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Design and characterization of nanoparticles as platforms for delivery of curcumin Elena Drakalska1,2, Denitsa Momekova2, Stanislav Rangelov3, Nikolay Lambov2 1 University “Goce Delchev”- Stip, Faculty of medical sciences 2 Faculty of Pharmacy, Medical University of Sofia, 2 Dunav St., 1000 Sofia, Bulgaria 3 Institute of Polymers, Bulgarian Academy of Sciences, 103 Acad. Georgi Bonchev St., 1113 Sofia, Bulgaria E-mail: [email protected] INTRODUCTION Curcumin, the active polyphenol isolated from Curcuma Longa, exhibited potent pleiotropic antineoplastic activity and low nonspecific toxicity to normal cells. Unfortunately, the clinical realization of its potential is limited due to its extremely low aqueous solubility (11ng/ml), instability at physiological pH associated with low systemic bioavailability after oral administration (8g/kg). An intriguing approach to overcome these limitations is the design of nanosized vehicles for efficient delivery of curcumin. The present contribution is focused on newly-synthetized PEGylated tertbutylcalix[4]arene, used for preparation of various platforms for delivery of curcumin, such as inclusion complexes and supramolecular aggregates. The hydrophobic properties of curcumin allow it to be incorporated into CX[4]PEG. due to its amphiphilic nature. At concentration of 0.375 µmol/ml by far exceeding the critical micellar concentration, CX[4]PEG proved to drastically increased the solubility of curcumin -568 fold due to concomitant formation of inclusion complexes and supramolecular aggregates. The basic physicochemical characteristics of empty and curcumin loaded supramolcular aggregates are given in Table 1 EXPERIMENTAL Methods Solvent evaporation method Heating method FT-IR MTT Flow cytometry DLS RESULTS Curcumin Mixture Complex 110 0,4 100 90 0,3 80 Size distribution of a) CX[4]PEG free and b) CX[4]PEG curcumin loaded supramolecular aggregates 70 %T curcumin (mol/ml) heating method co-precipitation 0,2 60 50 40 0,1 30 20 0,0 10 0,0 0,1 0,2 0,3 CX[4]PEG (mol/ml) 0,4 4000 3500 3000 2500 2000 1500 1000 500 cm-1 Phase solubility diagrams of curcumin in aqueous complexation media containing various concentration of CX[4]arene. IR spectra of curcumin, curcumin – CX[4]arenes physical mixture and inclusion complex. Cytotoxicity study IC50 (μmol/L) (n=8) Formulations Curcumin (DMSO solution) PEG-CX-4 curcumin complexes aacute promyelocyte leukemia; KG-1a RPMI-8226b 13,45 2,31 2,89 0,77 8,70 1,44 2,22 0,79 bmultiple myeloma; CONCLUSION: On the grounds of the excellent in vitro biocompatibility profile and the favorable physicochemical and drug loading characteristics of the tested compounds, and their ability to retain the intrinsic pharmacological properties of encapsulated drug they could be considered promising drug delivery platforms for lipophilic curcumin ACKNOWLEDGEMENTS Financial support from National Science Fund of Bulgaria, Grant № ДФНИ Б01-25/2012 and ДЦВП 02-2/2009 is gratefully acknowledged.