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

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 degrees C. DSC and contact angle measurements revealed that increasing the molecular weight (Mw, 4.3-5.05 kDa) through the polymerization time (40-80 min) increased the thermal stability (T-m= similar to 61-80 C) and slightly the hydrophobicity (Theta(w)= similar to 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 (delta) and Flory-Huggins interaction (miscibility) parameters (chi). 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.

Automated summary

In this study, the molecular weight-dependent solubility properties of a polymer were used in the field of controlled drug delivery. The biodegradable polymer, poly(ethylene succinate) (PES) polyester, was synthesized with regulated molecular weights for the encapsulation of the Ca2+ channel blocker Nimodipine (NIMO). Increasing the molecular weight of PES enhanced the thermal stability and hydrophobicity of the polyester. The encapsulation of NIMO into PES with increasing molecular weight resulted in the formation of NIMO-loaded PES nanoparticles with improved solubility and stability. The drug release experiments showed that the release of NIMO could be accelerated or prolonged by the molecular weights of PES.