Format

Send to

Choose Destination
Drug Deliv Transl Res. 2018 Jun;8(3):708-718. doi: 10.1007/s13346-018-0513-9.

Comparing human peritoneal fluid and phosphate-buffered saline for drug delivery: do we need bio-relevant media?

Author information

1
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, Auckland, 92019, New Zealand.
2
Department of Surgery, South Auckland Clinical Campus, Faculty of Medical and Health Sciences, Middlemore Hospital, The University of Auckland, Auckland, New Zealand.
3
School of Pharmacy, Queen's University Belfast, Belfast, UK.
4
School of Pharmacy, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag, Auckland, 92019, New Zealand. d.svirskis@auckland.ac.nz.

Abstract

An understanding of biological fluids at the site of administration is important to predict the fate of drug delivery systems in vivo. Little is known about peritoneal fluid; therefore, we have investigated this biological fluid and compared it to phosphate-buffered saline, a synthetic media commonly used for in vitro evaluation of intraperitoneal drug delivery systems. Human peritoneal fluid samples were analysed for electrolyte, protein and lipid levels. In addition, physicochemical properties were measured alongside rheological parameters. Significant inter-patient variations were observed with regard to pH (p < 0.001), buffer capacity (p < 0.05), osmolality (p < 0.001) and surface tension (p < 0.05). All the investigated physicochemical properties of peritoneal fluid differed from phosphate-buffered saline (p < 0.001). Rheological examination of peritoneal fluid demonstrated non-Newtonian shear thinning behaviour and predominantly exhibited the characteristics of an entangled network. Inter-patient and inter-day variability in the viscosity of peritoneal fluid was observed. The solubility of the local anaesthetic lidocaine in peritoneal fluid was significantly higher (p < 0.05) when compared to phosphate-buffered saline. Interestingly, the dissolution rate of lidocaine was not significantly different between the synthetic and biological media. Importantly, and with relevance to intraperitoneal drug delivery systems, the sustained release of lidocaine from a thermosensitive gel formulation occurred at a significantly faster rate into peritoneal fluid. Collectively, these data demonstrate the variation between commonly used synthetic media and human peritoneal fluid. The differences in drug release rates observed illustrate the need for bio-relevant media, which ultimately would improve in vitro-in vivo correlation.

KEYWORDS:

Biological fluid; Composition; Dissolution; In vivo-in vitro correlation; Intraperitoneal; Rheology; Solubility; Surgical

PMID:
29582351
DOI:
10.1007/s13346-018-0513-9
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center