Cell penetrating peptide TAT-functionalized liposomes for efficient ophthalmic delivery of flurbiprofen: Penetration and its underlying mechanism, retention, anti-inflammation and biocompatibility.
Int J Pharm
; 598: 120405, 2021 Apr 01.
Article
in En
| MEDLINE
| ID: mdl-33647409
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 PGE2, IL-6, and TNF-α 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Flurbiprofen
/
Cell-Penetrating Peptides
Aspects:
Implementation_research
Limits:
Animals
Language:
En
Journal:
Int J Pharm
Year:
2021
Document type:
Article
Country of publication:
Netherlands