Biocompatible poly(ethylene succinate) polyester with molecular weight dependent drug release properties

Mohamed M Abdelghafour; Ágoston Orbán; Ágota Deák; Łukasz Lamch; Éva Frank; Roland Nagy; Szilveszter Ziegenheim; Pál Sipos; Eszter Farkas; Ferenc Bari; László Janovák

doi:10.1016/j.ijpharm.2022.121653

Biocompatible poly(ethylene succinate) polyester with molecular weight dependent drug release properties

Int J Pharm. 2022 Apr 25:618:121653. doi: 10.1016/j.ijpharm.2022.121653. Epub 2022 Mar 9.

Authors

Affiliations

¹ Department of Physical Chemistry and Materials Science, University of Szeged, H-6720, Rerrich Béla tér 1, Szeged, Hungary; Department of Chemistry, Faculty of Science, Zagazig University, Zagazig 44519, Egypt.
² Department of Physical Chemistry and Materials Science, University of Szeged, H-6720, Rerrich Béla tér 1, Szeged, Hungary.
³ Department of Organic and Pharmaceutical Technology, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
⁴ Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
⁵ Department of MOL Department of Hydrocarbon and Coal Processing, Faculty of Engineering, University of Pannonia, Egyetem Str. 10, H-8200 Veszprém, Hungary.
⁶ Department of Inorganic and Analytical Chemistry, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.
⁷ Department of Medical Physics and Informatics, Faculty of Medicine & Faculty of Science and Informatics, University of Szeged, Korányi Fasor 9, H-6720 Szeged, Hungary; HCEMM-USZ Cerebral Blood Flow and Metabolism Research Group, University of Szeged, Dugonics Square 13, H-6720 Szeged, Hungary; Department of Cell Biology and Molecular Medicine, Faculty of Science and Informatics & Faculty of Medicine, University of Szeged, Somogyi Str. 4, H-6720 Szeged, Hungary.
⁸ Department of Medical Physics and Informatics, Faculty of Medicine & Faculty of Science and Informatics, University of Szeged, Korányi Fasor 9, H-6720 Szeged, Hungary.
⁹ Department of Physical Chemistry and Materials Science, University of Szeged, H-6720, Rerrich Béla tér 1, Szeged, Hungary. Electronic address: janovakl@chem.u-szeged.hu.

PMID: 35278604
DOI: 10.1016/j.ijpharm.2022.121653

Abstract

In the present study, we demonstrate that well-known molecular weight-dependent solubility properties of a polymer can also be used in the field of controlled drug delivery. To prove this, poly(ethylene succinate) (PES) polyesters with polycondensation time regulated molecular weights were synthesized via catalyst-free direct polymerization in an equimolar ratio of ethylene glycol and succinic acid monomers at 185 °C. DSC and contact angle measurements revealed that increasing the molecular weight (M_w, 4.3-5.05 kDa) through the polymerization time (40-80 min) increased the thermal stability (T_m= ∼61-80 °C) and slightly the hydrophobicity (Θ_w= ∼27-41°) of the obtained aliphatic polyester. Next, this biodegradable polymer was used for the encapsulation of Ca²⁺ channel blocker Nimodipine (NIMO) to overcome the poor water solubility and enhance the bioavailability of the drug. The drug/ polymer compatibility was proved by the means of solubility (δ) and Flory-Huggins interaction (miscibility) parameters (χ). The nanoprecipitation encapsulation of NIMO into PES with increasing M_w resulted in the formation of spherical 270 ± 103 nm NIMO-loaded PES nanoparticles (NPs). Furthermore, based on the XRD measurements, the encapsulated form of NIMO-loaded PES NPs showed lower drug crystallinity, which enhanced not only the water solubility but even the water stability of the NIMO in an aqueous medium. The in-vitro drug release experiments demonstrated that the release of NIMO drug could be accelerated or even prolonged by the molecular weights of PES as well. Due to the low crystallinity of PES polyester and low particle size of the encapsulated NIMO drug led to enhance solubility and releasing process of NIMO from PES with lower M_w (4.3 kDa and 4.5 kDa) compared to pure crystalline NIMO. However, further increasing the molecular weight (5.05 kDa) was already reduced the amount of drug release that provides the prolonged therapeutic effect and enhances the bioavailability of the NIMO drug.

Keywords: Biocompatible polyester; Different molecular weight; Drug release control; Nimodipine; Poly(ethylene succinate).

MeSH terms

Drug Carriers / chemistry
Drug Liberation
Molecular Weight
Nanoparticles* / chemistry
Nimodipine
Particle Size
Polyesters* / chemistry
Polyethylene Glycols / chemistry
Polyethylenes
Polymers
Succinates
Water

Substances

Drug Carriers
Polyesters
Polyethylenes
Polymers
Succinates
poly(ethylene succinate)
Water
Polyethylene Glycols
Nimodipine