title: Novel in situ gel systems based on P123/TPGS mixed micelles and gellan gum for ophthalmic delivery of curcumin.
abstract: Curcumin, a natural polyphenol compound, has been widely reported for diverse pharmacological effects and already been investigated for eye diseases. However, the water-insolubility of curcumin and the inherent penetration barriers in cornea make it difficult for curcumin to enter eye. This work aimed to develop ion-sensitive curcumin-loaded Pluronic P123 (P123)/D-a-tocopheryl polyethylene glycolsuccinate (TPGS) mixed micelle in situ gels (CUR-MM-ISGs) to prolong ocular retention time and improve cornea permeability. Central composite design-response surface methodology was applied for the optimization of curcumin-loaded P123/TPGS mixed micelles (CUR-MMs). Characterization tests showed that CUR-MMs were in spherical shape with small size and low critical micelle concentration. After dispersing the micelles in gellan gum solution (0.2%, w/w) at the ratio of 3:1 and 1:1 (v/v), respectively, CUR-MM-ISGs were formed and presented transparent appearance. Sustained release profile was obtained in vitro for both CUR-MM-ISGs (3:1 or 1:1, v/v). The irritation test proved that CUR-MM-ISGs as ophthalmic formulations were gentle and biocompatible towards ocular tissues. In addition, the ex vivo corneal penetration study indicated that the cumulative drug permeation amount of CUR-MM-ISGs (3:1, v/v) was respectively 1.16-fold and 1.32-fold higher than CUR-MM-ISGs (1:1, v/v) and curcumin solution. It can be concluded from these results that the developed ion-sensitive mixed micelle in situ gel system is a potential ophthalmic delivery carrier for curcumin as a poorly soluble drug.
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Duan
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Du
authors.affiliation: Department of Pharmaceutics, College of Pharmacy, Shandong University, 44 Wenhua Xilu, Jinan 250012, China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D001692:Biological Transport; D003315:Cornea; D003474:Curcumin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers; D065546:Drug Liberation; D005163:Factor Analysis, Statistical; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D007509:Irritants; D007700:Kinetics; D008297:Male; D008823:Micelles; D010316:Particle Size; D010539:Permeability; D011060:Poloxalene / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011135:Polysaccharides, Bacterial / Q000737:chemistry*; D011817:Rabbits; D012967:Sodium Dodecyl Sulfate; D012995:Solubility; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D007509:Irritants; D008823:Micelles; D011135:Polysaccharides, Bacterial; D014867:Water; D014810:Vitamin E; C464484:pluronic block copolymer P123; D012967:Sodium Dodecyl Sulfate; D011092:Polyethylene Glycols; C048288:gellan gum; D011060:Poloxalene; D003474:Curcumin; C014225:tocophersolan
keywords: Corneal penetration; Curcumin; Gellan gum; In situ gel