A comparative physicochemical and pharmacological evaluation of dexamethasone sodium phosphate and betamethasone sodium phosphate mucoadhesive gels for the treatment of oral submucous fibrosis in rats

Abstract The present study is aimed to formulate steroidal oral mucoadhesive gels of dexamethasone sodium phosphate and betamethasone sodium phosphate. Six gel formulations each of dexamethasone sodium phosphate and betamethasone sodium phosphate prepared using two different polymers carboxymethyl cellulose sodium and hydroxypropyl methylcellulose, in variable proportions. All the formulations subjected for assessment of various physicochemical parameters and mechanical properties. The formulations BSP5 and DSP5, both containing 1.25 % carboxymethyl cellulose sodium, 1.25 % hydroxypropyl methylcellulose, exhibiting mucoadhesive strength of 12.300 ± 0.004 and 12.600 ± 0.01, adhesiveness of 28.04 ± 00 and 30.02 ± 00, cohesiveness of 28.04 ± 00 and 30.02 ± 00, drug release of 86.869 ± 0.380 % and 88.473 ± 0.457 % respectively were considered as promising ones and were further subjected for stability studies and in vivo study in male albino rats. Formulation DSP5 upon oral application for 4 months in arecoline induced oral submucous fibrosis rats, showed more than 80 % reduction in fibrosis as compared with BSP5 which showed nearly 50 % reduction. These results were concluded on the basis of histopathological profile and weight gain among the experimental animals during in vivo study. Hence, DSP5 by minimizing the painful injuries and morbidities justifies being suitable noninvasive model for OSMF treatment.

Efficacy of curcumin in the treatment of oral submucous fibrosis: a Meta-analysis / 华西口腔医学杂志

OBJECTIVES@#This study was performed to review the efficacy of curcumin in the treatment of oral submucous fibrosis systematically.@*METHODS@#We searched seven databases, including Web of Science, PubMed, EBSCO, The Cochrane Library, CNKI, WanFang Data, and VIP, to obtain randomized controlled trials related to the treatment of oral submucous fibrosis by curcumin. Each database was searched from inception to 30 June 2019. RevMan 5.3 software was used for the meta-analysis.@*RESULTS@#Six randomized controlled trials involving 350 patients were included in this study. Meta-analysis showed that curcumin can increase the maximal mouth opening and improve burning sensation compared with placebo treatment. Curcumin was not as effective as the controls in achieving maximal mouth opening after 1 month of treatment. However, no statistically significant difference was observed between the treatments from 2 months to 6 months. Curcumin significantly improved burning sensation compared with the controls after 3 months of treatment. No statistically significant diffe-rence in burning sensation was observed between the curcumin and control groups after 1, 2, and 6 months of treatment.@*CONCLUSIONS@#The current evidence shows that curcumin is an effective treatment for improving maximal mouth opening and burning sensation in patients with oral submucous fibrosis. Given the limited number and low quality of the included studies, however, more high-quality studies are needed to verify these findings.

Effectiveness of Pentoxifylline in the treatment of oral submucous fibrosis patients: a case-control study

Background: Oral submucous fibrosis (OSMF) is a potentially malignant disorder largely seen in the South-Asian countries where areca nut is found to be the main predisposing factor. Pentoxifylline, a methylxanthine derivative, has vasodilating properties and is believed to increase the vascularity of the mucosal layer. This study was designed to determine the effect of pentoxifylline (Trental) on the clinical progression of oral submucous fibrosis. Aim: The present study was aimed to evaluate the effectiveness of drug pentoxifylline in the management of OSMF and to correlate the clinical parameters evaluated before and after treatment. Methods: Study Design: This investigation was conducted as a case-control study incorporating a Control Group in comparison to a Study Group where pentoxifylline 400 mg was administered 3 times daily, as coated, sustainedrelease tablets for prescribed for 3 months. The stipulated period for the study was 8 months and a total of 80 cases of oral submucous fibrosis (40 test subjects and 40 controls) were included in this study and 100% acquiescence was reported at the end of the test period. Results: Mild dizziness and gastric irritation were the only untoward symptoms reported in 2 of the volunteers in the study group during this trial. These were managed by diet protocols. A review of the patients and controls was done at an interval of every 4 weeks for 3 months. The subjective and objective measurements were recorded. The follow-up data at each visit concerning each other and to base-line values were calibrated using nonparametric tests of the Chi-Square test and Mann-Whitney. Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (u value =1.137, p = 0.260), tongue protrusion (u value = 0.262, p = 0.794 and cheek flexibility (u value =0.990, p = 0.326). Subjective symptoms of burning sensation of mouth (U value = 2.673, p = 0.008), pain on opening the mouth (U value = 4.320, p < 0.0001), difficulty in swallowing and difficulty in the speech were also recorded. Conclusion: This study showed the effectiveness of pentoxifylline as an additional therapy in the routine management of oral submucous fibrosis.

In-silico analysis of heat shock protein 47 for identifying the novel therapeutic agents in the management of oral submucous fibrosis.

Background: Heat shock proteins-47 (HSP47) is a collagen specific molecular chaperone, involved in the processing and/or secretion of procollagen. It seems to be regularly upregulated in various fibrotic or collagen disorders. Hence, this protein can be a potential target for the treatment of various fibrotic diseases including oral submucous fibrosis (OSF), which is a collagen metabolic disorder of oral cavity and whose etiopathogeneic mechanism and therapeutic protocols are still not well documented. Aim: The aim of this study is to identify the novel therapeutic agents using in-silico methods for the management of OSF. Objectives: The objectives of this study are to identify the binding sites of HSP47 on the collagen molecule and to identify the lead compound with anti-HSP47 activity from the library of natural compounds, using in-silico methodology. Materials and Methods: The web-based and tool based in-silico analysis of the HSP47 and collagen molecules are used in this study. The crystal structure of collagen and HSP47 were retrieved from Protein Data Bank website. The binding site identification and the docking studies are done using Molegro Virtual Docker offline tool. Results: Out of the 104 Natural compounds, six ligands are found to possess best binding affinity to the binding amino acid residues. Silymarin binds with the 4AU2A receptor and the energy value are found to be −178.193 with four Hbonds. The other best five natural compounds are hesperidin, ginkgolides, withanolides, resveratrol, and gingerol. Our findings provide the basis for the in-vitro validation of the above specified compounds, which can possibly act as "lead" molecules in designing the drugs for OSF. Conclusion: HSP47 can be a potential candidate to target, in order to control the production of abundance collagen in OSF. Hence, the binding sites of HSP47 with collagen are identified and some natural compounds with a potential to bind with these binding receptors are also recognized. These natural compounds might act as anti-HSP47 lead molecules in designing novel therapeutic agents for OSF, which are so far unavailable.

Oral submucous fibrosis in India: Are we progressing.

Oral submucous fibrosis (OSMF) a condition first described in the 1950s in the modern literature still remains elusive of a cure. For many years this condition had been confined to countries like India, Pakistan, Bangladesh, etc., but now this condition is being reported from Western countries as well. Inspite of intensive research over the years into the etiologic factors of OSMF, a single etiologic factor cannot be pointed out with certainty rather several causative factors have been proposed. Patients suffering with OSMF initially present with a blanched or marble-like pale mucosa, vesiculations, and also intolerance to hot and spicy food. Gradually, the patient may develop fibrous bands in the buccal and labial mucosa which causes a restriction in opening the mouth. The evidence for the various treatment modalities for OSMF is weak hence better documentation of the studies performed with standardized criteria is required. The current review aims to refresh our knowledge regarding OSMF from an Indian perspective and make a few suggestions to fill the lacunae in this field.

Evaluation of the effect of newer antioxidant lycopene in the treatment of oral submucous fibrosis.

Background and Objective: Oral submucous fibrosis (OSMF) is a well-known premalignant condition encountered in Indian population. Although the disease is advancing rapidly, its reliable treatment modality for its various stages has not yet evolved. The aim of the present study is to compare the effect of newer antioxidant lycopene with a placebo in conjunction with the cessation of causative habit in the treatment of OSMF. Materials and Methods: The study group included 92 patients with OSMF. The OSMF diagnosis was established through a composite of accepted clinical and histopathological characteristics. Out of 92, 46 patients were given lycopene and remaining 46 were on placebo drug. Lycopene group patients received 8 mg Lycored TM per day in two divided doses of 4 mg each, while placebo group patients received placebo tablet twice a day. Patients were examined for changes in mouth opening and other clinical symptoms of OSMF during three months and were followed up for next two months. Results: Lycopene was found to be significantly efficacious in the amelioration of signs and symptoms of OSMF. It was effective in reducing the objective signs of OSMF as demonstrated by the improved maximal mouth opening, percentage of which was 69.56%(P<0.05). Interpretation and Conclusion: Reactive oxygen compounds or free radicals have been implicated as one of the major harmful factors for premalignant and malignant conditions. Present study concludes that lycopene, a newer antioxidant, appears to be a very promising drug in the management of OSMF.

Evaluation of oral submucous fibrosis using ultrasonographic technique: A new diagnostic tool.

Aim: The aim of this study is to evaluate oral submucous fibrosis (OSMF) by clinical and histopathological examination, and compare the results with those from ultrasonographic technique. Materials and Methods: 30 clinically diagnosed OSMF patients were subjected to both ultrasonographic and histopathological evaluation before treatment. Later, only ultrasonographical examination was done during 4 th and 8 th week of treatment. Prognosis of the lesion for the treatment was evaluated. Peak systolic velocity (PSV) of blood in the lesional area was statistically analyzed. 10 normal individuals without any mucosal lesions were considered as the control group. Results: In normal individuals, ultrasonography delineates normal mucosa with uniform fine mottled appearance with interspersed hypoechoic areas. Color Doppler and spectral Doppler depicts uniform distribution of blood vessels and normal peak systolic velocity of blood respectively. All OSMF patients were diagnosed upon clinical and histopathological examination. Clinical examination revealed 14 individuals with unilateral palpable fibrotic bands and 16 individuals with bilateral fibrotic bands whereas, ultrasonographic evaluation revealed 6 individuals with unilateral fibrotic bands and 24 individuals were with bilateral fibrotic bands, which was statistically significant. Ultrasonography demonstrated number, length and thickness of the fibrotic bands. Color Doppler and spectral Doppler showed decreased vascularity and PSV in lesional area. Prognosis evaluation revealed 25 cases of good prognosis and 5 cases were showed poor prognosis. Wilcoxon Signed Ranks Test revealed no significant difference of PSV was seen in poor prognosis patients. Conclusion: Ultrasonography is a non-invasive diagnostic tool for OSMF. It could be a better diagnostic tool compared to clinical and histopathological examination.

In vivo autofluorescence characteristics of pre- and post-treated oral submucous fibrosis: A pilot study.

Aims and Objectives: To compare the autofluorescence spectra of oral submucous fibrosis (OSF) with normal mucosa, the autofluorescence spectra of OSF before and after treatment with intralesional dexamethasone and hyaluronidase, the clinical improvement following treatment with the changes in autofluorescence spectra and to prove that autofluorescence spectroscopy is a good method for diagnosis and assessment of treatment effectiveness in OSF. Materials and Methods: The study was conducted at the Department of Oral Medicine and Radiology, Tamilnadu Government Dental College and Hospital, Chennai and Division of Medical Physics and Lasers, Department of Physics, Anna University, Chennai in 20 patients seeking medical management for symptomatic OSF and 20 patients who had dental caries only without any oral mucosal diseases and oral habits were used as normal controls. Their ages ranged from 20 to 40 years, including both male and female. In vivo fluorescence emission spectra were obtained using a handheld optical fiber probe attached to a Fluoromax-2 spectrofluorometer. Results: The fluorescence spectrum of OSF had an intense fluorescence emission at 385 nm with a secondary emission peak at 440 nm compared with that of the normal oral mucosa. The average fluorescence spectrum of the post treated OSF mucosa had a lesser intensity around 385 nm and a higher intensity around 440 nm than that of the pre treated OSF mucosa, thereby mimicking the normal oral mucosa. All the three clinical parameters (maximal mouth opening, tongue protrusion and the severity of burning sensation) showed a high statistical significance, with P < 0.001, as in the case of classification of pre treated OSF mucosa from the post treated OSF mucosa using the autofluorescence technique. Conclusion: The change in the fluorescence emission spectrum for both normal and OSF mucosa before and after treatment can be explained by analyzing the changes in the fluorescence intensity of the endogenous fluorophores.

Pentoxifylline therapy: a new adjunct in the treatment of oral submucous fibrosis.

OBJECTIVE: This study was designed to determine the effect of pentoxifylline (Trental) on the clinical and pathologic course of oral submucous fibrosis. This drug is a methylxanthine derivative that has vasodilating properties and was envisaged to increase mucosal vascularity. STUDY DESIGN: This investigation was conducted as a randomized clinical trial incorporating a control group (Standard drug group SDG, multivitamin, and local heat therapy) in comparison to pentoxifylline test cases (Experimental drug group EDG, 400mg 3 times daily, as coated, sustained release tablets). The stipulated treatment period was 7 months and a total of 29 cases of advanced fibrosis (14 test subjects and 15 age and sex matched diseased controls) were included in this study and 100% compliance was reported at the end ofthe test period. RESULTS: Mild gastric irritation that could be managed by diet protocols was the only untoward symptom reported during this trial. Review of the patients and controls was done at an interval of 30 days and subjective and objective measurements were recorded. The follow up data at each visit with respect to each other and to base-line values was calibrated using a nonparametric test of Mann-Whitney (Kruskal-Wallis test). Significant comparisons with regard to improvement were recorded as objective criteria of mouth opening (t=11.285, p= 0.000), tongue protrusion (t= 3.898, p = 0.002), and relief from perioral fibrotic bands (p = 0.0001554). Subjective symptoms of intolerance to spices (p = 0.0063218), burning sensation of mouth (p = 0.0005797), tinnitus (p=0.000042), difficulty in swallowing (p=0.0000714). and difficulty in speech (p=0.0000020) were also recorded significant improvement at the end of the trial period. CONCLUSION: This pilot investigation points to the effectiveness of pentoxifylline as an adjunct therapy in the routine management of oral submucous fibrosis.