Liliana Tarţău 1, R.V. Lupuşoru 2, D. Bindar 3, V. Melnig 3
1 Pharmacology – Algesiology Department, Gr. T. Popa University of Medicine and Pharmacy, Iaşi, Romania
2 Pathophysiology Department, Gr. T. Popa University of Medicine and Pharmacy, Iaşi, Romania
3 Department of Physics – COMB Laboratory, Faculty of Physics, Al. I. Cuza University, Iaşi, Romania
Abstract
Nanoparticles designed for drug delivery are defined as submicrometer-sized colloidal particles in which the active principle is dissolved, entrapped or encapsulated, and to which the active principle is absorbed or attached. Generally, nanoparticles can be used to provide targeted delivery of active substances, to sustain drug effect in target tissue, to decrease its adverse effects. Ketoprofen is one of the most potent non-steroidal anti-inflammatory drug frequently prescribed worldwide. Literature data describe various possibilities for the design of ketoprofen nanoparticulate formulations, which are characterized and studied regarding active substances’ delivery, but only a few were investigated for the in vivo effects. Aim: This study investigated the effects of ketoprofen lipid vesicles in a visceral pain model in mice. Method: The soft matter vesicles made of lipid-ketoprofen-chitosan were prepared using an original method, and were physicochemically analyzed using a Malvern Zetasizer Nano ZS, ZEN-3500 model. The experiments were carried out on white Swiss mice (20-25 g), divided into 3 groups of 7 animals each, treated orally: Group I (Control): distilled water 0.3 ml, Group II (KET): 15 mg/kbw ketoprofen, Group III (KET-ves): 15 mg/kbw ketoprofen entrapped in vesicles. The nociceptive visceral testing was performed using the mouse model of acute pain writhing test. The experimental protocol was implemented according to the recommendations of the University Committee for Research and Ethical Issues, and to the guidelines of IASP Committee for Research and Ethical Issues. The data were statistically analyzed with SPSS software for Windows version 17.0 and ANOVA method. Results: It was demonstrated that the soft matter vesicles are capable to entrap ketoprofen water solution, with a large efficiency. The vesicles’ dimensions vary from tens of nanometers to hundreds, and the solution has a moderate stability. Oral administration of ketoprofen resulted in a decrease of behavioral manifestations induced by chemical noxious stimuli, statistically significant immediately in the experiment, effect present for 120 minutes. Using soft vesicles entrapping ketoprofen, we obtained the reduction of writhes number with an onset at 3 hours and prolonged for 5 hours after substance administration. Conclusions: The use of soft matter vesicles as carriers for ketoprofen presented the advantage of drugs’ sustained release, compared to nonentrapped substances in the writhing test.