Preparatıon and Application of Biocompatible Carrier Implant to be Used in the Controlled Acquisition of Digoxin
In this study, a persistent system is aimed to be established which contributes to slow basal digoxin release in the treatment of cardiac failure. Poly(2-hydroxyethyl-metacrylate-methylmetacrylate) (p(HEMA-MMA) copolymer that can swell by taking on water is prepared in cylindirical form by UV photopolymerization method for the controlled-release of digoxin and effective hydrogel implant formulation. A batch of p(HEMA-MMA) composition is prepared in different monomer ratios. Biocompatibility is improved by adding PEO, PEG and serum albumine to the structures of p(HEMA-MMA), respectively. Scanning electron microscope (SEM) studies are carried out for the surface structure of the prepared carrier implant material and differential scanning calorimetry (DSC) studies for the thermal stability analysis. Swelling behaviors are investigated by transferring solvent molecules to the hydrogels. Digoxin release kinetics are evaluated by applying three different accumulative digoxin doses (100, 250 and 500 U/mL) in the persistent flow release system containing physiological phosphate. Power law, level-zero, and Higuchi model equations are utilized so as to evaluate the release mechanism of digoxin. The most suitable results are acquired from the composition whose HEMA:MMA monomer ratio is 1:0.5 (v/v) in drug accumulation and release studies. It is observed from the SEM image that the carrier implant in the structure of the acquired hydrogel has a smooth surface. According to DSC results, it is seen that thermal stability decreases in the event that MMA comonomer is added to the structure of the pHEMA hydrogel. Balance water amount within the physiological phosphate buffer of the p(HEMA-MMA) copolymer is observed to be less than the pHEMA. Digoxin release loaded to carrier implants by different ratios takes a long-term period as expected. It is decided that the formulation established in the study can be successfully applied for the basal digoxin level over four weeks in the treatment of chronic cardiac failure.
Dickstein K, Cohen-Solal A, Filippatos G, McMurray JJ, Ponikowski P, Poole-Wilson PA, Strömberg A, van Veldhuisen DJ, Atar D, Hoes AW, Keren A, Mebazaa A, Nieminen M, Priori SG, Swedberg K; ESC Committee for Practice Guidelines (CPG). ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC [HFA] and endorsed by the European Society of Intensive Care Medicine [ESICM]. Eur J Heart Fail 2008;10:933-89. DOI: 10.1016/j.ejheart.2008.08.005.
Digitalis Investigation Group.The effect of digoxin on mortality and morbidity in patients with heart failure. The Digitalis Investigation Group. N Engl J Med 1997;336:525-33. DOI:10.1056/NEJM199702203360801.
Langer RS ve Peppas NA. Present and future applications of biomaterials in controlled drug delivery systems. Biomaterials 1981;2:201-14. DOI: 10.1016/0142-9612(81)90059-4.
Byrne ME, Park K, Peppas NA. Molecular imprinting within hydrogels. Adv Drug Deliv Rev. 2002 ;54(1):149-61. Review. DOI:10.1016/S0169-409X(01)00246-0.
Arıca MY, Bayramoğlu G, Bıçak N. Characterization of tyrosinase immobilised onto spacer-arm attached glycidyl methacrylate-based reactive microbeads. Process biochemistry. 2004;39: 2007-2017. DOI:10.1016/j.procbio.2003.09.030.
Arıca MY. Epoxy-Derived pHEMA Membrane for Use Bioactive Macromolecules Immobilization: Covalently Bound Urease in a Continuous Model System. Journal of Applied Polymer Science. 2000;77:2000-2008. DOI: 10.1002/1097-4628(20000829)77:9<2000::AID-APP16>3.0.CO;2-M
Svec F, Fréchet JM. Modified poly(glycidyl methacrylate-co-ethylene dimethacrylate) continuous rod columns for preparative-scale ion-exchange chromatography of proteins. J Chromatogr A. 1995;70289-95. DOI: 10.1016/0021-9673(94)01021-6.
Blanco R, Arai A, Grinberg N, Yarmush DM, Karger BL. Role of association on protein adsorption isotherms. Beta-lactoglobulin A adsorbed on a weakly hydrophobicsurface. J Chromatogr. 1989 Nov 17;482:1-12. DOI: 10.1016/S0021-9673(01)93202-9.
Mykhaylyk TA, Evans SD, Fernyhough CM, Hamley LW, Henderson JR. Ellipsometric study of adsorption on nanopatterned block copolymer substrates. J. Chem. Phys. 2005;122: 104902. DOI: 10.1063/1.1860371.
Zisman WA. Influence Of Constitution On Adhesion. Ind. Eng. Chem. 1963;55:18-38. DOI: 10.1021/ie50646a003.
Van Oss CJ, Good RJ, Chaudhury MK. Additive and nonadditive surface tension components and the interpretation of contact angles. Langmiur 1988;4:884-891. DOI: 10.1021/la00082a018
Peppas NA, Huang Y, Torres-Lugo M, Ward JH, Zhang J. Physicochemical foundations and structural design of hydrogels in medicine and biology. Annu Rev Biomed Eng. 2000;2:9-29. DOI: 10.1146/annurev.bioeng.2.1.9.
Siepmann J, Peppas NA. Modeling of drug release from delivery systems based on hydroxypropyl methylcellulose (HPMC). Adv Drug Deliv Rev. 2001;48:39-57. Review. DOI: 10.1016/s0169-409x(01)00112-0.
Ritger PL, Peppas NA. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J. Controlled Release. 1987;5:37-42. DOI:10.1016/0168-3659(87)90035-6.
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. Int. J. Pharm 1983;15:25-35. doi:10.1016/0378-5173(83)90064-9.
Hıguchı T. Mechanism of Sustained Action Medication. Theorethical Analysis Of Rate of Solid Drugs Dispersed in Solid Matrices. J. Pharm. Sci. 1963;52:1145-1149. DOI: 10.1002/jps.2600521210.
J. Turk. Chem. Soc., Sect. A: Chem.