College of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, 197 Injero, Gimhae, Gyeongnam, 50834, Republic of Korea.
Department of Ophthalmology, College of Medicine, Inje University, 75 Bokjiro, Busanjin-gu, Busan, 47392, Republic of Korea.
Arch Pharm Res. 2019 Oct;42(10):909-925. doi: 10.1007/s12272-019-01154-9. Epub 2019 Apr 27.
Ocular drug delivery has been a well-known route for the drug administration for the treatment of ocular diseases. However, numerous anatomical and physiological barriers prevailing in the eye itself create considerable challenges for achieving the necessitated therapeutic efficacy along with ocular bioavailability. However, recent advances in nanoengineered strategies hold definite promises in terms of devising improved ophthalmic medicines for the effective drug delivery to target the sites with enhanced ocular bioavailability. Curcumin, a hydrophobic polyphenol yellow colored compound, and its metabolic reduced product, tetrahydrocurcumin (THC), have been known for their beneficial pharmacological functions, such as anti-inflammatory or anti-oxidant activities at various tissue sites. However, the low aqueous solubility of these compounds results in their poor bioavailability, thereby limiting their widespread application. Therefore, in the present study, we investigated the changes in drug solubility by forming inclusion complexes with different derivatives of hydroxypropyl (HP)-cyclodextrins (CD). To this end, the spray drying technique was used for nanoengineering curcumin or THC-loaded formulations to improve the stability of formulations during the storage. The formulations were characterized in terms of physicochemical properties and cellular permeability. The results demonstrated that the encapsulation of curcumin (or THC) into the HP-CDs significantly increased the drug solubility and enhanced the corneal and retinal epithelial permeability. Curcumin or THC complexes in HP-CDs with improved bioavailability also induced anti-oxidant activity (SOD1, CAT1, and HMOX1) in higher levels in the ocular epithelial cells and showed oxidative protection effects in rabbit cornea tissues that will boost up their application in ocular medicine.
眼部给药一直是治疗眼部疾病的药物给药的熟知途径。然而，眼睛本身存在的许多解剖学和生理学屏障给实现必要的治疗效果和眼部生物利用度带来了相当大的挑战。然而，纳米工程策略的最新进展在设计改进的眼科药物方面具有明确的前景，以实现有效药物递送到目标部位，提高眼部生物利用度。姜黄素是一种疏水性多酚黄色化合物，其代谢还原产物四氢姜黄素（THC）具有抗炎或抗氧化等有益的药理作用，在各种组织部位均有活性。然而，这些化合物的低水溶性导致其生物利用度差，从而限制了它们的广泛应用。因此，在本研究中，我们通过与不同羟丙基（HP）-环糊精（CD）衍生物形成包合物来研究药物溶解度的变化。为此，我们采用喷雾干燥技术对姜黄素或 THC 负载制剂进行纳米工程化，以提高制剂在储存过程中的稳定性。我们从物理化学性质和细胞通透性方面对制剂进行了表征。结果表明，姜黄素（或 THC）包封到 HP-CDs 中显著提高了药物溶解度，并增强了角膜和视网膜上皮细胞的通透性。具有改善生物利用度的 HP-CDs 中的姜黄素或 THC 复合物还能在眼部上皮细胞中诱导更高水平的抗氧化活性（SOD1、CAT1 和 HMOX1），并在兔眼角膜组织中显示出氧化保护作用，这将促进它们在眼科药物中的应用。
