title: Intranasal delivery of nanomicelle curcumin promotes corneal epithelial wound healing in streptozotocin-induced diabetic mice.
abstract: Corneal nerves are mainly derived from the ophthalmic branch of the trigeminal ganglion (TG). Corneal neuropathy contributes to epithelial degenerative changes in diabetic keratopathy. Efficient drug delivery to TG may be beneficial for the treatment of diabetic keratopathy. This article described intranasal delivery of nanomicelle curcumin to correct pathophysiological conditions in TG to promote corneal epithelial/nerve wound healing in streptozotocin-induced diabetic mice. A diabetic mice model with corneal epithelium abrasion was established. Ocular topical and/or intranasal nanomicelle curcumin treatments were performed, and treatment efficacy and mechanisms of action were explored. Results showed that intranasal nanomicelle curcumin treatment promoted corneal epithelial wound healing and recovery of corneal sensation. Enhanced accumulation of reactive oxygen species, reduced free radical scavengers, increased mRNA expressions of inflammatory cytokines, and decreased mRNA expressions of neurotrophic factors in the cornea and TG neuron were observed in diabetic mice with corneal epithelium abrasions. Intranasal nanomicelle curcumin treatment effectively recovered these pathophysiological conditions, especially that of the TG neuron, and a strengthened recovery was observed with ocular topical combined with intranasal treatment. These findings indicated that intranasal curcumin treatment effectively helped promote diabetic corneal epithelial/nerve wound healing. This novel treatment might be a promising strengthened therapy for diabetic keratopathy.
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.
authors.forename: Chuanlong
authors.initials: C
authors.lastname: Guo
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.|School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan 250022, China.
authors.forename: Mengshuang
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Qi
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.|School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan 250022, China.
authors.forename: Guiming
authors.initials: G
authors.lastname: Lin
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Cui
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.
authors.forename: Fengjie
authors.initials: F
authors.lastname: Li
authors.affiliation: State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong Academy of Medical Sciences, Qingdao 266071, China.|School of Medicine and Life Sciences, Shandong Academy of Medical Sciences, University of Jinan, Jinan 250022, China.
authors.forename: Xianggen
authors.initials: X
authors.lastname: Wu
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D003316:Corneal Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003474:Curcumin / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019573:Epithelium, Corneal / Q000293:injuries* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008823:Micelles; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D008823:Micelles; D003474:Curcumin