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

George R Dakwar; Elisa Zagato; Joris Delanghe; Sabrina Hobel; Achim Aigner; Hannelore Denys; Kevin Braeckmans; Wim Ceelen; Stefaan C De Smedt; Katrien Remaut

doi:10.1016/j.actbio.2014.03.012

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

Acta Biomater. 2014 Jul;10(7):2965-75. doi: 10.1016/j.actbio.2014.03.012. Epub 2014 Mar 19.

Authors

Affiliations

¹ Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium.
² Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium; Centre for Nano- and Biophotonics, Ghent University, Harelbekestraat 72, 9000 Ghent, Belgium.
³ Laboratory for Clinical Biology, Department of Clinical Chemistry, Microbiology and Immunology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
⁴ Rudolf Boehm Institute of Pharmacology and Toxicology, Clinical Pharmacology, University Leipzig, 04107 Leipzig, Germany.
⁵ Department of Medical Oncology, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
⁶ Department of Surgery, Ghent University Hospital, De Pintelaan 185, 9000 Ghent, Belgium.
⁷ Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium. Electronic address: stefaan.desmedt@ugent.be.
⁸ Laboratory for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent Research Group on Nanomedicines, Harelbekestraat 72, 9000 Ghent, Belgium. Electronic address: Katrien.Remaut@ugent.be.

PMID: 24657672
DOI: 10.1016/j.actbio.2014.03.012

Abstract

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.

Keywords: Aggregation; Drug delivery; Intraperitoneal administration; Peritoneal carcinomatosis; Release.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Ascitic Fluid / chemistry*
Colloids*
Drug Delivery Systems*
Infusions, Parenteral
Liposomes
Mice
Nanoparticles*

Substances

Colloids
Liposomes