Mangostanin hyaluronic acid hydrogel as an effective biocompatible alternative to chlorhexidine.

Periodontal disease (PD) prevention and treatment products typically demonstrate excellent antibacterial activity, but recent studies have raised concerns about their toxicity on oral tissues. Therefore, finding a biocompatible alternative that retains antimicrobial properties is imperative. In this study, a chemically modified hyaluronic acid (HA) hydrogel containing mangostanin (MGTN) was developed. Native HA was chemically modified, incorporating amino and aldehyde groups in different batches of HA, allowing spontaneous crosslinking and gelation when combined at room temperature. MGTN at different concentrations was incorporated before gelation. The structure, swelling characteristics MGTN release, rheological parameters, and in vitro degradation performance of the loaded hydrogel were first evaluated in the study. Then, antimicrobial properties were tested on Porphyromonas gingivalis and its biocompatibility in 3D-engineered human gingiva. HA hydrogel was very stable and showed a sustained release for MGTN for at least 7 days. MGTN-loaded HA hydrogel showed equivalent antimicrobial activity compared to a commercial gel of HA containing 0.2 % chlorhexidine (CHX). In contrast, while MGTN HA hydrogel was biocompatible, CHX gel showed high cytotoxicity, causing cell death and tissue damage. Modified HA hydrogel allows controlled release of MGTN, resulting in a highly biocompatible hydrogel with antibacterial properties. This hydrogel is a suitable alternative therapy to prevent and treat PD.

Microfluidic Rheology: An Innovative Method for Viscosity Measurement of Gels and Various Pharmaceuticals.

Measuring the viscosity of pharmaceutical dosage forms is a crucial process. Viscosity provides information about the stability of the composition, the release rate of the drug, bioavailability, and, in the case of injectable drug formulations, even the force required for injection. However, measuring viscosity is a complex task with numerous challenges, especially for non-Newtonian materials, which include most pharmaceutical formulations, such as gels. Selecting the appropriate shear rate is critical. Since viscosity in many systems is highly temperature-dependent, stable temperature control is necessary during the measurement. Using microfluidics technology, it is now possible to perform rheological characterization and conduct fast and accurate measurements. Small sample volumes (even below 500 µL) are required, and viscosity determination can be carried out over a wide range of shear rates. Nevertheless, the pharmaceutical application of viscometers operating on the principle of microfluidics is not yet widespread. In our work, we compare the results of measurements taken with a microfluidic chip-based viscometer on different pharmaceutical forms (gels, solution) with those obtained using a traditional rotational viscometer, evaluating the relative advantages and disadvantages of the different methods. The microfluidics-based method enables time- and sample-efficient viscosity analysis of the examined pharmaceutical forms.

Formulation of 1% α-mangostin in orabase gel induces apoptosis in oral squamous cell carcinoma.

BACKGROUND: Plant-derived compounds have chemopreventive properties to be used as alternative medicine. Pericarp of Mangosteen (Garcinia mangostana Linn.), a tropical fruit in Southeast Asia contains a phytochemical α-mangostin (α-MG) that demonstrates potent anticancer effects against various types of cancer. α-MG has been reported to be the most effective agent in human cancer cell lines. The objectives of this study were to develop oral gel formulations containing α-MG and determine their (1) anticancer activity, (2) anti-HPV-16 and antimicrobial activities, (3) nitric oxide (NO) inhibitory activity, and (4) wound healing effect. METHODS: Formulations of oral gel containing α-MG were developed. Anticancer activity on SCC-25 was assessed. Apoptotic induction was determined using flow cytometry technique. Antiviral activity against HPV-16 pseudovirus and antimicrobial activity against S. mutans, P. gingivalis and C. albicans were investigated. NO inhibition was carried out. Fibroblast cell migration was determined by in vitro scratch assay. RESULTS: The formulation of 1% α-MG in orabase gel demonstrated anticancer activity by promoting apoptosis in SCC-25. The induction of apoptotic activity was dose dependent with pronounced effect in late apoptosis. The formulation appeared to reduce cell viability of oral keratinocytes (OKC). At CC50 it showed an inhibition against HPV-16 pseudovirus infection. The formulation had no antimicrobial activity against S. mutans, P. gingivalis and C. albicans. No significant NO inhibitory activity and wound healing effects were found. CONCLUSIONS: 1% α-MG in orabase gel exhibited anticancer activity by inducing apoptosis although low level of cytotoxicity observed in OKC was present. The appropriate carrier for novel nano-particles targeting cancer cells should be further investigated.

Jasminum grandiflorum oral gel as an add-on to standard of care in radiation induced grade 2 oral mucositis - an open label pilot clinical trial.

BACKGROUND: Radiation-induced oral mucositis is one of the most critical dose-limiting toxicities associated with radiation therapy for oral cancer which can result in treatment interruption and compromise the quality of the life of cancer patients. Jati (Jasminum grandiflorum) is used in Ayurveda to treat oral conditions like stomatitis and mouth ulcers. OBJECTIVE: To test the feasibility of Jati oral gel as an add on therapy in grade 2 radiation-induced oral mucositis. MATERIALS AND METHODS: A prospective, open-label, non-randomised pilot trial was conducted on 20 patients with grade 2 radiation-induced oral mucositis at a tertiary cancer hospital. The control group received sodium bicarbonate mouthwash 4-5 times daily as the standard of care, while the intervention arm also received Jati oral gel twice daily. We used the ImageJ software for objective assessment and the Visual Analogue Scale for subjective pain assessment. The study was continued for 15 days or until the mucositis progressed to grade 3 or resolved to grade 1. RESULT: There was a significant reduction in the mean pain score and mean area of mucositis in the intervention group compared to the control group. CONCLUSION: Jati oral gel is a suitable medicament as an add-on therapy in managing grade 2 radiation-induced oral mucositis.

An oral gel suitable for swallowing: The effect of micronization on the gel properties and microstructure of κ-carrageenan.

κ-Carrageenan (κ-Car) is an important material for preparing food gels and hydrogels. However, κ-Car gel has issues with high hardness and low water-holding capacity. Modification strategy of micronization is proposed for the first time to explore its influence on texture properties and gelling process of κ-Car gel, and to investigate the feasibility of κ-Car as a food matrix with low strength. κ-Car undergoing 60 min of micronization, the d(0.9) decreased by 79.33 %, SBET and Vtotal increased by 89.23 % and 95.27 %. The swelling rate and degree of gelling process increased significantly, and the microstructure changed from loose large pores to dense small pores resembling a "honeycomb". Importantly, the hardness of gel-60, Milk-60 and PNS-60 decreased by 72.52 %, 49.25 % and 81.37 %. In addition, WHC of gel-60, Milk-60 and PNS-60 was improved. IDDSI tests showed that κ-Car gels, milk gels and PNS gels can be categorized as level 6 (soft and bite-sized), except for PNS-60, which belongs to level 5 (crumbly and moist). Furthermore, the texture and bitter masking effect of milk gels and PNS gels were improved. In conclusion, this study demonstrated that micronization can be a novel approach to improve the gel properties of κ-Car, laying the groundwork for developing dysphagia foods.

An In Vitro Evaluation of Anti-inflammatory and Antioxidant Activities of Cocos nucifera and Triticum aestivum Formulation.

Background Medicinal plants are traditionally used in Ayurveda, Unani medicine, and Siddha as primary sources of drugs, and mankind has exploited the therapeutic properties of these herbs throughout history. Coconut (Cocos nucifera), a common ingredient of Indian sub-continental cuisine, has been proven to possess various medicinal properties; similarly, wheatgrass (Triticum aestivum) is of greater medicinal value and is known as the powerhouse of nutrients and vitamins. These have been used individually, but there is limited data on the synergistic use of these products. Thus, the present in vitro study was designed to prepare an oral gel from the extract of C. nucifera and T. aestivum and to assess its cumulative anti-inflammatory and antioxidant activity. Materials and methods C. nucifera extract and T. aestivum extract were prepared separately, and gel formulation was done. The formulated gel was tested for its anti-inflammatory and antioxidant activity. Results The results of the present study demonstrated that the anti-inflammatory property of the gel formulation was greater as compared to the standard (diclofenac), with the highest percentage of inhibition of 90.1% at 50 µl. With regard to the antioxidant property, we found that it was comparable to the standard (ascorbic acid) at various concentrations, with greater activity at 50 µl. Conclusion The oral gel formulation of coconut (C. nucifera) and wheatgrass (T. aestivum) showed better anti-inflammatory and a comparable antioxidant activity. Thus, this formulation may be employed as an adjunct to the commercially available oral gel preparations.

Assessment of thyme honey oral gel for the prevention of adriamycin and cyclophosphamide chemotherapy-induced oral mucositis in patients with breast cancer.

PURPOSE: Oral mucositis (OM) is a common complication of cancer treatment that has an impact on a patient's quality of life and the outcome of cancer therapy. This trial evaluated the effect of thyme honey oral gel for the prevention of chemotherapy-induced OM. METHODS: One hundred ten breast cancer patients who received their first cycle of chemotherapy with adriamycin (60 mg/m2) and cyclophosphamide (600 mg/m2) were randomly recruited into two groups: group A were patients who followed general oral hygiene recommendations and rinsing saline 3 times a day, and group B were patients with similar protocol but supplied with our formulated oral gel to be applied 2 to 4 times a day. Patients were assessed by the World Health Organization (WHO) oral mucositis grading scales and self-assessment daily questionnaire. RESULTS: The use of thyme honey was associated with diminishing incidence of OM grade ≥ 2 (95% CI, 0.12 to 0.90; P = 0.030), duration of OM (- 3.36 days; 95% CI, - 5.50 to - 1.22; P = 0.037) and delayed occurrence of OM grade ≥ 2 (95% CI, 0.10 to 0.80; P = 0.017). CONCLUSION: Thyme honey can be considered as a prophylactic agent for OM and decrease the severity of its symptoms. TRIAL REGISTRATIONS: This protocol was registered at the Iranian Registry of Clinical Trials: registration number IRCT201506063106N25, on June 12, 2015; approved by the institutional review board at the Deputy of Research, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; and approved by the Ethics Committee of Medical Researches of Pharmaceutical Sciences Branch of Islamic Azad University, Tehran, Iran-reference number 5936, on August 17, 2014.

Efficacy of polyacrylate silver salt/polyvinylpyrrolidone-based liquid oral gel in management of concurrence chemoradiotherapy-induced oral mucositis.

BACKGROUND/PURPOSE: Acute oral mucositis (OM) is a painful complication of concurrent chemoradiotherapy (CCRT). This severe adverse symptom may impact on patient's quality of life, lead to malnutrition. Thus, finding more effective methods in OM management is very important. The purpose of this study is to evaluate the efficacy of polyacrylate silver salt/Polyvinylpyrrolidone-based liquid oral gel (named as polyacrylate silver salt oral gel) in improving the symptomatic relief of CCRT-induced oral mucositis and oral dysfunction in neck and head cancer patients. METHODS: In this study, 24 oral cancer patients underwent CCRT and having OM grade 2 or higher were randomly assigned into the test group and the control group. Both groups followed Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines for the management of mucositis, but adding rinsing with 15 g oral gel right after oral hygiene treaded the test group. Clinical OM and oral function were assessed weekly for 4 consecutive weeks till 5-10 days after the completion of radiotherapy. For evaluation, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 was used for collecting the data of OM grade. RESULTS: The results showed that polyacrylate silver salt oral gel had better effect for relieving the oral mucositis. There were statistically significant differences in OM grades (1.59 vs. 2.8, p < 0.0001) between the test group and the control group. CONCLUSION: Our clinical studies demonstrated that polyacrylate silver salt oral gel is an effective interventional option in terms of rapid mucositis healing.

A Curcumin-Based Oral Gel Has Potential Protective Efficacy against Oral Mucositis: In Vitro Study.

Oral mucositis is a common distressing complication of cancer therapy, characterised by painful sores within the oral cavity. Current management options offer limited symptomatic relief. Curcumin, a natural polyphenolic compound with recognised anti-inflammatory and antioxidant properties, has emerged as a potential protective agent against oral mucositis. This study explores the therapeutic potential of curcumin in mitigating the impact of oral mucositis by investigating a commercially available curcumin-based oral gel, PerioGold®. Liquid chromatography-tandem mass spectrometry was used to characterise the main constituents of PerioGold®. The cytotoxicity of curcumin constituent was investigated in four cell lines: primary oral keratinocytes (HOKs), immortalised oral keratinocytes (OKF6), dysplastic oral keratinocytes (DOKs), and oral squamous cell carcinoma cells (PE/CA-PJ15). Concentrations of hydrogen peroxide were optimised to develop in vitro models that mimic oral mucositis. The inhibitory effects of PerioGold® against the production of reactive oxygen species were assessed using a designated kit. OKF6 cells were the most sensitive to oxidative stress, while PE/CA-PJ15 cells showed the highest resistance. Pretreatment of the investigated cells for 24 h with PerioGold® demonstrated a significant antioxidative effect in all cells based on a dose-response pattern. PerioGold® exhibits clinical potential for protecting against oxidative stress, warranting further individualised clinical investigations.

Formulation of a Gastroretentive In Situ Oral Gel Containing Metformin HCl Based on DoE.

A gastroretentive in situ oral gel containing metformin hydrochloride (Met HCl) was prepared based on sodium alginate (Sod ALG), calcium carbonate, and hydroxyethylcellulose (HEC). The optimal composition of the formulation was explored based on the design of experiments (DoE). First, a 32 full factorial design was used for formulation E1 to determine proper composition of Sod ALG and calcium carbonate. Second, a circumscribed central composite design was employed to add HEC as a thickening agent (formulation E2). The dissolution rates at 15, 30, 60, 120, and 240 min were used as responses. Partial least squares regression analysis indicated the effect of each component in delaying the release of Met HCl in the oral gel formulation. The optimized formulation E2-08 consisting of 1.88% Sod ALG, 0.63% HEC, and 1.00% calcium carbonate and two more formulations, E2-10 and E2-12 conformed to USP monograph for extended release. Other physicochemical properties, including floating lag time and duration, viscosity, and pH, measured for each batch and FT-IR spectrometry analysis showed no unexpected interaction between Met HCl and excipients. The current study suggests the potential use of a gastroretentive in situ oral gel for Met HCl helping patient compliance. This study highlights that a systematic approach based on DoE allows the formulation optimization.

Oral gel loaded with penciclovir-lavender oil nanoemulsion to enhance bioavailability and alleviate pain associated with herpes labialis.

Herpes labialis, caused by herpes simplex virus type 1, is usually characterized by painful skin or mucosal lesions. Penciclovir (PV) tablets are found to be effective against herpes labialis but suffer from poor oral bioavailability. This study aimed to combine the benefits of PV and lavender oil (LO), which exhibits anesthetic activity, in the form of a self-nanoemulsifying drug delivery system (SNEDDS) for the treatment of herpes labialis. Toward this purpose, LO (oil), Labrasol:Labrafil M1944 CS in the ratio of 6:4 (surfactant mixture), and Lauroglycol-FCC (co-surfactant, selected based on the solubility of PV) were evaluated as the independent factors using a distance quadratic mixture design. The formulation was optimized for the minimum globule size and maximum stability index and was determined to contain 14% LO, 40.5% Labrasol:Labrafil 1944 (6:4), and 45.5% Lauroglycol-FCC. The optimized PV-LO-SNEDDS was embedded in chitosan hydrogel and the resulting formulations coded by (O3) were prepared and evaluated. The rheological studies demonstrated a combined pseudoplastic and thixotropic behavior with the highest flux of PV permeation across sheep buccal mucosa. Compared to a marketed 1% PV cream, the O3 formulation exhibited a significantly higher and sustained PV release, nearly twice the PV permeability, and a relative bioavailability of 180%. Overall, results confirm that the O3 formulation can provide an efficient delivery system for PV to reach oral mucosa and subsequent prolonged PV release. Thus, the PV-LO-SNEDDS embedded oral gel is promising and can be further evaluated in clinical settings to establish its therapeutic use in herpes labialis.

Translation into Practice: Dextrose Gel Treatment for Neonatal Hypoglycemia to Reduce NICU Admissions and Increase Breastfeeding Exclusivity.

BACKGROUND: Oral dextrose gel is an evidence-based treatment that has been shown to reduce NICU admissions and support exclusive breastfeeding. PURPOSE: We summarize a knowledge translation project to introduce dextrose 40 percent oral gel to treat hypoglycemia or hyperglycemia. Implementation took place during the months of May, June, and July 2017. RESULTS: Through chart audit, rates for NICU admissions and exclusive breastfeeding were measured for a three-month period before implementation and the three-month period after implementation.There were 234 doses indicated, 128 doses given, 93 doses missed, and 13 doses declined by parents in the first three months of implementation. Admission rates to the NICU for the groups audited were 13 percent in 2016 and 6 percent in 2017.Principles of knowledge translation were used to successfully introduce this change. Centers providing maternal newborn care should consider similar projects to enable introduction.

Central serous retinopathy associated with topical oral corticosteroid use: a case report.

BACKGROUND: Oral topical corticosteroid gels are widely used in dental medicine. Case studies of central serous retinopathy have been reported following administration of corticosteroids, but none so far coinciding with the use of topical fluocinonide gel. This case report further contributes to the database of potential risks of corticosteroid use. CASE PRESENTATION: A 40-year-old South Asian woman presented with decreased vision, pigment epithelial detachments, and serous retinal detachments in both eyes 1 month after starting treatment with topical fluocinonide 0.05%, a topical oral corticosteroid gel. Her condition resolved 6 months after discontinuing the use of the steroid. CONCLUSIONS: To the best of our knowledge, this is the first case of idiopathic central serous retinopathy associated with the use of oral fluocinonide gel. Discontinuing the use of the steroid may result in resolution of the serous retinal detachment and improvement of visual symptoms. Patients and their doctors who prescribe this medication should be aware of this association.

A Randomized Clinical Trial to Measure Mouth Moisturization and Dry Mouth Relief in Dry Mouth Subjects Using Dry Mouth Products.

OBJECTIVES: This study examined ratings of two subjective aspects (moisturization and dry mouth relief) that may be changed following the use of dry mouth relief products (an oral gel, an oral rinse, or a mouth spray), in comparison to water over a period of four hours following a single supervised use on two separate occasions. METHODS: This was a single-center, two site, randomized, examiner blind, four treatment arm, stratified (by dry mouth screening score at baseline), parallel group study in healthy subjects with a self-reported feeling of dry mouth. Prior to product use, subjects rated their current subjective perception of moisturization and dry mouth on an 11-point scale. Subjects then rated the two questions immediately after product use and 30, 60, 90, 120, and 240 minutes later. At the 240-minute time point, subjects also rated global efficacy questions regarding "overall" and "long-lasting" moisturization and dry mouth relief, and overall product opinion. Subjects then used their assigned products at home for three days and the procedures were repeated on Day 4. RESULTS: In total, 300 subjects were randomized to treatment. Compared with water, all test products showed statistically significantly greater improvements over baseline on both Day 1 and Day 4 at most time points, on the area under the curve from baseline for the moisturization and dryness questions, and after 240 minutes for the global efficacy and overall opinion assessments (all p < 0.05). There was a statistically significant difference between the pre-dosing assessments on Day 1 versus Day 4 (p < 0.001) for both efficacy questions. Products were generally well-tolerated. CONCLUSIONS: Three different types of dry mouth relief products were shown to provide significant relief of dry mouth and increased feelings of moisturization compared to water using subjective questionnaires.

Anti-inflammatory and healing action of oral gel containing borneol monoterpene in chemotherapy-induced mucositis in rats ( Rattus norvegicus )

ABSTRACT The aim of this study was to investigate the effect of gels containing the monoterpene borneol in induced oral mucositis using an animal model. Gels were prepared with borneol at 1.2% and 2.4% (w/w). Oral mucositis was induced by administration of three doses of 5-fluorouracil (30 mg/kg, i.p.) and injury with acetic acid (50%, v/v) soaked in filter paper applied to right cheek mucosa for 60s. Four subgroups comprising 12 animals each were formed. Six animals from each group were sacrificed at days seven and fourteen after oral mucositis induction. Mucous samples were processed and stained with hematoxylin-eosin and Masson's Trichrome. The semiquantitative evaluation involved observation of inflammatory parameters. ImageJ® software was used in the quantitative evaluation. For statistical analyses, Two-way ANOVA, followed by Tukey's post-test (p <0.05), were employed. Borneol 2.4% gel proved effective in the treatment of oral mucositis with statistically significant differences between groups for angiogenesis control, inflammatory cell count reduction and percentage neoformed collagen increase. The confirmation of anti-inflammatory and healing action of borneol in oral mucositis in rats renders it a good marker for predicting this activity for plant extracts rich in this substance

Innovation of natural essential oil-loaded Orabase for local treatment of oral candidiasis.

PURPOSE: Oral candidiasis may be manifested in the oral cavity as either mild or severe oral fungal infection. This infection results from the overgrowth of Candida species normally existing in the oral cavity in minute amounts based on many predisposing factors. Several aspects have spurred the search for new strategies in the treatment of oral candidiasis, among which are the limited numbers of new antifungal drugs developed in recent years. Previous studies have shown that thyme and clove oils have antimycotic activities and have suggested their incorporation into pharmaceutical preparations. This study aimed to investigate the possibility of the incorporation and characterization of essential oils or their extracted active ingredients in Orabase formulations. METHODS: Orabase loaded with clove oil, thyme oil, eugenol, and thymol were prepared and evaluated for their antifungal activities, pH, viscosity, erosion and water uptake characteristics, mechanical properties, in vitro release behavior, and ex vivo mucoadhesion properties. RESULTS: All prepared bases showed considerable antifungal activity and acceptable physical characteristics. The release pattern from loaded bases was considerably slow for all oils and active ingredients. All bases showed appreciable adhesion in the in vitro and ex vivo studies. CONCLUSION: The incorporation of essential oils in Orabase could help in future drug delivery design, with promising outcomes on patients' well-being.