title: Stability, Pharmacokinetics, Biodistribution and Safety Assessment of Folate-Conjugated Pullulan Acetate Nanoparticles as Cervical Cancer Targeted Drug Carriers.
abstract: It is recognized that the stability and journey in the body of nanoparticles are important issues for drug formulations. In this study, we prepared folate-conjugated pullulan acetate nanoparticles (FPANs) and epirubicin loaded FPANs (FPA/EPI) using dialysis method. The storage stability of FPANs and FPA/EPI at 4 degrees C could be up to 3 months. Using folate receptor overexpressed Hela cells, dose dependent cellular uptake and receptor-mediated endocytosis of FPA/EPI were confirmed. From the in vivo pharmacokinetics test, compared to free EPI, half-life time (t½) of FPA/EPI was extended 1.57 times and the area under-the-curve (AUC) increased 3.95 times as well. In addition, biodistribution data showed that, EPI concentration in tumor in FPA/EPI group was 2.01 times higher than that in free EPI group after 96 h; The concentration of drug in liver treated by FPA/EPI was 5.7-11.6 times, while in heart, kidney, especially in stomach and intestine were much lower than those in free EPI group from 24 to 96 h. Furthermore, blank FPANs showed no apparent acute toxicity at dose up to 125 mg/kg. All results suggested that FPA/EPI showed a promising potential on treating cervical carcinoma and its metastatic hepatocellular carcinoma in future because of the high stability, less toxicity and tumor targeting.
authors.forename: Hongbo
authors.initials: H
authors.lastname: Tang
authors.forename: Xin
authors.initials: X
authors.lastname: Feng
authors.forename: Tong
authors.initials: T
authors.lastname: Zhang
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Dai
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Zhou
authors.forename: Hongli
authors.initials: H
authors.lastname: Chen
authors.forename: Lingrong
authors.initials: L
authors.lastname: Liu
authors.forename: Xuemin
authors.initials: X
authors.lastname: Li
authors.forename: Taifeng
authors.initials: T
authors.lastname: Zhuang
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.forename: Qiqing
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics / Q000633:toxicity*; D004355:Drug Stability; D015251:Epirubicin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D005260:Female; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D005936:Glucans / Q000737:chemistry / Q000633:toxicity*; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008819:Mice, Nude; D053758:Nanoparticles / Q000737:chemistry / Q000633:toxicity*; D017208:Rats, Wistar; D014018:Tissue Distribution; D002583:Uterine Cervical Neoplasms
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D005936:Glucans; D015251:Epirubicin; C009109:pullulan; D005492:Folic Acid