The Pharmacokinetics and Biodistribution of a 64 kDa PolyPEG Star Polymer After Subcutaneous and Pulmonary Administration to Rats

Song Yang Khor; Jinming Hu; Victoria M McLeod; John F Quinn; Christopher J H Porter; Michael R Whittaker; Lisa M Kaminskas; Thomas P Davis

doi:10.1016/j.xphs.2015.11.038

The Pharmacokinetics and Biodistribution of a 64 kDa PolyPEG Star Polymer After Subcutaneous and Pulmonary Administration to Rats

J Pharm Sci. 2016 Jan;105(1):293-300. doi: 10.1016/j.xphs.2015.11.038. Epub 2016 Jan 13.

Authors

Song Yang Khor¹, Jinming Hu¹, Victoria M McLeod², John F Quinn¹, Christopher J H Porter¹, Michael R Whittaker³, Lisa M Kaminskas⁴, Thomas P Davis⁵

Affiliations

¹ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052; Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052.
² Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052.
³ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052; Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052. Electronic address: [email protected].
⁴ Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052. Electronic address: [email protected].
⁵ ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052; Drug Delivery Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia, 3052; Department of Chemistry, University of Warwick, Coventry, ULCV4 7AL, UK. Electronic address: [email protected].

PMID: 26852861
DOI: 10.1016/j.xphs.2015.11.038

Abstract

PolyPEG star polymers have potential utility as cost-effective polymeric drug delivery vehicles, and as such, it is important to develop an understanding of their biopharmaceutical behavior. Moreover, although a number of studies have evaluated the utility of PolyPEG stars in vitro, investigation of these novel materials in vivo has been limited. Herein, we evaluated the pharmacokinetics of a 64 kDa tritiated PEG-based star polymer after subcutaneous and pulmonary administration in rats. After subcutaneous administration, the star polymer showed near complete bioavailability (∼80%) and a similar organ biodistribution profile to the polymer after intravenous administration. After intratracheal instillation to the lungs, the star polymer showed limited bioavailability (∼3%), and most of the administered radiolabel was recovered in lung tissue and feces after 6 d. The data reported here suggest that star polymers display similar pharmaceutical behavior to PEGylated dendrimers after subcutaneous and inhaled delivery and may therefore be used as similar, but more cost-effective drug delivery vehicles.

Keywords: PEG; bioavailability; biodistribution; nanoparticles; pharmacokinetics; pulmonary; star polymers; subcutaneous.

Publication types

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

MeSH terms

Administration, Inhalation
Animals
Biological Availability
Biopharmaceutics
Bronchoalveolar Lavage Fluid
Drug Delivery Systems
Feces / chemistry
Injections, Subcutaneous
Lung / metabolism
Male
Polyethylene Glycols / pharmacokinetics*
Rats
Rats, Sprague-Dawley
Tissue Distribution

Substances

Polyethylene Glycols