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Synthesis of prolonged-release drugs for osteoplasty that are based on chemically modified calcium phosphates
Authors:V. S. Spiridonov  P. G. Mingalev  G. V. Lisichkin  A. V. Sklyarenko  D. E. Satarova  V. B. Kurochkina
Affiliation:(1) Department of Chemistry, Moscow State University, Vorob’evy gory, Moscow, 119992, Russia;(2) State Scientific Center of Antibiotics, ul. Nagatinskaya 3a, Moscow, 117105, Russia
Abstract:In order to use hydroxyapatite and other biocompatible calcium phosphates as carriers for local prolonged-release drug, it is necessary to have an active component capable of retaining the preparation deposited onto the carrier surface for a long time (at least, for a few days). The grafting of the layer of active functional groups onto the carrier surface is employed to affect kinetic adsorption-desorption characteristics of calcium phosphates. The method of chemical modification of biocompatible calcium phosphates that uses B(OC4H9)3, SiCl4, POCl3, PCl5, and SnCl4 is developed. The effect of the modification of calcium phosphate’s surface on the kinetics of hydrolytic desorption of octadecylamine and tetraethylenepentamine modeling the hydrophobic and hydrophilic drugs, respectively, as well as gentamicin, an antibiotic that is widely used in clinical practice to prevent and cure inflammation processes upon the damage of bony tissue, is studied. It is shown that the rate of desorption of these substances from calcium phosphates into the aqueous phase is significantly retarded when the carrier surface is preliminarily modified. By means of ESR and IR Fourier spectroscopy, the interaction of octadecylamine and tetraethylenepentamine with calcium phosphate’s surface is investigated. A conclusion about the existence of two mechanisms of adsorption of amines on modified calcium phosphates is drawn. The procedure for the preparation of biocompatible calcium phosphates with hemisorbed gentamicin is developed.
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