Abstract

Hyaluronic acid (HA) particles with divinyl sulfone (DVS) crosslinking at 10% mole ratio (HA macromolecule repeating units) were prepared and demonstrated as versatile drug carriers with sustainable and long-term release capabilities for cancer drugs, corticosteroid, and antibiotics. Two different methods were chosen in drug loading process; encapsulation for cancer drugs, 5-fluorouracil (5FU), mitomycin C (MMC), and doxorubicin (Dox), and dual drug conjugation for anti-inflammatory glucocorticoid dexamethasone (Dex) and antibiotic ciprofloxacin (Cipro) drugs, respectively. It was demonstrated that HA particles prepared during drug encapsulation were attained smaller sizes with 833 ± 46, 867 ± 50, 728 ± 41 nm for 5FU, MMC, and Dox, respectively. Bare and drug loaded HA particles were shown to be blood compatible with the highest hemolytic ratio of 3.1 ± 0.12% for HA-Dex-Cipro conjugates and fairly good blood clotting index with minimum 71.7 ± 6.0% for MMC encapsulated HA particles. Drug release studies from HA particles indicated that depending on the types of cancer drugs, it is possible to gradually release the drug in long-term up to 300 h in linear fashions with the highest release of 9.34 ± 2.25 mg/g for 5FU. Similarly, drug conjugated HA-Dex-Cipro particles were also showed linear dual drug release up to 100 h at physiological conditions, pH 7.4 and 37.5 °C.

抽象的

制备了摩尔比为10％的二乙烯基砜（DVS）交联的透明质酸（HA）颗粒（HA大分子重复单元），并被证明是具有可持续和长期释放能力的多功能药物载体，可用于癌症药物，皮质类固醇和抗生素。在药物装载过程中选择了两种不同的方法；分别用于抗癌药，5-氟尿嘧啶（5FU），丝裂霉素C（MMC）和阿霉素（Dox）的封装，以及抗炎性糖皮质激素地塞米松（Dex）和抗生素环丙沙星（Cipro）药物的双重药物偶联。结果表明，对于5FU，MMC和Dox，在药物封装过程中制备的HA颗粒尺寸较小，分别为833±46、867±50、728±41 nm。裸露和载药的HA颗粒具有血液相容性，HA-Dex-Cipro结合物的溶血率最高，为3.1±0.12％，血液凝结指数相当好，MMC封装的HA颗粒的最低溶血率为71.7±6.0％。HA颗粒的药物释放研究表明，取决于抗癌药物的类型，可以在长达300小时的线性方式下逐步释放该药物，其中5FU的最高释放量为9.34±2.25 mg / g。同样，在生理条件，pH 7.4和37.5°C下长达100小时，药物共轭的HA-Dex-Cipro颗粒也显示出线性双重药物释放。HA颗粒的药物释放研究表明，取决于抗癌药物的类型，可以在长达300小时的线性方式下逐步释放该药物，其中5FU的最高释放量为9.34±2.25 mg / g。同样，在生理条件，pH 7.4和37.5°C下长达100小时，药物共轭的HA-Dex-Cipro颗粒也显示出线性双重药物释放。HA颗粒的药物释放研究表明，取决于抗癌药物的类型，可以在长达300小时的线性方式下逐步释放该药物，其中5FU的最高释放量为9.34±2.25 mg / g。同样，在生理条件，pH 7.4和37.5°C下长达100小时，药物共轭的HA-Dex-Cipro颗粒也显示出线性双重药物释放。