title: Improving paclitaxel pharmacokinetics by using tumor-specific mesoporous silica nanoparticles with intraperitoneal delivery.
abstract: Mesoporous silica nanoparticles (MSNs) containing paclitaxel for intraperitoneal (i.p.) delivery were developed to exploit the tumor specific accumulation of these nanocarriers after i.p. injection and the slow release of paclitaxel from the MSNs. A 3.5-fold increase in tumor cellular drug uptake was observed for the paclitaxel-loaded MSNs compared with free paclitaxel. An in vivo study using xenograft mice bearing peritoneal human pancreatic carcinoma MIA PaCa-2 demonstrated that the MSN-paclitaxel formulation, compared to free paclitaxel, exhibited a 3.2-fold increase in peritoneal cavity residence time, slower absorption into the systemic circulation with one third systemic exposure, but a 6.5-fold increase in peritoneal tumor accumulation. Tissue distribution imaging showed significantly greater accumulation of fluorescent MSNs in tumor tissues compared to other peritoneal tissues. In conclusion, intraperitoneal administration of drug-containing MSNs was effective at reducing systemic exposure and increasing the peritoneal tumor accumulation of paclitaxel.
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA.
authors.forename: Derek
authors.initials: D
authors.lastname: Hargrove
authors.affiliation: Department of Pharmaceutical Sciences, University of Connecticut, Storrs, CT, 06269, USA. Electronic address: xiuling.lu@uconn.edu.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Lu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D053758:Nanoparticles; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000493:pharmacokinetics*; D016062:Porosity; D012822:Silicon Dioxide
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D012822:Silicon Dioxide; D017239:Paclitaxel
keywords: Intraperitoneal therapy; Mesoporous silica nanoparticles; Paclitaxel; Peritoneal cancer; Pharmacokinetics