Control of Drug Release from Microparticles by Tuning Their Crystalline Textures: A Structure–Activity Study
Control of Drug Release from Microparticles by Tuning Their Crystalline Textures: A Structure–Activity Study
复制标题
DOI：
10.1021/acsapm.1c01254
复制
发表时间：
2021-11
影响因子：
5
通讯作者：
C. Miles;Ashley D. Bernstein;Thomas M. Osborn Popp;N. Murthy;Andrew J. Nieuwkoop;A. Gormley
中科院分区：
文献类型：
--
作者：
C. Miles;Ashley D. Bernstein;Thomas M. Osborn Popp;N. Murthy;Andrew J. Nieuwkoop;A. Gormley
由于影响装置和影响药物释放速率的许多环境和化学因素，预测聚合物微粒的药物释放曲线已被证明具有挑战性。通过测量可以影响药物释放的各种聚合物性质，可以使用预测方法来选择具有特定性质的聚合物，这将导致应用所需的释放曲线。为了说明这一点，使用酪醇衍生的聚（酯-芳基化物）、聚（酰胺）和聚（碳酸酯）的文库来评估物理（结晶度、水可及性、热和疏水性）和化学（聚合物-药物相互作用）聚合物性质对高度结晶药物地塞米松释放的影响，所述药物地塞米松以高重量百分比（wt %）负载在微粒中。核磁共振（NMR）实验表明，聚合物和药物没有化学相互作用，而是作为物理混合物存在，即使在暴露于生理条件下。聚合物结晶度数据显示，微晶尺寸与更快的药物释放强烈相关，这表明较大的微晶降低了地塞米松从颗粒基质中扩散出来的曲折度。在具有和不具有药物的颗粒中观察到的这种相关性用本体聚合物再现，表明来自本体聚合物的结晶度数据可用于预测释放曲线，而不必制备载药颗粒。与结晶度数据一致，代表性制剂的颗粒孔径显示具有较大孔的颗粒导致更快的地塞米松释放。有趣的是，在119天释放研究结束时，热性质（玻璃化转变温度和熔融温度）、聚合物疏水性和分子量保留率未显示出与药物释放的任何相关性。
Predicting drug release profiles from polymer microparticles has proven challenging due to the numerous environmental and chemical factors that affect the device and influence the rate of drug release. By measuring the various polymer properties that can influence drug release, a predictive approach can be used to select polymers with specific properties that will lead to the desired release profile for the application. To illustrate this, a library of tyrosol-derived poly(ester-arylate)s, poly(amide)s, and poly(carbonate)s were used to evaluate the effects of physical (crystallinity, water accessibility, thermal, and hydrophobicity) and chemical (polymer–drug interactions) polymer properties on the release of a highly crystalline drug dexamethasone, which was loaded at a high weight percent (wt %) in microparticles. Nuclear magnetic resonance (NMR) experiments showed that the polymer and drug were not chemically interacting and instead exist as a physical mixture even after exposure to physiological conditions. Polymer crystallinity data revealed that crystallite size was strongly correlated with faster drug release, suggesting that larger crystallites reduce the tortuosity for dexamethasone to diffuse out of the particle matrix. This correlation observed in particles with and without the drug was reproduced with bulk polymers, indicating that crystallinity data from bulk polymers can be used to predict release profiles without having to prepare drug-loaded particles. Consistent with the crystallinity data, particle pore sizes of representative formulations showed that particles with larger pores resulted in faster dexamethasone release. Interestingly, thermal properties (glass transition temperature and melting temperature), polymer hydrophobicity, and molecular weight retention at the end of the 119-day release study did not show any correlation with drug release.