Abstract:
The Pheroid® drug delivery system is now on the threshold of progressing into human clinical trials for various patented pharmaceutical applications and a systematic investigation of its toxicological properties in vitro and in vivo is thus a priority. Colloidal dispersions (nano- and microemulsions) demonstrate the ability to be adapted to accommodate either lipophilic, hydrophilic or amphiphilic drug molecules. The colloidal dispersions investigated during this evaluation has a general size of 200 nm - 2 μm, a zeta-potential of -25 mV and the main ingredient was ethyl esters of essential fatty acids.
The Ames mutagenicity assay was performed on selected Salmonella thyphimurium strains TA98, TA100 and TA102. The Ames assay included S9 metabolic activation and no mutagenicity was present during the assay. The effect of acute and subchronic administration on a biological system was investigated in two species of rodent (BALB/c mice and Sprague-Dawley rats). Observations focused on the physical condition, blood biochemical analysis and the haematological profiles. Gross necropsy was performed on all the test animals. Organ weights followed by histopathology of selected organ tissues were recorded.
During the acute evaluation animals showed tolerance of the maximum prescribed dose of 2000 mg/kg (according to OECD guidelines) in two rodent species after intravenous administration (absolute bioavaibility). The oral formulation was tolerated without incidents in both acute and subchronic studies. Although valuable baseline safety data was obtained regarding the Pheroid® system, future studies with the entrapped active pharmaceutical ingredients is necessary to provide a definitive safety profile.
