title: Pimecrolimus micelle exhibits excellent therapeutic effect for Keratoconjunctivitis Sicca.
abstract: Poor corneal penetration and short residence time on the ocular surface are two major bottlenecks for conventional ophthalmic formulations. To overcome the foregoing dilemmas, we prepared two novel formulations of pimecrolimus nanomicelles (PNM) with particle size of 37.85 ± 1.21 nm and thermosensitive hydrogel (PTH) for treating Keratoconjunctivitis Sicca (KCS). PNM were investigated by transmission electron microscopy (TEM), Malvern laser particle size analyzer, X-ray diffraction (XRD) system, and the content of drug in PNM was measured by high-performance liquid chromatography (HPLC). The drug loading and encapsulation efficiency reached to 7.57% ± 0.10% and 97.9% ± 1.26%, respectively. PTH displayed special gel-sol transition behavior with temperature increasing from 4 °C to 37 °C. The in vitro release profile demonstrated that PNM and PTH exhibited sustained-release behavior compared with free pimecrolimus oil-based eye drop (FPO). In addition, we established a mouse model of KCS induced by benzalkonium chloride to evaluate the therapeutic outcome of different pimecrolimus formulations. The production of tear, fluorescein staining scores and histopathologic examinations of the cornea were assessed in detail. The results confirmed that PNM had the best therapeutic effect among all formulations based on its higher drug encapsulation capability, favourable permeability and sustained release. All these indicated that PNM could serve as a potent ophthalmologic agent for KCS.
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yingfang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. Electronic address: cheng13980029671@163.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
authors.forename: Xuelian
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacy, Shandong Provincial Qian Foshan Hospital, Jinan 250014, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Key Laboratory of Marine Drugs, Chinese Ministry of Education, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China. Electronic address: lvzhihua@ouc.edu.cn.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Lv
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D065546:Drug Liberation; D007638:Keratoconjunctivitis Sicca / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D044367:Phase Transition; D016559:Tacrolimus / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D044366:Transition Temperature; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D008823:Micelles; C117268:pimecrolimus; D016559:Tacrolimus
keywords: Hydrogel; Keratoconjunctivitis Sicca; Micelles; Pimecrolimus