title: p-Aminophenyl-α-D-mannopyranoside engineered lipidic nanoparticles for effective delivery of docetaxel to brain.
abstract: Lipidic systems are considered to be the most promising carrier for drug delivery to brain. Metabolic substrates like carbohydrates and amino acids are able to traverse the blood-brain barrier (BBB) by specific carrier-mediated transport systems like glucose transporters present on the both luminal and abluminal side of the BBB. With this objective, the docetaxel (DTX) loaded solid lipidic nanoparticles were formulated and surface modified with a mannose derived ligand p-aminophenyl-α-D-mannopyranoside (MAN) to develop MAN conjugated lipidic nanoparticles for targeting DTX to brain. Lipidic nanoparticles were prepared using emulsification and solvent evaporation method using stearic acid as charge modifying lipid and conjugated with MAN using carbodimide coupling. These lipidic nanoparticles were successfully characterized using various techniques like DLS, TEM, DSC and FTIR spectroscopy. Cytotoxicity and cell uptake unveiled enhanced efficacy of conjugated lipidic nanoparticles. Pharmacokinetic and brain distribution studies demonstrated increased DTX concentrations using lipidic nanoparticles in brain and conjugating MAN on surface of lipidic nanoparticles further augmented the inflow of the drug to brain. Present study revealed the prospective of mannose analog, MAN-conjugated lipidic nanoparticles as efficient vehicle for anticancer drug delivery to brain.
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Indu
authors.initials: I
authors.lastname: Singh
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Swami
authors.affiliation: Department of Pharmacology, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Jeengar
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: wahid@niperhyd.ac.in.
authors.forename: Wahid
authors.initials: W
authors.lastname: Khan
authors.affiliation: Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India; Medicinal Chemistry and Pharmacology Division, Council of Scientific and Industrial Research-Indian Institute of Chemical Technology (CSIR-IICT), Hyderabad 500607, India. Electronic address: sistla@iict.res.in.
authors.forename: Ramakrishna
authors.initials: R
authors.lastname: Sistla
mesh_terms: D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008362:Mannosides / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D013329:Structure-Activity Relationship; D043823:Taxoids / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D014018:Tissue Distribution
chemical_list: D000814:Aniline Compounds; D000970:Antineoplastic Agents; D008055:Lipids; D008362:Mannosides; D043823:Taxoids; D000077143:Docetaxel; C034056:4-aminophenylmannoside
keywords: Blood–brain barrier; Conjugation; Docetaxel; Lipid; Solid lipid nanoparticle; Tumor; p-Aminophenyl-α-d-mannopyranoside