title: Gelucire44/14 as a novel absorption enhancer for drugs with different hydrophilicities: in vitro and in vivo improvement on transcorneal permeation.
abstract: The objective of this study was to investigate the application of Gelucire44/14 as a novel absorption enhancer in ophthalmic drug delivery system. Six compounds, namely ribavirin, puerarin, mangiferin, berberin hydrochloride, baicalin, and curcumin in the order of increasing lipophilicity were selected as model drugs. The effect of Gelucire44/14 on transcorneal permeation was evaluated across excised rabbit cornea. Ocular irritation and precorneal retention time were assessed. Additionally, aqueous humor pharmacokinetic test was performed by microdialysis. The results indicated that Gelucire44/14, at a concentration of 0.05% or 0.1% (w/v), was found to maximally increase the apparent permeability coefficient by 6.47-, 4.14-, 3.50-, 3.97-, 2.92-, and 1.86-fold for ribavirin, puerarin, mangiferin, berberin hydrochloride, baicalin, and curcumin, respectively (p < 0.05). Moreover, Gelucire44/14 was nonirritant at broad concentrations of 0.025%-0.4% (w/v). Pharmacokinetic tests showed that Gelucire44/14 promoted ocular bioavailability of the compounds as indicated by 5.40-, 4.03-, 3.46-, 3.57-, 2.77-, and 1.77-fold maximal increase in the area under the curve for the drugs aforementioned, respectively (p < 0.01). Therefore, Gelucire44/14 exerted a significant improvement on the permeation of both hydrophilic and lipophilic compounds, especially hydrophilic ones. Hence, Gelucire44/14 can be considered as a safe and effective absorption enhancer for ophthalmic drug delivery system.
authors.affiliation: Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin 300193, PR China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, PR China.
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.affiliation: Engineering Research Center of Modern Chinese Medicine Discovery and Preparation Technique, Ministry of Education, Tianjin 300193, PR China; Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, PR China. Electronic address: lonerliuzd@163.com.
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Engineering Center of Tianjin Zhongxin Pharmaceutical Group Corporation Ltd., Tianjin 300193, PR China.
authors.forename: Chengui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin 300193, PR China.
authors.forename: Boli
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000042:Absorption; D000277:Adjuvants, Pharmaceutic / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D001082:Aqueous Humor / Q000378:metabolism; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D016503:Drug Delivery Systems; D057927:Hydrophobic and Hydrophilic Interactions; D007322:Instillation, Drug; D017551:Microdialysis; D010539:Permeability; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000633:toxicity; D011817:Rabbits; D012995:Solubility; D013997:Time Factors
chemical_list: D000277:Adjuvants, Pharmaceutic; D004364:Pharmaceutical Preparations; C104509:gelucire 44-14; D011092:Polyethylene Glycols