A water soluble bioconjugate of piroxicam and arabinogalactan sulfate possessing high antiinflammatory activity was obtained for the first time.Piroxicam, 4 hydroxy 2 methyl 3 [N (pyridin 2 yl) carboxamide 2H 1,2 benzothiazine 1,1 dioxide (1), is a nonsteroid highly efficient antiinflammatory, analgesic, and antipyretic pharmaceutical agent. 1 It differs from the known antiinflammatory analogues (Indomethacin, Volt aren (Diclofenac), Ibuprofen) by higher analgesic and anti pyretic activities (7-60 times), efficiency in small dozes (daily doze 20 mg), prolonged effect, and good tolerabili ty. Piroxicam is intended for the treatment of the muscu loskeletal system diseases, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, the Bekhterev disease, acute attacks of gout. At the present time, piroxicam is used to replace opioid analgesics in postoperative period, 2 as well as in cancer chemotherapy. 3-5 The agent has good characteristics of membrane permeability, but because of low solubility in water (0.003% at pH 5, 37 C) it slowly dissolves in the gastrointestinal tract (GIT), which can cause an irritating effect on the latter.An improvement of bioaccessability and clinical effi ciency of poorly soluble in water lipophilic drugs upon oral intake (administration) is an actual problem. The most popular approaches to the increase of the solubility of such agents, in particular piroxicam, in water and biologi cal liquids at the physiological pH values are based on the mixing the drugs with excipients (oil, surfactants); trans formations to emulsions 6-8 and preparation of solid dis persions based on the inclusion complexes with cyclo dextrin, 2,9-10 polyvinylpyrrolidone, 11,12 phospholipids, 13 and poly(ethylene glycols); 14,15 preparation of cocrystals with pharmaceutically acceptable acids. 16,17We have developed an original, resources saving tech nology for the preparation of piroxicam, which possesses a number of significant advantages over foreign technolo gies (a two step process as compared to the known four and five step procedures). 18, 19 It was shown that the use of the mechano chemical method for the immobilization of piroxicam on chitosan, cellulose, 20-22 metal oxides 23 makes it possible to increase the solubility in water of obtained nanocomposites, helps to protect the drug from oxidation, stabilizes its metastable active state in the ma trix and increases the rate of agent release that can facili tate its biological accessibility.In order to develop new highly efficient nanostruc tured modifications of piroxicam with increased bio accessability and decreased side effect, we for the first time synthesized a bioconjugate of piroxicam and ara binogalactan sulfate.
Results and DiscussionIn the last years, the use of biopolymers as a matrix for the preparation of pharmaceutical forms with prolonged effect, controlled release of the medicine, and targeted delivery to a certain organ become more and more actu al problem.Arabinogalactan (AG) is a naturally occurring hetero polysacchari...
