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Keywords:

  • Nephrotoxicity;
  • Liposomes;
  • Drug delivery;
  • Cationic polyprenoid;
  • Renal haemodynamics

Potential toxicity of a cationic derivative of polyprenol (APren-7) with lipofecting activity was examined, especially its influence on renal haemodynamics and function, in order to conduct further investigation of its suitability as a component of liposomal drug carriers. Sprague–Dawley rats received daily injections (0.5 mL, s.c.) of liposomes comprised of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) and APren-7 (LP); classic liposomes composed of DOPE only (L); water solvent (W). After 4 weeks rats were anaesthetised and a wide spectrum of functional parameters were measured. These included mean arterial blood pressure (MBP), total renal blood flow (RBF), renal cortical, outer and inner medullary blood flow (CBF, OMBF, IMBF, respectively), diuresis, and sodium and solute excretion. Most parameters did not significantly differ between treated and control groups. A lower OMBF/IMBF ratio in liposome-treated groups (L: 1.0 ± 0.1; LP: 1.1 ± 0.1 vs. W: 1.9 ± 0.3, p < 0.05) might be an early sign of renal function impairment, however, since the lowering occurred in both L and LP groups, there was no reason to suspect that APren-7 had any untoward influence on renal haemodynamics or excretion. The present results did not reveal toxic effects of APren-7 in experimental rats, indicating that it could be suitable as a component of liposomal drug carriers.

Practical applications: Many currently used drugs have severe side effects, which present a serious problem in the treatment of numerous diseases. Searching for compounds augmenting efficacy of drugs to reduce their dosage seems to be a promising strategy. This can be accomplished by facilitating the bioavailability of the drug, e.g. by improving penetration of biological membranes or delivery to the areas distant from the lumen of blood vessels and in particular instances by improving drug stability. The cationic derivative of polyprenol APren-7 has lipofecting properties. In this study we found APren-7 to be harmless to the experimental animals. Newly designed liposomal carriers could find application not only in the pharmaceutical and cosmetics industry but also in biological laboratories and in molecular medicine. ejlt201300489-gra-0001