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

David Juriga, Istvan Laszlo, Krisztina Ludanyi, Imre Klebovich, Chang Hoon Chae, Miklos Zrinyi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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. Statement of Significance: 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.

Original languageEnglish
JournalActa Biomaterialia
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Prodrugs
Dopamine
Kinetics
Polymers
Pharmaceutical Preparations
Solubility
Bromelain
polydopamine
Bromelains
Dopamine Agents
Biodegradable polymers
Ethanolamine
Biodegradability
Chymotrypsin
Drug Delivery Systems
Drug delivery
Biocompatibility
Human Body
Reaction rates
Half-Life

Keywords

  • Dopamine
  • Higuchi model
  • Poly(aspartamide) drug conjugate
  • Poly(succinimide) prodrug
  • Prolonged release

ASJC Scopus subject areas

  • Biotechnology
  • Biomaterials
  • Biochemistry
  • Biomedical Engineering
  • Molecular Biology

Cite this

Kinetics of dopamine release from poly(aspartamide)-based prodrugs. / Juriga, David; Laszlo, Istvan; Ludanyi, Krisztina; Klebovich, Imre; Chae, Chang Hoon; Zrinyi, Miklos.

In: Acta Biomaterialia, 01.01.2018.

Research output: Contribution to journalArticle

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AU - Zrinyi, Miklos

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