Functional Polymer Materials, Chair for Advanced Materials Synthesis, Department of Chemistry and Pharmacy and Bavarian Polymer Institute , University of Würzburg , Röntgenring 11 , 97070 Würzburg , Germany.
Biomacromolecules. 2019 Aug 12;20(8):3041-3056. doi: 10.1021/acs.biomac.9b00618. Epub 2019 Jul 18.
Despite decades of research, our understanding of the molecular interactions between drugs and polymers in drug-loaded polymer micelles does not extend much beyond concepts such as "like-dissolves-like" or hydrophilic/hydrophobic. However, polymer-drug compatibility strongly affects formulation properties and therefore the translation of a formulation into the clinics. Specific interactions such as hydrogen-bonding, π-π stacking, or coordination interactions can be utilized to increase drug loading. This is commonly based on trial and error and eventually leads to an optimized drug carrier. Unfortunately, due to the unique characteristics of each drug, the deduction of advanced general concepts remains challenging. Furthermore, the introduction of complex moieties or specifically modified polymers hampers systematic investigations regarding polymer-drug compatibility as well as clinical translation. In this study, we reduced the complexity to isolate the crucial factors determining drug loading. Therefore, the compatibility of 18 different amphiphilic polymers for five different hydrophobic drugs was determined empirically. Subsequently, the obtained specificities were compared to theoretical compatibilities derived from either the Flory-Huggins interaction parameters or the Hansen solubility parameters. In general, the Flory-Huggins interaction parameters were less suited to correctly estimate the experimental drug solubilization compared to the Hansen solubility parameters. The latter were able to correctly predict some trend regarding good and poor solubilizers, yet the overall predictive strength of Hansen solubility parameters is clearly unsatisfactory.
尽管经过了几十年的研究，但我们对于载药聚合物胶束中药物与聚合物之间的分子相互作用的理解，还远远超出了“相似相溶”或亲水/疏水等概念。然而，聚合物-药物相容性强烈影响制剂特性，因此会影响制剂从实验室到临床的转化。可以利用氢键、π-π 堆积或配位相互作用等特定相互作用来提高药物载药量。这通常基于反复试验，最终会得到优化的药物载体。不幸的是，由于每种药物的独特特性，推断出先进的通用概念仍然具有挑战性。此外，复杂基团或特异性修饰聚合物的引入，会阻碍对聚合物-药物相容性以及临床转化的系统研究。在这项研究中，我们降低了复杂性，以分离决定药物载药量的关键因素。因此，我们通过实验确定了 18 种不同两亲聚合物对 5 种不同疏水性药物的相容性。随后，将获得的特异性与源自 Flory-Huggins 相互作用参数或 Hansen 溶解度参数的理论相容性进行了比较。一般来说，与 Hansen 溶解度参数相比，Flory-Huggins 相互作用参数不太适合正确估计实验药物的溶解度。后者能够正确预测一些关于良好和不良溶剂的趋势，但 Hansen 溶解度参数的整体预测强度显然不令人满意。
