title: In vivo behavior and safety of lapatinib-incorporated lipid nanoparticles.
abstract: To improve the solubility, bioavailability and anti-tumor effect of lapatinib, lapatinib-incorporated lipid nanoparticles (LTNPs) were prepared and characterized. The particle size of LTNPs was 88.6 nm with a zeta potential of 20 mV. Laptinib was loaded into LTNPs with a non-crystal structure as determined by FT-IR. In vitro, LTNPs could be effectively uptaken into C6 glioma cells at a concentration-dependent manner. In vivo, LTNPs showed a relative higher AUC, which was 5.27- and 3.21-fold as that of Tykerb and lapatinib suspension (LTS) group. LTNPs also showed highest glioma concentration, which may benefit from the enhanced permeability and retention effect and active targeting ability. In toxicity studies, LTNPs displayed a half lethal dose over 250 mg/kg. Repeated administering 30 mg/kg of LTNPs could led to toxicity to hematology which might owe to the bovine serum albumin, a foreign protein to mice. However, there was no organic change observed through HE staining. In conclusion, LTNPs could target to glioma with high concentration and low side effect.
authors.forename: Huile
authors.initials: H
authors.lastname: Gao
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.forename: Zhangjie
authors.initials: Z
authors.lastname: Xi
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Shilei
authors.initials: S
authors.lastname: Cao
authors.affiliation: School of Pharmacy, Fudan University, Key Laboratory of Smart Drug Delivery (Fudan University), Ministry of Education, 826 Zhangheng Road, Shanghai, 201203, China. xgjiang@shmu.edu.cn.
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry*; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D007275:Injections, Intravenous; D000077341:Lapatinib; D007928:Lethal Dose 50; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008813:Mice, Inbred ICR; D053758:Nanoparticles / Q000737:chemistry*; D009928:Organ Specificity; D010316:Particle Size; D011799:Quinazolines / Q000493:pharmacokinetics / Q000627:therapeutic use / Q000633:toxicity; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D013607:Tablets; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D008055:Lipids; D011799:Quinazolines; D013607:Tablets; D000077341:Lapatinib