Intravenous Administration to Rabbits of Non-stealth and Stealth Doxorubicin-loaded Solid Lipid Nanoparticles at Increasing Concentrations of Stealth Agent: Pharmacokinetics and Distribution of Doxorubicin in Brain and Other Tissues

Abstract

The pharmacokinetics and tissue distribution of doxorubicin incorporated in non-stealth solid lipid nanoparticles (SLN) and in stealth solid lipid nanoparticles (SSLN) (three formulations at increasing concentrations of stearic acid-PEG 2000 as stealth agent) after intravenous administration to conscious rabbits have been studied. The control was the commercial doxorubicin solution. The experiments lasted 6 h and blood samples were collected at fixed times after the injections. In all samples, the concentration of doxorubicin and doxorubicinol were determined. Doxorubicin AUC increased as a function of the amount of stealth agent present in the SLN. Doxorubicin was still present in the blood 6 h after the injection of SLN or SSLN, while no doxorubicin was detectable after the i.v. injection of doxorubicin solution. Tissue distribution of doxorubicin was determined 30 min, 2 and 6 h after the administration of the five formulations. Doxorubicin was present in the brain only after the SLN administration. The increase in the stealth agent affected the doxorubicin transported into the brain; 6 h after injection, doxorubicin was detectable in the brain only with the SSLN at the highest amount of stealth agent. In the other rabbit tissues (liver, lungs, spleeen, heart and kidneys) the amount of doxorubicin present was always lower after the injection of any of the four types of SLN than after the commercial solution. In particular, all SLN formulations significantly decreased heart and liver concentrations of doxorubicin.

Artemisia arborescens L essential oil-loaded solid lipid nanoparticles for potential agricultural application: Preparation and characterization

“…SLN have been intensively investigated for dermal application, 4 parenteral 5,6 and peroral 7,8 administration, and ocular delivery. 9 However, only one article has been published to date for the use of SLN in agriculture.…”

Conventional Chemotherapeutic Drug Nanoparticles for Cancer Treatment

“…There was always less doxorubicin in the liver, lungs, spleen, heart and kidneys after injection of any of the types of SLNs than after the doxorubicin solution. In particular, all SLNs formulations significantly decreased heart and liver concentrations of doxorubicin [79]. Interestingly, both non-coated and coated SLNs showed a similar low uptake by liver and spleen macrophages [80].…”

Nanocarrier drugs in the treatment of brain tumors

“…The same study design, repeated in healthy rabbits, showed similar pharmacokinetic behavior and tissue distribution parameters. [43] Docetaxel-incorporated albumin-lipid nanoparticles (DNPs) in vitro induce apoptosis of several cancer cell lines, and in vivo, accumulate at the experimental glioma site. [44] This phenomenon is believed to be due to EPR effect.…”