Clinical and biochemical assessment of the effect of topical use of coenzyme Q10 versus topical corticosteroid in management of symptomatic oral lichen planus: randomized controlled clinical trial.

BACKGROUND: Oral lichen planus (OLP) is a chronic mucocutaneous immunologically mediated condition that has a great adverse effect on oral functions. Corticosteroids are still the first drugs of choice used in the treatment of OLP; however, they have extensive medical side effects. The present study was carried out to assess the clinical therapeutic effect of the topical use of coenzyme Q10 (coQ10 or ubiquinol) versus topical corticosteroids in the management of symptomatic OLP and to determine whether the effect, if any, was due to the powerful antioxidant activity of coQ10. SUBJECTS AND METHODS: We performed a randomized, double blinded controlled trial at the Faculty of Dentistry, Cairo University, Egypt. The study was conducted on 34 patients suffering from symptomatic OLP. Patients were randomly divided into two groups: intervention group (I),who received topical CoQ10 in the form of mucoadhesive tablets (40% CoQ10) 3 times daily for one month and control group (II),who received topical corticosteroid (kenacort in Orabase: triamcinolone acetonide 0.1% 5-g adhesive paste - dermapharm), 4 times daily for one month. Patients were evaluated at one-week intervals using the clinical parameters (score) of pain (VAS) and lesion size. Additionally, salivary levels of malondialdehyde (MDA) were detected in both groups before and after treatment using ELISA. All recorded data were analysed using independent t test, ANOVA followed by Bonferroni post hoc test for lesion size and salivary level of MDA data and Mann-Whitney U test and Friedman test for VAS data. RESULTS: Both groups showed a significant reduction in pain and the size of the lesions (p ≤ 0.05) with no statistically significant difference between them (p > 0.05), and this clinical improvement was associated with a reduction in the salivary levels of MDA in both groups. CONCLUSIONS: The topical use of CoQ10 mucoadhesive tablets was as effective as the topical use of triamcinolone acetonide, and its clinical effect was associated with a reduction in the salivary level of MDA. TRIAL REGISTRATION: The study protocol was registered at www. CLINICALTRIAL: gov (NCT04091698) and registration date: 17/9/2019.

Investigation of the Potential of Nebivolol Hydrochloride-Loaded Chitosomal Systems for Tissue Regeneration: In Vitro Characterization and In Vivo Assessment.

In this study, we evaluated the synergistic effect of nebivolol hydrochloride (NVH), a third-generation beta-blocker and NO donor drug, and chitosan on the tissue regeneration. Ionic gelation method was selected for the preparation of NVH-loaded chitosomes using chitosan lactate and sodium tripolyphosphate. The effect of different formulation variables was studied using a full factorial design, and NVH entrapment efficiency percentages and particle size were selected as the responses. The chosen system demonstrated high entrapment efficiency (73.68 ± 3.61%), small particle size (404.05 ± 11.2 nm), and good zeta potential value (35.6 ± 0.25 mV). The best-achieved formula demonstrated spherical morphology in transmission electron microscopy and amorphization of the crystalline drug in differential scanning calorimetry and X-ray diffraction. Cell culture studies revealed a significantly higher proliferation of the fibroblasts in comparison with the drug suspensions and the blank formula. An in vivo study was conducted to compare the efficacy of the proposed formula on wound healing. The histopathological examination showed the superiority of NVH-loaded chitosomes on the wound proliferation and the non-significant difference in the collagen deposition after 15 days of the injury to that of intact skin. In conclusion, NVH-loaded chitosomes exhibited promising results in enhancing skin healing and tissue regeneration.

Development and Optimization of Terpene-Enriched Vesicles (Terpesomes) for Effective Ocular Delivery of Fenticonazole Nitrate: In vitro Characterization and in vivo Assessment.

OBJECTIVE: The aim of the current study was to load fenticonazole nitrate, a slightly water-soluble antifungal agent, into terpene-enriched phospholipid vesicles (terpesomes) as a potential delivery system for the management of ocular fungal infection. METHODS: Thin film hydration method was used to prepare terpesomes according to a 32 full factorial design to inspect the effect of several variables on vesicles' features. The investigated factors were terpenes type (X1) and terpenes amount (X2) while the dependent responses were encapsulation efficiency percent (Y1), particle size (Y2) and polydispersity index (Y3). Design Expert® program was used to chose the best achieved formula. The selected terpesomes were further optimized via incorporation of a positive charge inducer (stearylamine) to enhance adhesion to the negatively charged mucus covering the eye surface. The in vivo performance of the optimized fenticonazole nitrate-loaded terpesomes relative to drug suspension was evaluated by measuring the antifungal activity (against Candida albicans) retained in the tear's fluid at different time intervals after ocular application in albino rabbits. RESULTS: The optimized terpesomes showed spherical vesicles with entrapment efficiency of 79.02±2.35%, particle size of 287.25±9.55 nm, polydispersity index of 0.46±0.01 and zeta potential of 36.15±1.06 mV. The in vivo study demonstrated significantly higher ocular retention of the optimized fenticonazole nitrate-loaded terpesomes relative to the drug suspension. Moreover, the histopathological studies proved the safety and biocompatibility of the prepared terpesomes. CONCLUSION: The obtained results verified the potential of the terpesomes for safe and effective ocular delivery of fenticonazole nitrate.

Utilization of PEGylated cerosomes for effective topical delivery of fenticonazole nitrate: in-vitro characterization, statistical optimization, and in-vivo assessment.

In this investigation, we focused on ceramide IIIB, a skin component whose depletion tends to augment multiple skin disorders and fungal infections. Ceramide IIIB was included into PEGylated surfactant-based vesicular phospholipid system to formulate 'PEGylated cerosomes' (PCs) loaded with fenticonazole nitrate (FTN). FTN is a potent antifungal agent adopted in the treatment of mixed mycotic and bacterial infections. The ceramide content of the vesicles may provide protective and regenerative skin activity whereas Brij®; the PEGylated surfactant, can enhance drug deposition and skin hydration. Both components are expected to augment the topical effect of FTN. PCs were prepared by thin-film hydration technique. A 23 full-factorial design was applied to study the effect of ceramide amount (X1), Brij type (X2) and Brij amount (X3) on the physicochemical properties of the formulated PCs namely; entrapment efficiency (EE%;Y1), particle size (PS;Y2), polydispersity index (PDI;Y3) and zeta potential (ZP;Y4). The optimal formula was selected for further in-vivo dermatokinetic and histopathological study. The optimal FTN-loaded PC (PC6) showed nanosized cerosomes (551.60 nm) with high EE% (83.00%w/w), and an acceptable ZP value of 20.90 mV. Transmission electron micrographs of the optimal formula illustrated intertwined tubulation form deviated from the conventional spherical vesicles. Finally, the dermatokinetic study of PC6 showed higher drug concentration and localization of FTN in skin layers when compared with FTN suspension and the histopathological study confirmed its safety for topical application. The overall findings of our study verified the effectiveness of utilizing PEGylated cerosomes to augment the activity of FTN as a topical antifungal agent.

Preparation of novel phospholipid-based sonocomplexes for improved intestinal permeability of rosuvastatin: In vitro characterization, dynamic simulation, Caco-2 cell line permeation and in vivo assessment studies.

The study aimed to fabricate innovative drug-phospholipid complexes termed "sonocomplexes" adopting ultrasound irradiation to increase the liposolubility and to enhance the intestinal absorption of rosuvastatin as a model drug for BCS class III active pharmaceutical ingredients (APIs). A 22 full factorial design was fashioned to investigate the influence of phosphatidylcholine content in the phospholipid (∼30 and 60%) and molar ratio of phospholipid to rosuvastatin (1:1 and 2:1) on physicochemical properties of sonocomplexes. In comparison to pure drug, sonocomplexes showed a minimum of about 2 folds and a maximum of about 15 folds increase in lipophilicity (expressed in terms of partition coefficient, P). Results of molecular docking, dynamic simulations, Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) confirmed the strong interactions between rosuvastatin and the phospholipid via hydrogen bonding interaction, van der Waals forces and hydrophobic interaction. The complexation efficiency reached around 99% and transmission electron microscopy (TEM) of the aqueous dispersion of the optimal sonocomplex showed spherical nanosized vesicles. The optimal sonocomplex showed significantly superior Caco-2 cells permeability and markedly better oral bioavailability compared to the pure drug. In summary, sonocomplexes can be considered as effective approach for enhancing the liposolubility and consequently the intestinal permeability of BCS class III drugs.

Nano-transfersomal ciprofloxacin loaded vesicles for non-invasive trans-tympanic ototopical delivery: in-vitro optimization, ex-vivo permeation studies, and in-vivo assessment.

Ciprofloxacin is a synthetic fluoroquinolone antibiotic that has been used for systemic treatment of otitis media in adults. It was approved for topical treatment of otorrhea in children with tympanostomy tubes. The aim of this work was to enhance the local non-invasive delivery of ciprofloxacin to the middle ear across an intact tympanic membrane (TM) in an attempt to treat acute otitis media (AOM) ototopically. In order to achieve this goal, ciprofloxacin nano-transfersomal vesicles were prepared by thin film hydration (TFH) technique, using several edge activators (EAs) of varying hydrophilic-lipophilic balance (HLB) values. A full factorial design was employed for the optimization of formulation variables using Design-Expert(®) software. The optimal formulation was subjected to stability testing, ex-vivo permeation studies (through ear skin and TM of rabbits), and in-vivo evaluation. Results revealed that the optimal formulation (composed of phospholipid and sodium cholate as an EA at a molar ratio of 5:1) exhibited enhanced ex-vivo drug flux through ear skin and TM when compared with the commercial product (Ciprocin(®) drops). It demonstrated a greater extent of in-vivo drug deposition in the TM of albino rabbits relative to Ciprocin(®). Consequently, transfersomes could be promising for the non-invasive trans-tympanic delivery of ciprofloxacin.