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.
Department of Physical Chemistry and Materials Science, University of Szeged, H-6720, Rerrich Béla tér 1, Szeged, Hungary.
Int J Pharm. 2022 Apr 25;618:121653. doi: 10.1016/j.ijpharm.2022.121653. Epub 2022 Mar 9.
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, 4.3-5.05 kDa) through the polymerization time (40-80 min) increased the thermal stability (T= ∼61-80 °C) and slightly the hydrophobicity (Θ= ∼27-41°) of the obtained aliphatic polyester. Next, this biodegradable polymer was used for the encapsulation of Ca 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 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 (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.
在本研究中，我们证明了众所周知的聚合物分子量依赖性溶解度性质也可以在控制药物释放领域中得到应用。为了证明这一点，通过在 185°C 下以等摩尔比的乙二醇和琥珀酸单体无催化剂直接聚合，合成了具有聚合时间调节分子量的聚(琥珀酸丁二醇酯) (PES)聚酯。DSC 和接触角测量表明，通过聚合时间（40-80 分钟）增加分子量（M，4.3-5.05 kDa）会增加热稳定性（T=∼61-80°C）并略微增加所得脂肪族聚酯的疏水性（Θ=∼27-41°）。接下来，将这种可生物降解的聚合物用于封装钙通道阻滞剂尼莫地平（NIMO），以克服其较差的水溶性并提高药物的生物利用度。通过溶解度（δ）和 Flory-Huggins 相互作用（混溶性）参数（χ）证明了药物/聚合物的相容性。随着 M 的增加，NIMO 纳米沉淀包封在 PES 中形成了 270±103nm 的载有 NIMO 的 PES 纳米颗粒（NPs）。此外，基于 XRD 测量，封装的 NIMO 载 PES NPs 显示出较低的药物结晶度，不仅提高了 NIMO 在水介质中的水溶性，甚至提高了其水稳定性。体外药物释放实验表明，NIMO 药物的释放可以通过 PES 的分子量来加速甚至延长。由于 PES 聚酯的低结晶度和包封的 NIMO 药物的小粒径导致具有较低分子量（4.3 kDa 和 4.5 kDa）的 PES 中的 NIMO 溶解度和释放过程增强，与纯结晶 NIMO 相比。然而，进一步增加分子量（5.05 kDa）已经减少了药物释放量，从而提供了延长的治疗效果并提高了 NIMO 药物的生物利用度。
