Kinetics of dopamine release from poly(aspartamide)-based prodrugs

• Published in: Acta biomaterialia Vol. 76; pp. 225 - 238
• Main Authors: Juriga, David, Laszlo, Istvan, Ludanyi, Krisztina, Klebovich, Imre, Chae, Chang Hoon, Zrinyi, Miklos
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2018; Elsevier BV
• Subjects: Biocompatibility; Biodegradability; Biodegradation; Chemical compounds; Chemical reactions; Chymotrypsin; Conjugates; Deactivation; Dopamine; Drug delivery; Drug delivery systems; Drugs; Higuchi model; Kinetics; Lipophilicity; Macromolecules; Organic chemistry; Parameters; Physical properties; Poly(aspartamide) drug conjugate; Poly(succinimide) prodrug; Polymers; Prodrugs; Prolonged release; Reaction kinetics; Solubility; Thermogravimetric analysis; Time dependence; Dopamine; Poly(aspartamide) drug conjugate; Prolonged release; Poly(succinimide) prodrug; Higuchi model
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2018.06.030

[Display omitted] Preparation of novel biocompatible and biodegradable polymer-based prodrugs that can be applied in complex drug delivery systems is one of the most researched fields in pharmaceutics. The kinetics of the drug release strongly depends on the physicochemical parameters of prodrugs as well as environmental properties, therefore precise kinetical description is crucial to design the appropriate polymer prodrug formula. The aim of the present study was to investigate the dopamine release from different poly(aspartamide) based dopamine drug conjugates in different environments and to work out a kinetic description which can be extended to describe drug release in similar systems. Poly(aspartamide) was conjugated with different amounts of dopamine. In order to alter the solubility of the conjugates, 2-aminoethanol was also grafted to the main chain. Chemical structure as well as physical properties such as solubility, lipophilicity measurements and thermogravimetric analysis has been carried out. Kinetics of dopamine release from the macromolecular prodrugs which has good water solubility has been studied and compared in different environments (phosphate buffer, Bromelain and α-Chymotrypsin). It was found that the kinetics of release in those solutions can be satisfactorily described by first order reaction rate. For poorly-soluble conjugates, the release of dopamine was considered as a result of coupling of diffusion and chemical reaction. Besides the time dependence of dopamine cleavage, a practical quantity, the half–life of the release of loading capacity has been introduced and evaluated. It was found, that dopamine containing macromolecular prodrugs exhibit prolonged release kinetics and the quantitative description of the kinetics, including the most important physical parameters provides a solid base for future pharmaceutical and medical studies. Poly(aspartamide) based polymer-drug conjugates are promising for controlled and prolonged drug delivery due to their biocompatibility and biodegradability. In this study different poly(aspartamide) based dopamine conjugates were synthesized which can protect dopamine from deactivation in the human body. Since there is no satisfying kinetics description for drug release from covalent polymer-drug conjugates in the literature, dopamine release was investigated in different environments and a complete kinetical description was worked out. This study demonstrates that poly(aspartamide) is able to protect conjugated dopamine from deactivation and provide prolonged release in alkaline pH as well as in the presence of different enzymes. Furthermore, detailed kinetical descriptions were demonstrated which can be used in case of other covalent polymer-drug conjugates.