title: Ligand anchored poly(propyleneimine) dendrimers for brain targeting: Comparative in vitro and in vivo assessment.
abstract: The present investigation was aimed at developing various ligands-anchored dendrimers and comparing their brain targeting potential at one platform. Sialic acid (S), glucosamine (G) and concanavalin A (C) anchored poly(propyleneimine) (PPI) dendritic nanoconjugates were developed and evaluated for delivery of anti-cancer drug, paclitaxel (PTX) to the brain. MTT assay on U373MG human astrocytoma cells indicated IC50 values of 0.40, 0.65, 0.95, 2.00 and 3.50μM for PTX loaded SPPI, GPPI, CPPI, PPI formulations, and free PTX, respectively. The invivo pharmacokinetics and biodistribution studies in rats showed significantly higher accumulation of PTX in brain as compared to free PTX. The order of targeting potential of various ligands under investigation was found as sialic acid>glucosamine>concanavalin A. Thus, it can be concluded that sialic acid, glucosamine and Con A can be used as potential ligands to append PPI dendrimers for enhanced delivery of anticancer drugs to the brain for higher therapeutic outcome.
authors: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470 003, India.
authors: Hemant K
authors: HK
authors: Patel
authors: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470 003, India; Center for Nanobioscience, Agharkar Research Institute, Pune 411004, India. Electronic address: cme_virendra@yahoo.co.in.
authors: Virendra
authors: V
authors: Gajbhiye
authors: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470 003, India; Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA. Electronic address: prashantdops@gmail.com.
authors: Prashant
authors: P
authors: Kesharwani
authors: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar 470 003, India. Electronic address: jnarendr@yahoo.co.in.
authors: Narendra K
authors: NK
authors: Jain
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003208:Concanavalin A / Q000737:chemistry; D050091:Dendrimers / Q000737:chemistry* / Q000493:pharmacokinetics; D004339:Drug Compounding; D065546:Drug Liberation; D005944:Glucosamine / Q000737:chemistry; D006801:Humans; D007275:Injections, Intravenous; D008024:Ligands; D058990:Molecular Targeted Therapy; D058726:Nanoconjugates / Q000737:chemistry* / Q000627:therapeutic use / Q000648:ultrastructure; D017239:Paclitaxel / Q000493:pharmacokinetics* / Q000494:pharmacology; D011126:Polypropylenes / Q000737:chemistry*; D051381:Rats; D012794:Sialic Acids / Q000737:chemistry; D014018:Tissue Distribution
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050091:Dendrimers; D008024:Ligands; D058726:Nanoconjugates; D011126:Polypropylenes; D012794:Sialic Acids; C443641:poly(propyleneimine); D003208:Concanavalin A; D005944:Glucosamine; D017239:Paclitaxel
keywords: Brain tumor; Dendrimer; Drug delivery; Paclitaxel; Targeting