Comparing human peritoneal fluid and phosphate-buffered saline for drug delivery: do we need bio-relevant media?
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.
KeywordsIntraperitoneal Biological fluid In vivo-in vitro correlation Surgical Composition Rheology Solubility Dissolution
We would like to thank the Faculty of Medical and Health Sciences, The University of Auckland, for providing scholarship to Mr Prabhat Bhusal. We would also like to thank The Auckland Medical Research Foundation (AMRF) for supporting this research project.
Compliance with ethical standards
Conflict of interest
Prabhat Bhusal, Jamie Lee Rahiri, Bruce Sua, Jessica E. McDonald, Mahima Bansal, Sara Hanning, Manisha Sharma, Kaushik Chandramouli, Jeff Harrison, Georgina Procter, Gavin Andrews, David S. Jones, Andrew G. Hill and Darren Svirskis declare that they have no conflict of interest.
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