A Biodegradable, Sustained-Released, Tacrolimus Microfilm Drug Delivery System for the Management of Allergic Conjunctivitis in a Mouse Model

Abstract

PURPOSE. To investigate the drug release profiles of a tacrolimus-loaded poly(D,L-lactide-co-ecaprolactone) (PLC) microfilm, and to evaluate its efficacy on the treatment of allergic conjunctivitis using a mouse model. METHODS.The in vitro and in vivo drug release profiles were first characterized. Balb/c mice were immunized with short ragweed (SRW) injection followed by re-challenges with topical SRW solution. The mice were divided into six groups (n ¼ 12 in each): negative control (NC); positive control (PC); tacrolimus eye drops (Te); subconjunctival tacrolimus microfilm (Tm); dexamethasone eye drops (De); and tacrolimus þ dexamethasone eye drops (TeþDe). The mice were evaluated for 28 days by a scoring system for allergic conjunctivitis. Histopathologic and immunohistochemical staining with CD11c, CD4, and IL-4 were performed.RESULTS. The microfilms were biocompatible and delivered clinically sufficient dose in a sustained manner, with a steady rate of 0.212 to 0.243 lg/day in vivo. Compared to the PC groups, the Te, Tm, De, and TeþDe groups significantly reduced the allergic clinical scores throughout the study period (all P < 0.01; 0.0 6 0.0, 5.6 6 0.9, 3.3 6 0.9, 3.2 6 0.9, 1.9 6 0.4 and 1.7 6 0.8 for the NC, PC, Tm, Te, De, and TeþDe groups, respectively, at 4 weeks after treatment). The suppressed eosinophils, CD11c, CD4, and IL-4 expression were also observed in all treatment groups, with more reduction in the TeþDe group.CONCLUSIONS. Tacrolimus-loaded microfilms display good biocompatibility and desirable sustained drug release. It was as effective as conventional tacrolimus eye drops on the treatment of allergic conjunctivitis, providing a promising clinically applicable alternative for controlling allergic disease activity, or other immune-mediated ocular diseases.

Therapeutic efficacy of tacrolimus in vernal keratoconjunctivitis: a meta-analysis of randomised controlled trials

“…19 Several studies have shown that TAC plays an important role in the treatment of chronic allergic conjunctivitis, based on TAC's effect in substantially reducing the symptom score by approximately 50%. [20][21][22][23][24][25][26] In addition, the safety of long-term TAC application in the treatment of allergic conjunctivitis has also been verified. A study by Al-Amri et al, 27 using 0.1% topically applied TAC for treatment of AKC over 48 months, demonstrated the control and remission of the disease in the absence of other medications.…”

Nanotechnology for the Treatment of Allergic Conjunctival Diseases

“…Immunomodulators, such as cyclosporin A and tacrolimus, suppress T-helper cell-mediated response, B-cell proliferation, and prostaglandin and cytokine release, especially interleukin (IL)-2, IL-4, and IL-5, which play roles in ocular allergic diseases [16]. It also blocks the release of histamine from mast cells.…”

“…Nanomedicine therefore becomes a potential alternative solution to deliver these drugs. As allergic conjunctival diseases are chronic and recurrent conditions, long-term use of topical eye drops and good patient compliance are necessary [16]. However, topical eye drops have a poor bioavailability of less than 10% and a short duration of action and therefore frequent application is required to achieve a therapeutic level [23,24].…”

Tissue Responses and Wound Healing following Laser Scleral Microporation for Presbyopia Therapy

“…All the quantification was performed on three randomly selected sections for each sample at 100× magnification by a single masked observer (ETWP). 23,24…”