International Journal of Pharmaceutics, 43 (1988) 267-271 Elsevier IJP 01474 267 Tissue distribution of polybutylcyanoacrylate nanoparticles carrying spin-labelled nitrosourea M. Simeonova 1, T. Ivanova 2, E. Raikova 3, MI Georgieva 4, Z. Raikov 3 I Scientific Industrial Centre for Special Polymers, Sofia (Bulgaria), 20ncological Research Institute, Sofia (Bulgaria), 3 Higher Institute of Medicine, Department of Chemistry and Biochemistry, Stara Zagora (Bulgaria), and 4 Higher Institute of Chemical Technology, Department of Technology of Plastic, Sofia (Bulgaria) (Received 5 February 1987) (Modified version received 17 November 1987) (Accepted 22 November 1987) Key words: Polybutylcyanoacrylate nanoparticles; Tissue distribution in mice; Spin-labelled nitrosourea; EPR spectroscopy. Summary The opportunities and advantages of EPR spectroscopy for studying tissue distribution of polyalkylcyanoacrylate nanoparticles are discussed. Tissue distribution of polybutyl-2-cyanoacrylate nanoparticles (PBCN) having diameters of about 100 nm, charged by 1-(2-chl0roethyl)-3-(1-oxyl-2,2,6,6-tetra-methylpiperidinyl)-l-nitrosourea (spin-labelled nitrosourea, SLCNU) is investigated in C57 Black mice, both healthy and tumor-bearing (subcutaneously implanted Melanom B16). PBCN modifies the tissue distribution profile of SLCNU; the kidney excretion rate is reduced to one third of normal; drug accumulation in the liver and in the brain is also reduced, and drug concentrations are lowered. An increased accumulation of SLCNU loaded PBCN in the tumor tissue is estimated. The interest in the polyalkylcyanoacrylate nanoparticles as colloidal drug transport carriers, continuously increases. This is reasonable taking into account their advantages: good biocompati- bility, biodegradation (Leyh et al., 1984; Lenaerts et al., 1984a), an ability for stable and reproduci- ble sorption of many drugs, an ability to lower drug toxicity (Couvreur et al., 1982) and improve therapeutic effect (Brasseur et al., 1980) of some anticancer preparations. Tissue distribution inves- tigations in animals show a strong and fast entrap- Correspondence: M. Simeonova, Scientific Industrial Centre for Special Polymers, 4a K1. Ohridski Street, 1156 Sofia, Bulgaria. ment by organs enriched with reticuloendothelial cells (Kante et al., 1980; Couvreur et al., 1980) and they can change tissue distribution profiles of the cytostatic drugs which they are charged with (Couvreur et al., 1980). Studies on the fate of this carrier in the body and its excretion ways are based on the radiolabelled nanoparticles (Couvreur et al., 1980; Lenaerts et al., 1984b; Grislain et al., 1983; Ilium et al., 1984; Kreuter et al., 1979; Kreuter et al., 1983). EPR spectroscopy is success- fully used in studying the pharmacokinetics of nanoparticles. In the present work we demonstrate the oppor- tunities and advantages of this method for tissue distribution investigations. This goal was attained