β-Hydroxybutyric acid grafted solid lipid nanoparticles: A novel strategy to improve drug delivery to brain

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 EditorThe 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.

Graphical AbstractDrug delivery across the blood brain barrier is an elusive target in the treatment of neurological diseases. To resolve this problem, beta-hydroxybutyric acid (HBA) conjugated docetaxel loaded solid lipid nanoparticles (HD-SLNs) were prepared and characterized for its particle size, zeta potential, in vitro release, cytotoxicity and cellular uptake studies. Surface modification of SLNs was confirmed with X-ray photon spectroscopy. These nanoparticles were transported across the BBB using both passive and carrier mediated transporter using MCT1 transporter. Hence, cell uptake studies revealed the increased uptake of docetaxel with HD-SLNs. Pharmacokinetic and brain distribution studies in rats revealed the increased brain uptake of docetaxel with HD-SLNs.Figure optionsDownload high-quality image (188 K)Download as PowerPoint slide