4.7 Article

Cell penetrating peptide TAT-functionalized liposomes for efficient ophthalmic delivery of flurbiprofen: Penetration and its underlying mechanism, retention, anti-inflammation and biocompatibility

期刊

出版社

ELSEVIER
DOI: 10.1016/j.ijpharm.2021.120405

关键词

Cell penetrating peptide; TAT; Ophthalmic delivery; Liposomes

资金

  1. National Natural Science Foundation of China [81703717]
  2. Shandong Province `Taishan Scholar' Project [ts201712067, tsqn201909143]
  3. Shandong Provincial Natural Science Foundation [ZR2014HQ069]
  4. Project of Shandong Province Higher Educational Science and Technology Program [J14LM51]
  5. Research Foundation of Shandong Educational Committee [2019KJK014]

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This study successfully designed a TAT-Lip system that can promote corneal drug delivery, and its effectiveness was confirmed through in vitro and in vivo experiments, effectively reducing drug loss rate and demonstrating good anti-inflammatory effects in animal models.
In treating eye diseases, topical administration on the ocular surface is the most convenient and acceptable route. However, the intraocular efficiency of non-invasive drug delivery systems is still considerably hampered by the eye's defense barriers. In this work, cell-penetrating peptide TAT-functionalized, flurbiprofen-loaded liposomes (TAT-FB-Lip) were designed to enable transcorneal drug delivery and prolong ocular surface retention. The corneal penetration-promoting properties of TAT-functionalized liposomes (TAT-Lip) were confirmed in vitro using a corneal permeability assay and the HCE-T cell sphere model and in vivo by aqueous humor pharmacokinetics assessment. TAT-Lip induced an increase in intracellular calcium ion concentration and membrane potential depolarization. F-actin images of HCE-T cells treated with TAT-Lip show the tight junctions between cells partly opened. The cellular internalization pathway mainly depended on the electrostatic interaction between TAT-Lip and the cell membrane, and there is a certain degree of energy dependence. The pharmacokinetics of flurbiprofen in tears demonstrated TAT-Lip could reduce the drug loss rate. Moreover, the anti-inflammatory effect of TAT-FB-Lip was enhanced by markedly suppressing PGE(2), IL-6, and TNF-alpha production in tears and aqueous humor in a rabbit conjunctivitis model. In conclusion, this work demonstrates that TAT-Lip is an effective ocular drug carrier system that facilitates transcorneal delivery.

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