PhD Scientific Days 2018

Budapest, April 19–20, 2018

Synthesis and investigation of biodegradable poly(amino acid) based nano drug-delivery systems

Juriga, Dávid

David Juriga1, Peter Laskawy1, Krisztina Toth1, Zeliha Güler2, Krisztina Ludanyi3, Angela Jedlovszky-Hajdu1, Krisztina Nagy4, Sezai A. Sarac2, Gabor Varga4, Imre Klebovich3, Miklos Zrinyi1
1) Department of Biophysics and Radiation Biology, Semmelweis University, Budapest
2) Department of Chemistry, Istanbul Technical University, Istanbul
3) Department of Pharmacy, Semmelweis University, Budapest
4) Department of Oralbiology, Semmelweis University, Budapest

Language of the presentation

English

Text of the abstract

Drug-polymer conjugates or prodrugs are novel class of polymer drug delivery systems (pDDSs) for effective drug administration. Stimuli responsive (such as pH, presence of the enzymes etc.) attribute of pDDSs control the release kinetics that can maintain the drug level with just a single dosage. Furthermore protection of the drug from deactivation as well as from premature degradation, minimization of the cytotoxicity and enhancing tissue compatibility can be achieved.
Several polymers have been recently investigated as candidates for polymeric prodrugs. For good polymer candidate it is essential that the polymer used is neither inherently toxic nor immunogenic whereas biodegradability is also favorable. Release of drug or drug analogues from the macromolecular backbone might be induced either by chemical or by enzymatic reactions.
As several enzymes can be found in the human body which cleaves amide bonds, poly(amino acids) are promising candidates to prepare polymer-drug conjugates. In this work poly(aspartamide) based conjugates were synthesized with different chemical constitutions with dopamine as conjugated drug. The conjugates were synthesized from poly(succinimide) by nucleophilic addition. The drug release from the different conjugates was investigated in the presence of different enzymes and the kinetics of release was described. To prepare drug delivery system oppositely charged polymers were synthesized from poly(succinimide). Oppositely charged poly(α-amino acid)-based polyelectrolytes interact electrostatically forming polymer nanocomplexes with a diameter 100-200 nm. The size and the shape of the nanocomplexes were characterized by DLS and different microscopic techniques. The pH and salt concentration dependent stability and membrane permeability were investigated as well. The drug release kinetics was monitored by UV-VIS spectroscopy in different environments.
This research was supported by the UNKP-17-3-III-SE-17 new national excellence program of the ministry of human capacities and by the OTKA Foundation (Grant No. K115259 and FK124147).

Data of the presenter

Doctoral School: Pharmaceutical Sciences
Program: Experimental and Clinical Pharmacology
Supervisor: Miklós Zrínyi
E-mail: juriga.david@med.semmelweis-univ.hu