Pharmacokinetics of topically applied recombinant human keratinocyte growth factor-2 in alkali-burned and intact rabbit eye
- Exp Eye Res. 2015 Jul;136:93-9. doi: 10.1016/j.exer.2015.05.006.
- 1. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; Department of Ophthalmology, The Affiliated Second Hospital of Wenzhou Medical University, #109 Xueyuan West Road, Wenzhou, 325027, China. Electronic address: [email protected].
- 2. Institute of Transfusion Medicine, Academy of Military Medical Sciences, No. 27 Taiping Road, Haidian District, Beijing, 100850, China. Electronic address: [email protected].
- 3. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: [email protected].
- 4. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: [email protected].
- 5. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: [email protected].
- 6. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China. Electronic address: [email protected].
- 7. The National Engineering Research Center of Genetic Medicine, Ninan University, #206 Kaiyuan Road, Economic and Technical Development Zone, Guangzhou, 510730, China. Electronic address: [email protected].
- 8. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; The Eye Hospital of Wenzhou Medical University, #270 Xueyuan West Road, Wenzhou, 325027, China. Electronic address: [email protected].
- 9. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; The National Engineering Research Center of Genetic Medicine, Ninan University, #206 Kaiyuan Road, Economic and Technical Development Zone, Guangzhou, 510730, China. Electronic address: [email protected].
- 10. Key Laboratory Biotechnology Pharmaceutical Engineering, Wenzhou Medical University, Chashan University Park, Wenzhou, 325035, China; The Eye Hospital of Wenzhou Medical University, #270 Xueyuan West Road, Wenzhou, 325027, China. Electronic address: [email protected].
Keratinocyte growth factor-2 (KGF-2), an effective agent in the development of epithelial tissue and regeneration during corneal wound healing, is a potential therapeutic option to treat the corneal diseases with corneal epithelial defects. However the tissue distribution and pharmacokinetics of KGF-2 have not been explored yet in eye upon topical application. Using (125)I-labeled Recombinant human KGF-2 ((125)I-rhKGF-2), tissue distribution of rhKGF-2 in alkali-burned and control rabbit eyes was studied. Our results revealed that (125)I-rhKGF-2 was distributed to all eye tissues examined. The highest radioactivity level was found in the cornea, followed by iris, sclera, ciliary body, lens, aqueous humor, vitreous body, and serum in a greatest to least order. The levels of (125)I-rhKGF-2 were higher in corneas of alkali-burned eyes than those in control eyes though without statistical significance. Calculated pharmacokinetic parameters of t1/2, Cmax, and Tmax of rhKGF-2 in the rabbit corneas were 3.4 h, 135.2 ng/ml, and 0.5 h, respectively. In iris, lens, aqueous humor, and tear, t1/2, Cmax, and Tmax values were 6.2, 6.5, 5.2, and 2.5 h; 23.2, 4.5, 24.1, and 29,498.9 ng/ml; and 1.0, 0.5, 0.5, and 1.0 h, respectively. Predominant and rapid accumulation of rhKGF-2 in corneas suggests that therapeutic doses of rhKGF-2 could be delivered by topical application for treatment of corneal diseases.
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