Cationic derivative of polyprenol, a potential component of liposomal drug carriers, does not alter renal function in rats

Abstract

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 AE 0.1; LP: 1.1 AE 0.1 vs. W: 1.9 AE 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.Abbreviations: APren, cationic derivative of polyisoprenoid alcohol; DOPE, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; IMBF, inner medullary blood flow; MBP, mean arterial blood pressure; OMBF, outer medullary blood flow; RBF, total renal blood flow Eur.

Identification of Abies sibirica L. Polyprenols and Characterisation of Polyprenol-Containing Liposomes

“…Analytically speaking, the most thoroughly studied isoprenoid structures seem to be those extracted from Ginkgo biloba [34] plausibly due to plant's high popularity in the Eastern traditional medicine. Apart from that, there are several studies that examine polyisoprenoid-containing bilayer lipid membrane models [35][36][37] and liposomal formulations [38]. All the accumulated research notwithstanding, there are still only a few commercial polyprenol formulations such as Ropren ® [39], Fortepren ® [3], and antiviral polyprenol aerosol [40] available on the market today, and thus we wished to explore the potential of such polyprenol preparations further.…”

Prenyl Ammonium Salts – New Carriers for Gene Delivery: A B16-F10 Mouse Melanoma Model

“…Worth noting is the protective effect of DOPE, used as the component of the transfection mixture, on cell proliferation. Moreover, Gawrys et al [ 15 , 16 ] showed in in vivo experiments, that AP-7/DOPE liposomes did not affect, after subcutaneous administration, the overall condition, behaviour nor the function of the cardiovascular and renal excretory system of rats. Though in our cell-line studies AP-7 influenced B16-F10 cell proliferation, it seems that this compound and hopefully other Amino-Prenols too, are non-toxic for living organisms and can be used in various applications.…”

“…As a result good efficacy of in vitro transfection with application of AP-7-based (aminoprenol composed of seven isoprene units) complexes has been demonstrated [ 10 ]. Further studies on AP-7 as a drug carrier in rats revealed liposomes containing AP-7 to be harmless to the experimental animals [ 15 ]. AP-7 containing liposomes did not affect functions of the excretory and cardiovascular systems, nor renal morphology [ 16 ].…”

Chymase Dependent Pathway of Angiotensin II Generation and Rapeseed Derived Peptides for Antihypertensive Treatment of Spontaneously Hypertensive Rats

“…In acute experiments rats were anesthetized with intraperitoneal (ip) sodium thiopental (100 mg/kg; Sandoz GmbH, Kundl, Austria), which provided stable anesthesia for about 4 h. All surgical preparations were already described in detail (Gawrys et al, 2014;Badzynska et al, 2020). Throughout the experiment the temperature of the animal was kept constant (37°C).…”