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Evaluation of epithelial transport and oxidative stress protection of nanoengineered curcumin derivative-cyclodextrin formulation for ocular delivery

DOI:10.1007/s12272-019-01154-9 期刊:Archives of Pharmacal Research 出版年份:2019 更新时间:2025-11-21 11:24:58
摘要: 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.
作者: Pooja Maharjan,Meong Cheol Shin,Minki Jin,Daseul Kim,JaeWook Yang,Anjila Maharjan,Kwan Hyung Cho,Man Su Kim,Kyoung Ah Min
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To investigate the changes in drug solubility by forming inclusion complexes with different derivatives of hydroxypropyl (HP)-cyclodextrins (CD) for curcumin and tetrahydrocurcumin (THC), and to evaluate their physicochemical properties, cellular permeability, and anti-oxidant activity for ocular delivery applications.

The encapsulation of curcumin and THC into HP-CDs significantly improved their aqueous solubility, stability, and cellular permeability. THC/CD formulations showed enhanced anti-oxidant activity and oxidative protection in ocular epithelial cells and rabbit corneas without causing tissue colorization, making them promising candidates for ophthalmic applications to treat oxidative stress-related ocular diseases.

The study primarily used in vitro and ex vivo models (cell cultures and rabbit corneas), which may not fully replicate in vivo human ocular conditions. The oxidative stress model relied on H2O2, which might not cover all aspects of oxidative stress in ocular diseases. Long-term stability and in vivo efficacy were not extensively evaluated.

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