title: β-Hydroxybutyric acid grafted solid lipid nanoparticles: a novel strategy to improve drug delivery to brain.
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®.
  
  
  BACKGROUND
  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.
authors.affiliation: Pharmacology Division, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, Andhra Pradesh, India. vvk282@gmail.com
authors.forename: Vinay Kumar
authors.initials: VK
authors.lastname: Venishetty
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Samala
authors.forename: Rojarani
authors.initials: R
authors.lastname: Komuravelli
authors.forename: Madhusudana
authors.initials: M
authors.lastname: Kuncha
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
authors.forename: Prakash V
authors.initials: PV
authors.lastname: Diwan
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D000077143:Docetaxel; D016503:Drug Delivery Systems; D004355:Drug Stability; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D056951:Photoelectron Spectroscopy; D011208:Powders; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D027981:Symporters / Q000378:metabolism; D043823:Taxoids / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D014961:X-Ray Diffraction; D000099233:Monocarboxylate Transport Protein 1
chemical_list: D020155:3-Hydroxybutyric Acid; D000588:Amines; D000077143:Docetaxel; D008055:Lipids; D027501:Monocarboxylic Acid Transporters; D011208:Powders; D027981:Symporters; D043823:Taxoids; D000099233:Monocarboxylate Transport Protein 1; C009317:stearylamine