Topical Delivery of Levocarnitine to the Cornea and Anterior Eye by Thermosensitive in-situ Gel for Dry Eye Disease

Abstract

Purpose To prepare the levocarnitine thermosensitive in situ gel (LCTG) and evaluate its effect on dry eye disease (DED). Methods Draize eye irritation test and other examinations were used to evaluate the eye irritation after multiple administration of LCTG. The Schirmer test, fluorescein sodium staining, HE staining and TUNEL staining were used to detect the tear secretion, corneal injury, histopathological changes of the cornea and lacrimal gland, and the apoptosis rate of cornea epithelial cells after 3 days of the administration. The conjunctival goblet cell density was detected by PAS staining, and the expression levels of matrix metalloproteinase-3 (MMP-3) and matrix metalloproteinase-9 (MMP-9) of corneal epithelial cells were detected by immunofluorescence staining after 7 days of the administration. Results LCTG is non-irritating to rabbit eyes and has good biocompatibility. LCTG administration for 3 days can significantly increase the amount of tear secretion in mice with DED, promote corneal epithelial integrity and central corneal epithelium thickness recovery, and improve the pathological morphology and structure of corneal and lacrimal gland tissues, and reduce the apoptosis rate of the corneal epithelial cells. After 7 days of the administration, the preparation can promote the proliferation of conjunctival goblet cells and down-regulate the cornea expression levels of MMP-3 and MMP-9 in epithelial cells. Conclusion The LCTG has a good curative effect on mice with DED, and the overall curative effect is better than that of levocarnitine solution.

Nanoceria-Mediated Cyclosporin A Delivery for Dry Eye Disease Management through Modulating Immune–Epithelial Crosstalk

“…Monotherapy of P/CeO 2 could also increase mice TBUT, while CsA showed trivial improvement of TBUT (from 2.17 ± 0.75 to 3.50 ± 1.52 s). We next performed the Schirmer test, 47 which directly indicated the tear secretion amount (Figure 4h,i). In the 15 s Schirmer test, P/CeO 2 (from 2.30 ± 0.84 to 5.20 ± 0.76 mm) and CsA (from 2.80 ± 0.76 to 4.50 ± 0.94 mm) showed partial efficiency, while Cs@P/CeO 2 administration significantly improved DED mice tear secretion (from 2.83 ± 0.52 mm to a healthy level of 7.08 ± 2.29 mm).…”

A promising ‘single’ and ‘dual’ drug-nanocomposite enriched contact lens for the management of glaucoma in response to the tear fluid enzyme

“…In brief, 1% sodium fluorescence dye (w/v) solution (50 mL) was dropped into the lower eyelid conjunctival sac of the rabbits. Then the cobalt blue light of a slit lamp microscope was used to observe whether the corneal epithelium showed positive staining after 60 s. 22,23…”

“…10) similar to the earlier studies. 22,23 Therefore, the developed contact lens was found to be suitable for ocular administration.…”

Design of an L-Valine-Modified Nanomicelle-Based Drug Delivery System for Overcoming Ocular Surface Barriers

“…The medication was delivered four times per day, with 4 h between treatments for 7 days. A Draize test was carried out with a slit lamp microscope to observe the rabbit's ocular surface each day and at 1, 2, 4, 24, 48 and 72 h after the last treatment administration to record the ocular conditions, as shown in Tables S1 and S2 [30]. Corneal staining with fluorescein sodium (FLS) was observed under the cobalt blue light of a slit lamp microscope after each Draize test.…”