Efficacy of liposomal forms of cytostatics

Abstract

Study of the toxicity and pharmacokinetics of free and liposomal forms of cytostatics revealed an appreciable decrease of the toxicity of high drug doses and prolongation of drug action in liposomes. The distribution of drugs in organs and tissues is shown.

Some aspects of the technology for liposomal medicinal preparations

“…On the other hand, the introduction of acid phospholipids (e.g., diphosphatidylglycerols) into liposomes increased by 8-12% the content of anthracyclines. The oxidation index of the loaded liposomes did not exceed 0.37 -0.42 [3,4].…”

“…Note that this operation provides simultaneous standardization of the liposomal preparations with respect to particle size. Data reported in [3,4,32] indicate that filters with a pore size of 0.22 gm may be used for the filtration of tiposomes characterized by particle size ranging from 0.1 to 0.35 lain. The loss ofliposomes does not exceed 1 -3% and the resulting preparations contain liposomes sized 160 -240 nm.…”

“…Stability of the lipid-encapsulated drug complex is achieved by freeze-drying in the presence of cryoprotectors. The resulting dehydrated liposomal preparations are readily stored and retain more than 90% of the drug component upon rehydration [2,3,36]. For example, a dehydrated liposomal form of doxorubicin was successfully stored in a lyophile-dry state for longer than one year [2,3].…”

“…It was demonstrated that optimum conditions for obtaining unloaded liposomes by extrusion involve pressures of (5.8-6.2) x 107 Pa and temperatures of 30 -35~ which provide for the formation of liposomes with standard compositions. The major fraction of particles (up to 90%) is characterized by dimensions in the range of 160 -240 nm and an oxidation index not exceeding 0.4 (against 0.25 in the initial phosphatidylcholines) [1], which is obviously superior to the phosphatidylcholine liposomes obtained by sonification (where the oxidation index is as high as 0.7 -0.9) [1,3,4]. The characteristics of liposomes obtained by extrusion (preset particle size, low degree of phospholipid oxidation, absence of hydrolysis products) allow them to be used as carriers in preparations for intravenous injection.…”

The study of the lipid membrane charge effect when creating liposomes with oxaliplatin

“…One of the ways for reducing toxicity of cytostatics is their incorporation into liposomes -nanoparticles composed of the lipid bilayer surrounding the internal cavity with the aqueous medium inside. Liposomal cytostatics have the lower level of cardiotoxicity, less myelosuppression and less severe other side effects [4,7].…”