivery to the Brain in Mice
Published on: July 16, 2014
β-Hydroxybutyric acid grafted solid lipid nanoparticles: a novel strategy to improve drug delivery to brain
Vinay Kumar Venishetty1, Ramakrishna Samala, Rojarani Komuravelli
1Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Andhra Pradesh, India. vvk282@gmail.com
Abstract:
Delivery of drugs to brain is an elusive task in the therapy of many serious neurological diseases. With the aim to create a novel formulation to enhance the drug uptake to brain, betreliesoxybutyric acid (HBA) grafted docetaxel loaded solid lipid nanoparticles (HD-SLNs) were explored. Transportation of HD-SLNs relies on the transport of novel ligand, HBA, by monocarboxylic acid transporter (MCT1). Expression of MCT1 transporter on brain endothelial cells (bEnd cells) was studied using immunocytochemistry. Stearylamine-HBA conjugate was used to modify the surface of SLNs and it was confirmed using XPS (X-Ray Photon Spectroscopy) analysis. In vitro release studies revealed the controlled release of drug from HD-SLNs. Cytotoxicity and cell uptake studies revealed the increased uptake of docetaxel with HD-SLNs. Mechanism involved in the uptake of HD-SLNs was studied in bEnd cells by saturating MCT1 with excess HBA. Pharmacokinetic and brain distribution demonstrated increased docetaxel concentrations in brain compared with Taxotere®.
From The Clinical Editor:
The authors of this study demonstrate enhanced drug delivery to the brain using a novel formulation of beta-hydroxybutyric acid grafted docetaxel loaded solid lipid nanoparticles. The results show increased uptake of docetaxel compared with Taxotere.
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