How we risk: liposomes and steroids

The fight against the illicit use of doping substances and methods to produce an unfair advantage in sport is a race against time. A substance or a method shall be included in the Prohibited List also in the case there is medical or other scientific evidence that the substance or method has the potential to mask the use of other prohibited substances or prohibited methods [1]. In this work, which follows a preliminary study whose results have already been presented [2] the potential masking effect of liposomes on the detestino of androgenic anabolic steroids (AAS) has been investigate. Steroids were chosen as drugs model since they still represent the most abused class of performance-enhancing drugs. Liposomes are artificial vesicles composed of lipid bilayers. They typically consist of phospholipids such as phosphatidylcholine and phosphatidylglycerol and colesterolo, a waxy steroid. Since liposomes were first described, in 1961, the attention of scientists in different areas of research focused on their ability to encapsulate large amounts of both small molecules and proteins. They were also stupide as models of cell membranes[3]. In pharmaceutics, nano-sized liposomes are mainly utilized as drug delivery systems (DDSs). Compounds which in a classical route of administration could lead to severe toxicity (like intravenous solution of antitumor drugs) often showed a relevant improvement in their therapeutic index when they are administered as liposomal formulations[4].In this case, the pharmacokinetics (PK) of the carried drug becomes secondari to that of the carrier. Since liposomes can potentially circulate in the blood in a stable form and do not undergo glomerular filtration, the drug would be released slowly and for longer time. This leads to a decrease of metabolic deactivation and renal excretion, and allows for the use of lower doses and less toxic treatments. Theoretically, liposomes can mask steroid abuse in doping acting both as “body-oriented” masking agents, modulating the PK of the drugs (like diuretics do), or as “lab-oriented”, interfering indirectly with the analytical methods (like proteases do). Several potential actions were investigated: ‐ potential effect of a liposome-based formulation for slow release of anabolic steroide (testosterone) on the steroid pharmacokinetic ‐ post-formation interaction of empty liposomes with steroide, particularly glucuronated metabolites (norandrosterone glucuronide (NAG) and noretiocholanolone glucuronide (NEG), main urinary metabolites of nandrolone ‐ effects on the GC-MS quantitative analysis of NAG and NEG Finally, several analytical strategies to detect liposome-based formulations in biological fluids and/or to minimize their masking effect were considered