Evaluation of muco-adhesive tacrolimus patch on caspase-3 induced apoptosis in oral lichen planus: a randomized clinical trial

Abstract

Background The study compared the clinical effectiveness of topical Tacrolimus (TAC) in patches or gel with Triamcinolone acetonide (TRI) gel for erosive/atrophic oral lichen planus (OLP) and investigated the influence of these therapies on Caspase-3 expression as a marker of apoptosis. Methods Thirty patients were randomly assigned into three equal groups to receive either topical TAC 0.1% patch twice daily, topical TAC 0.1% gel, or topical TRI 0.1% gel four times daily for 8 weeks. Each patient's clinical score (CS), visual analogue scale (VAS), and total atrophic area (TAA) of the marker lesion were measured at baseline, 2, 4, and 8 weeks of treatment, as well as after 4 weeks of treatment free period. Caspase-3 expression and lymphocytic counts (LC) were assessed in pre- and post-treatment biopsied stained sections. Results TAC patch resulted in a higher reduction in CS [− 14.00 (15.54%)] and VAS [− 70.21 (15.82%)] followed by TAC gel then TRI gel within the first two weeks. The reduction in VAS and TAA were significantly higher in TAC groups compared to TRI gel, although the difference between TAC treatment was not significant and this was observed throughout the treatment and follow-up periods. Caspase-3 expression increased in connective tissue in all groups. It decreased significantly within the epithelium in both TAC groups but increased in TRI gel. (LC) were significantly lowered with the TAC patch compared to other groups. The percentage change in Caspase-3 epithelial expression was significantly correlated to the CS, TAA, and LC. Conclusion Both TAC patch and gel significantly decreased pain and lesion size than TRI gel, with a significant reduction in Caspase-3 expression within the epithelium in comparison to the increase seen with TRI gel. The study protocol was registered at www.clinicaltrials.gov (NCT05139667) on 01/12/2021.

What can we learn from treatments of oral lichen planus?

“…A 5-year trial found that Tacrolimus inhibited lesion progression and improved subjective complaints ( Utz et al., 2022 ). Another study found that the tacrolimus group showed increased mesenchyme expression of the apoptosis marker caspase-3, which may indicate impaired T-cell viability and reduce local inflammation, explaining its role in OLP immunology ( Ibrahim et al., 2023 ). However, one of the side effects of tacrolimus is that topical application of tacrolimus can release neuropeptides such as substance P to stimulate sensory neurons and produce a transient burning or painful sensation ( Riano Arguelles et al., 2006 ).…”

A self-stabilized and water-responsive deliverable coenzyme-based polymer binary elastomer adhesive patch for treating oral ulcer

“…These mucodhesive patches successfully extended the residence time of the patch in the oral cavity to 3-10 h based on the improved structural stability and multiple interactions with mucosal tissue, which effectively improved the release efficiency of the therapeutic drugs, cytokines and proteins at the site of mucosal injury. In particular, several studies have shown good therapeutic effects on human volunteers and clinical trials have been carried out, which are very encouraging 19,20 , However, most of these oral mucoadhesive patches often require complex preparation techniques. In addition, they lack intrinsic therapeutic efficacy, and exogenous drugs, cytokines or proteins load will increase the cost of the patch or may cause potential drug toxicity.…”