Colloidal stability of nano-sized particles in the peritoneal fluid: Towards optimizing drug delivery systems for intraperitoneal therapy

被引：62

作者：

Dakwar, George R. ^{[1
]}

Zagato, Elisa ^{[1
,5
]}

Delanghe, Joris ^{[2
]}

Hobel, Sabrina ^{[3
]}

Aigner, Achim ^{[3
]}

Denys, Hannelore ^{[4
]}

Braeckmans, Kevin ^{[1
,5
]}

Ceelen, Wim ^{[6
]}

De Smedt, Stefaan C. ^{[1
]}

Remaut, Katrien ^{[1
]}

机构：

[1] Univ Ghent, Fac Pharm, Lab Gen Biochem & Phys Pharm, Ghent Res Grp Nanomed, Harelbekestr 72, B-9000 Ghent, Belgium

[2] Ghent Univ Hosp, Dept Clin Chem Microbiol & Immunol, Lab Clin Biol, B-9000 Ghent, Belgium

[3] Univ Leipzig, Rudolf Boehm Inst Pharmacol & Toxicol Clin Pharma, D-04107 Leipzig, Germany

[4] Ghent Univ Hosp, Dept Med Oncol, B-9000 Ghent, Belgium

[5] Univ Ghent, Ctr Nano & Biophoton, B-9000 Ghent, Belgium

[6] Ghent Univ Hosp, Dept Surg, B-9000 Ghent, Belgium

来源：

ACTA BIOMATERIALIA | 2014年 / 10卷 / 07期

基金：

比利时弗兰德研究基金会;

关键词：

Drug delivery; Aggregation; Peritoneal carcinomatosis; Intraperitoneal administration; Release; FLUORESCENCE CORRELATION SPECTROSCOPY; METASTATIC COLORECTAL-CANCER; III OVARIAN-CANCER; PHASE-III; PLUS OXALIPLATIN; BLOOD COMPONENTS; HUMAN SERUM; NANOPARTICLES; PACLITAXEL; LIPOSOMES;

D O I：

10.1016/j.actbio.2014.03.012

中图分类号：

R318 [生物医学工程];

学科分类号：

100103 [病原生物学];

摘要：

Intraperitoneal (IP) administration of nano-sized delivery vehicles containing small interfering RNA (siRNA) has recently gained attention as an alternative route for the efficient treatment of peritoneal carcinomatosis. The colloidal stability of nanomatter following IP administration has, however, not been thoroughly investigated yet. Here, enabled by advanced microscopy methods such as single particle tracking and fluorescence correlation spectroscopy, we follow the aggregation and cargo release of nano-scaled systems directly in peritoneal fluids from healthy mice and ascites fluid from a patient diagnosed with peritoneal carcinomatosis. The colloidal stability in the peritoneal fluids was systematically studied as a function of the charge (positive or negative) and poly(ethylene glycol) (PEG) degree of liposomes and polystyrene nanoparticles, and compared to human serum. Our data demonstrate strong aggregation of cationic and anionic nanoparticles in the peritoneal fluids, while only slight aggregation was observed for the PEGylated ones. PEGylated liposomes, however, lead to a fast and premature release of siRNA cargo in the peritoneal fluids. Based on our observations, we reflect on how to tailor improved delivery systems for IP therapy. (C) 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

引用

页码：2965 / 2975

页数：11

共 59 条

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Intraperitoneal cisplatin plus intravenous cyclophosphamide versus intravenous cisplatin plus intravenous cyclophosphamide for stage III ovarian cancer [J].