Biocompatible nanoparticles intercalated with anticancer drug for target delivery: pharmacokinetic and biodistribution study.
We have developed new hybrid systems consisting of anticancer drugs such as methotrexate (MTX) or 5-fluorouracil (5-FU) and two-dimensional inorganic delivery carrier like layered double hydroxide (LDH). Such an inorganic vector with biocompatible metal ions can be used to overcome toxicity, immunogenecity and poor integration capacity, which are critical problems caused by conventional viral vectors, cationic liposomes and polymers. Moreover, the intercellular mechanism of LDH nanoparticles is primarily related to clathrin-mediated endocytosis, resultihg in effective delivery and eventually enhancing drug efficacy. In this report, the effect of LDH intercalated with 5-Fu (5-Fu-LDH) was evaluated in whole animal by studying pharmacokinetic behavior and tissue distribution. The results showed that 5-Fu-LDH exhibited favorable blood clearance profiles compared to free 5-Fu, such as sustained drug release, prolonged drug half-life, and increased drug accumulation in target tumor tissue. Furthermore, LDH nanoparticles were rapidly excreted from the body and not accumulated in the organs after administration as 5-Fu-LDH. Therefore, the hybrid system can be promising anticancer chemotherapy agent for tumor targeting with biocompatibility.
Choi
Soo-Jin
SJ
Center for Intelligent Nano-Bio Materials, Division of Nano Sciences BK21, Department of Bioinspired Science and Department of Chemistry and Nano Science, Ewha Womans University, Seoul, 120-750, Korea.
Oh
Jae-Min
JM
Choy
Jin-Ho
JH
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003460:Crystallization / Q000379:methods; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D008422:Materials Testing; D008657:Metabolic Clearance Rate; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D050997:Nanomedicine / Q000379:methods*; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009928:Organ Specificity; D012516:Osteosarcoma / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010316:Particle Size; D013499:Surface Properties; D014018:Tissue Distribution; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D004337:Drug Carriers; D005472:Fluorouracil