Tau-Marin Mucoadhesive Gel for Prevention and Treatment of Gum Diseases.

An innovative and stable probiotic-containing mucoadhesive gel (AL0020), integrated with botanical extracts, has been developed to rebalance the dysbiosis associated with periodontal diseases. Tau-Marin gel, prepared with anhydrous ingredients to prevent the replication of bacteria and ensure good stability over time, was tested against some pathogenic bacteria, belonging to the so-called "red complex", recognized as the most important pathogens in plaque specimens, adherent to the epithelial lining of periodontal pockets. This lipogel was tested in vitro, in a physiological solution (PS) and in a simulated saliva (SS), for up to 8 h, to monitor its ability to release probiotics over time. Probiotics were enumerated through two different techniques, Lacto-Counter Assay (LCA) and Colony Forming Unit (CFU). A detailed physico-chemical profile of AL0020 and its in vitro efficacy in protecting activity against pathogenic bacteria as well as soothing or irritative effect on gingival epithelium were reported. Moreover, a clinical-dermatological trial on 20 volunteers using the product once a day for 30 days was also performed, where the efficacy of the gel in the control of gum disorders was observed.

Comparative clinical evaluation of a local drug delivery of cranberry and garcinia fruit gel with tetracycline fibers for amelioration of periodontitis: A split mouth study.

Background: The present study formulates and evaluates a polyberry gel comprising extracts of cranberry (Vaccinium macrocarpon) and brindle berry (Garcinia cambogia) in patients suffering from chronic periodontitis. Materials and Methods: The polyberry gel was evaluated for various physicochemical parameters, in vitro permeability and stability, and the active phytoconstituents were quantified by High-performance thin layer chromatography (HPTLC). Total phenolic content, total antioxidants, and ascorbic acid were estimated in the two extracts by in vitro assays. Patients suffering from chronic periodontitis with probing pocket depth (PPD) up to 5 mm were divided into 3 groups of 21 patients each and treated with scaling and root planing (SRP) or SRP followed by subgingival placement of polyberry gel or tetracycline fibers (standard). Plaque Index (PI), Gingival Index (GI), PPD, Clinical Attachment Level (CAL), and the salivary aspartate aminotransferase (AST) and C-reactive protein (CRP) levels were recorded at baseline and after 1 month. Results: A significant (P < 0.01) reduction in the periodontic disease parameters was observed in the standard and gel-treated groups between their baseline and 1-month time-interval readings. The polyberry gel treatment significantly (P < 0.05 for AST and P < 0.01 for the rest) attenuated the periodontitis-elevated PI, GI PPD, CAL, AST and CRP levels when compared with SRP at the end of the study and was comparable with tetracycline. Conclusion: The amelioration of periodontitis and gingival inflammation may be attributed to the potent antioxidant activity of the polyphenolic phytoconstituents of the gel. The polyberry gel may thus be used as a safe adjunct to SRP/tetracycline in chronic periodontitis.

Development of a Novel Histatin-5 Mucoadhesive Gel for the Treatment of Oral Mucositis: In Vitro Characterization and In Vivo Evaluation.

Antimicrobial peptides have appeared to be promising candidates for therapeutic purposes due to their broad antimicrobial activity and non-toxicity. Histatin-5 (Hst-5) is a notable salivary antimicrobial peptide that exhibited therapeutic properties in the oral cavity. Oral mucositis is an acute inflammation of the oral cavity, following cancer therapy. The current treatment methods of oral mucositis have low effectiveness. The aim of this study was to design, formulate and characterize a mucoadhesive gel delivery system for Hst-5 usage in the treatment of oral mucositis. Carbopol 934 and hydroxypropyl methylcellulose (HPMC) have been used in the development of a Hst-5 mucoadhesive gel that was optimized by using Box-Behnken design. The optimized formulation was evaluated in-vitro, based on mucoadhesive strength, viscoelasticity, spreadability, release rate, peptide secondary structure analysis, antimicrobial activity, and storage stability. The efficacy of Hst-5 gel was assessed in vivo in a chemotherapy-induced mucositis model. The results showed a sustained release of Hst-5 from the new formulation. Hst-5 gel exerted antimicrobial activity against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. The histopathological, immunohistochemical and statistical analysis showed that the Hst-5 gel had wound healing activity in vivo. The findings of this study indicate that the mentioned compound possesses promising potential as a novel and efficient therapeutic agent in managing oral mucositis. Moreover, the results suggest that the compound is commercially feasible for further development and utilization.

Formulation and Evaluation of Prednisolone Sodium Metazoate-Loaded Mucoadhesive Quatsomal Gel for Local Treatment of Recurrent Aphthous Ulcers: Optimization, In Vitro, Ex Vivo, and In Vivo Studies.

This study aims to formulate a buccal mucoadhesive gel containing prednisolone sodium metazoate-loaded quatsomes for efficient localized therapy of recurrent aphthous ulcers. Quatsomes were prepared using a varied concentration of quaternary ammonium surfactants (QAS) and cholesterol (CHO). A 23 factorial design was conducted to address the impact of independent variables QAS type (X1), QAS to CHO molar ratio (X2), and sonication time (X3). The dependent variables were particle size (PS; Y1), polydispersity index (PDI; Y2), zeta potential (ZP; Y3), entrapment efficiency percent (EE%; Y4) and percent of drug released after 6 h (Q6%: Y5). Then, the selected quatsomes formula was incorporated into different gel bases to prepare an optimized mucoadhesive gel to be evaluated via in vivo study. The PS of the developed quatsomes ranged from 69.47 ± 0.41 to 113.28 ± 0.79 nm, the PDI from 0.207 ± 0.004 to 0.328 ± 0.004, ZP from 45.15 ± 0.19 to 68.1 ± 0.54 mV, EE% from 79.62 ± 1.44 to 98.60% ± 1.22 and Q6% from 58.39 ± 1.75 to 94.42% ± 2.15. The quatsomal mucoadhesive gel showed rapid recovery of ulcers, which was confirmed by the histological study and the evaluation of inflammatory biomarkers. These results assured the capability of the developed quatsomal mucoadhesive gel to be a promising formulation for treating buccal diseases.

Development and in vitro characterization of a mucoadhesive gel with Moringa oleifera extract for periodontal drug delivery.

Background: Extensive in vitro and in vivo research has been conducted in the previous decades to analyze the effectiveness of medicinal plants in the treatment of periodontal diseases. Moringa oleifera is a highly potent medicinal plant that has anti-inflammatory and immuno-modulatory properties. In our study, we aim to design, formulate, and evaluate the antibacterial efficacy of M. oleifera extract for local drug delivery (LDD) as periodontal treatment. Materials and Methods: This study was an in vitro experimental model. M. oleifera extract was prepared using a maceration process with powdered dried leaves of M. oleifera and 70% ethanol. The minimum inhibitory concentration (MIC) of Moringa extract against Porphyromonas gingivalis was assessed using the broth dilution method. The gel was prepared with the obtained MIC of Moringa extract and a combination of polymers- Polyethylene glycol 6000, Carbopol 940, and Chitosan. Further, the formulated gel was subjected to in vitro characterization by thermodynamic stability tests, pH determination, and syringeability test. Viscosity was determined using Brookfield DV-II + Viscometer. Mucoadhesive strength was determined using a fabricated mucoadhesive strength test apparatus. Results: M. oleifera leaves extract possesses a bactericidal effect against P. gingivalis even at a low amounts of 25 µg/ml and so is a potent botanical extract for the formulation of LDD agents for periodontal diseases. The formulation shows adequate stability, good mucoadhesiveness, and controlled drug release, on incorporating the herbal extract into the blank gel. Conclusion: The M. oleifera leaves extract possesses a bactericidal effect against P. gingivalis which has been suggested to be the keystone pathogen in the etiopathogenesis of periodontitis. Hence, M. oleifera leaves extract can be used to treat periodontal diseases as a LDD agent.

Inclusion Complex of Ibuprofen-ß-Cyclodextrin Incorporated in Gel for Mucosal Delivery: Optimization Using an Experimental Design.

ß-Cyclodextrin/ibuprofen inclusion complex was synthesized by freeze-drying method and characterized for phase solubility profiles, infrared spectra, thermal analysis, and X-ray powder diffractograms. The inclusion complex with HP-ß-CD, as confirmed by molecular dynamics simulations, enhanced the aqueous solubility of ibuprofen by almost 30-fold compared to ibuprofen alone. Different grades of Carbopol (Carbopol 934P/Carbopol 974P/Carbopol 980 NF/Carbopol Ultrez 10 NF) and cellulose derivatives (HPMC K100M/HPMC K15M/HPMC K4M/HPMC E15LV/HPC) were evaluated for mucoadhesive gels incorporating the inclusion complex. The central composite design generated by Design-Expert was employed to optimize the mucoadhesive gel using two independent variables (a varying combination of two gelling agents) on three dependent variables (drug content and in vitro drug release at 6 h and 12 h). Except for the methylcellulose-based gels, most of the gels (0.5%, 0.75%, and 1% alone or as a mixture thereof) exhibited an extended-release of ibuprofen, ranging from 40 to 74% over 24 h and followed the Korsmeyer-Peppas kinetics model. Using this test design, 0.95% Carbopol 934P and 0.55% HPC-L formulations were optimized to increase ibuprofen release, enhance mucoadhesion, and be non-irritating in ex vivo chorioallantoic membrane studies. The present study successfully developed a mucoadhesive gel containing the ibuprofen-ß-cyclodextrin inclusion complex with sustained release.

Preparation and Characterization of Silymarin Gel: A Novel Topical Mucoadhesive Formulation for Potential Applicability in Oral Pathologies.

Silybum marianum has been used for centuries by herbalists and physicians to treat different forms of liver diseases. It contains flavonoid, which has antioxidant, anti-inflammatory, antifibrotic and anticancer properties. The objective of this research was to develop a silymarin-based mucoadhesive gel for prolonged release in oral mucosa and to evaluate the same by using in vitro drug release kinetic models and ex vivo methods for drug permeation using chicken buccal mucosa. The mucoadhesive gel was formulated in different trials by varying the concentration of silymarin and polymer. Out of 10 formulation trials, the F10 optimized trial was characterized for in vitro physicochemical parameters such as pH, homogeneity, viscosity, stability, drug content, in vitro drug release, in vitro antioxidant assay and ex vivo permeation study. Trial 10 was chosen as the best trial formulation among the other trials and was marked as an optimal trial. The physicochemical properties observed were pH to be 6.4 ± 0.01, the gel free of lumps, spreadability of 23.75 ± 0.03 and drug content of 32.77 ± 0.20 mg/g. It had no physiological changes such as color shift or fluid exudate segregation after 6 months of storage at room temperature. In vitro drug release established the presence of a non-fickian mechanism and demonstrated dose-dependent antioxidant activity. Ex vivo findings indicated 21.97 ± 0.18% release, proving that the gel can permeate through the oral mucosal membrane. Our future research will concentrate on expanding the therapeutic scope by developing the formulation trial F10 to a nanoformulation and conducting clinical trials for its potential use in various oral diseases.

Development of di(2-ethylhexyl) phthalate-containing thioglycolic acid immobilized chitosan mucoadhesive gel as an alternative hormone therapy for menopausal syndrome.

Menopausal syndrome includes the symptoms that most women experience owing to hormone changes after menopause. Although hormone replacement therapy is a common treatment for menopausal syndrome, there are still many side effects and challenges hindering research. In this study, thioglycolic acid (TGA)-immobilized chitosan mucoadhesive gel was synthesized by a new method of low concentration of 1,4-butanediol diglycidyl ether (BDDE) would encapsulate di(2-ethylhexyl) phthalate (DEHP) as an alternative hormone replacement therapy for menopausal syndrome. The efficacies of the DEHP-containing TGA-chitosan gel (CT-D) were confirmed and evaluated by materials characterization and in vitro study. Results showed that CT-D was not cytotoxic and had better mucoadhesive ability than chitosan. The animal model was constructed 1 month after bilateral ovariectomy in SD rats. CT-D was administered intravaginally every 3 days. Bodyweight, wet weight of the uterus and vagina, vaginal smears, histology, blood element analysis, and serological analysis was used to assess the ability of the material to relieve menopausal syndrome. The results indicated that the combination of the sustained release of DEHP and mucoadhesive TGA-immobilized chitosan allows the developed CT-D to relieve the menopausal syndrome through low concentrations of DEHP, which falls in the safety level of the tolerable daily intake of DEHP.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Intranasal Zolmitriptan-Loaded Bilosomes with Extended Nasal Mucociliary Transit Time for Direct Nose to Brain Delivery.

This study aimed at delivering intranasal zolmitriptan directly to the brain through preparation of bilosomes incorporated into a mucoadhesive in situ gel with extended nasal mucociliary transit time. Zolmitriptan-loaded bilosomes were constructed through a thin film hydration method applying Box-Behnken design. The independent variables were amount of sodium deoxycholate and the amount and molar ratio of cholesterol/Span® 40 mixture. Bilosomes were assessed for their entrapment efficiency, particle size and in vitro release. The optimal bilosomes were loaded into mucoadhesive in situ gel consisting of poloxamer 407 and hydroxypropyl methylcellulose. The systemic and brain kinetics of Zolmitriptan were evaluated in rats by comparing intranasal administration of prepared gel to an IV solution. Statistical analysis suggested an optimized bilosomal formulation composition of sodium deoxycholate (5 mg) with an amount and molar ratio of cholesterol/Span® 40 mixture of 255 mg and 1:7.7, respectively. The mucoadhesive in situ gel containing bilosomal formulation had a sol-gel temperature of 34.03 °C and an extended mucociliary transit time of 22.36 min. The gelling system possessed enhanced brain bioavailability compared to bilosomal dispersion (1176.98 vs. 835.77%, respectively) following intranasal administration. The gel revealed successful brain targeting with improved drug targeting efficiency and direct transport percentage indices. The intranasal delivery of mucoadhesive in situ gel containing zolmitriptan-loaded bilosomes offered direct nose-to-brain drug targeting with enhanced brain bioavailability.

Management of acute upper respiratory tract infection: the role of early intervention.

INTRODUCTION: Upper respiratory tract infection (URTI) is an illness caused by an acute infection by viruses or bacteria of the nose, sinuses, pharynx, and larynx. Most URTIs are short, mild, and self-limiting, but some can lead to serious complications, resulting in heavy social and economic burden on individuals and society. AREAS COVERED: This article presents the management guidelines and consensus established through the Delphi method during an expert roundtable conducted in November 2020 and results of a targeted literature review. EXPERT OPINION: The current acute URTI management strategies aim toward symptom alleviation and prevention of URTI virus transmission. The effectiveness of these strategies is highly increased with early intervention, administered prior to the peaking of viral shedding. This reduces the chances of developing a full-blown acute URTI, decreases symptom severity, and reduces viral transmission. Mucoadhesive gel nasal sprays have shown promising results for early intervention of acute URTI. They act by creating a barrier that can trap virus particles, thereby preventing invasion of the mucosa by the virus. Additionally, they deliver broad spectrum activity that is effective against a wide variety of pathogens that cause acute URTI. Acute URTI warrants greater attention and proactive management in reducing its burden.

Nanosized Transferosome-Based Intranasal In Situ Gel for Brain Targeting of Resveratrol: Formulation, Optimization, In Vitro Evaluation, and In Vivo Pharmacokinetic Study.

Resveratrol (RES) is a potent antioxidant used for the management of several central nervous system diseases. RES bioavailability is less than 1 owing to its low solubility and extensive intestinal and hepatic metabolism. The aim of the study was to enhance RES bioavailability through developing intranasal transferosomal mucoadhesive gel. Reverse evaporation-vortexing sonication method was employed to prepare RES-loaded transferosomes. Transferosomes were developed via 34 definitive screening design, using soya lecithin, permeation enhancers, and surfactants. The optimized formula displayed spherical shape with vesicle size of 83.79 ± 2.54 nm and entrapment efficiency (EE%) of 72.58 ± 4.51%. Mucoadhesive gels were prepared and evaluated, then optimized RES transferosomes were incorporated into the selected gel and characterized using FTIR spectroscopy, in vitro release, and ex vivo permeation study. Histopathological examination of nasal mucosa and in vivo pharmacokinetic study were conducted. In vitro drug release from transferosomal gel was 65.87 ± 2.12% and ex vivo permeation was 75.95 ± 3.19%. Histopathological study confirmed the safety of the optimized formula. The Cmax of RES in the optimized RES trans-gel was 2.15 times higher than the oral RES suspension and AUC(0-∞) increased by 22.5 times. The optimized RES trans-gel developed intranasal safety and bioavailability enhancement through passing hepatic and intestinal metabolism.

Local Formula with Mucoadhesive Property: A Randomized Clinical Trial of a Therapeutic Agent for the Treatment of Oral Aphthous Ulcers.

BACKGROUND: Recurrent or occasional aphthous lesions represent a painful oral condition with high prevalence. Since the etiology is still unclear and most likely related to a dysfunction in the local immune system, several treatment strategies have been proposed, including systemic agents, local agents, and laser therapy, to reduce the pain and discomfort for the patient without acting on the causes. MATERIALS AND METHODS: The purpose of the present randomized study was to assess the clinical efficacy of a new topical gel with mucoadhesive property to reduce the pain and the dimension of the aphthosis lesions. Fifty patients presenting at least one minor ulcer were randomized to a control group (placebo prescription), a first test group (topical agent with laser), and a second test group (topical agent only). The healing rate, the visual analog scale (VAS) score for pain, and the diameter reduction were monitored for 10 days. RESULTS: Both test groups showed better results than control group, significant clinical efficacy, and a median total reduction time of 4 days with no significant adjunctive benefit from the use of laser. CONCLUSION: The clinical results are encouraging; nevertheless other studies are needed to valid this kind of treatment. CLINICAL SIGNIFICANCE: The present randomized clinical study suggested that the use of topical mucoadhesive agents could represent a valid therapy for minor aphthous lesions. How to cite this article: Giammarinaro E, Cosola S, Oldoini G, et al. Local Formula with Mucoadhesive Property: A Randomized Clinical Trial of a Therapeutic Agent for the Treatment of Oral Aphthous Ulcers. J Contemp Dent Pract 2019;20(11):1249-1253.

Gemcitabine hydrochloride microspheres used for intravesical treatment of superficial bladder cancer: a comprehensive in vitro/ex vivo/in vivo evaluation.

INTRODUCTION: Bladder cancer is responsible for more than 130,000 deaths annually worldwide. Intravesical delivery of chemotherapeutic agents provides effective drug localization to the target area to reduce toxicity and increase efficacy. This study aimed to develop an intravesical delivery system of gemcitabine HCl (Gem-HCl) to provide a sustained-release profile, to prolong residence time, and to enhance its efficiency in the treatment of bladder cancer. MATERIALS AND METHODS: For this purpose, bioadhesive microspheres were successfully prepared with average particle size, encapsulation efficiency, and loading capacity of 98.4 µm, 82.657%±5.817%, and 12.501±0.881 mg, respectively. For intravesical administration, bioadhesive microspheres were dispersed in mucoadhesive chitosan or in situ poloxamer gels and characterized in terms of gelation temperature, viscosity, mechanical, syringeability, and bioadhesive and rheological properties. The cytotoxic effects of Gem-HCl solution, Gem-HCl microspheres, and Gem-HCl microsphere-loaded gel formulations were evaluated in two different bladder cancer cell lines: T24 (ATCC HTB4TM) and RT4 (ATCC HTB2TM). RESULTS: According to cell-culture studies, Gem-HCl microsphere-loaded poloxamer gel was more cytotoxic than Gem-HCl microsphere-loaded chitosan gel. Antitumor efficacy of newly developed formulations were investigated by in vivo studies using bladder-tumor-induced rats. CONCLUSION: According to in vivo studies, Gem-HCl microsphere-loaded poloxamer gel was found to be an effective and promising alternative for current intravesical delivery-system therapies.

Synthesis and Characterization of Thiolated PVP-Iodine Complexes: Key to Highly Mucoadhesive Antimicrobial Gels.

The aim of this study was to synthesize iodine containing polymeric excipients for mucosal treatment of microbial infection exhibiting a prolonged mucosal residence time by forming an adhesive gel on the mucosal surface. In order to achieve this aim, 2-(2 acryloylamino-ethyldisulfanyl)-nicotinic acid (ACENA) was copolymerized with N-vinylpyrrolidone (NVP) to obtain thiolated polyvinylpyrrolidone (PVP) for complexation with iodine. The average molecular mass of different thiolated PVP variants was determined by size exclusion chromatography. The structure of thiolated PVP was confirmed by 1H NMR. Thiolated PVP variants were characterized for thiol content, cytotoxicity, iodine loading capacity, rheological behavior, and adhesion time on mucosa. The highest achieved degree of thiolation was 610 ± 43 µmol/g, and the maximum recorded iodine loading was 949 ± 31 µmol/g of polymer. Thiolated PVP variants (0.5% m/v) showed no toxicity after incubation on Caco-2 cells for the period of 3 and 24 h, respectively. Thiolated PVP and thiolated PVP-iodine complexes exhibited a 5.4- and 4.4-fold increased dynamic viscosity in porcine mucus in comparison to PVP and PVP-iodine complex, respectively. Compared to PVP and PVP-iodine complex thiol-functionalized PVP and PVP-iodine complexes demonstrated significantly prolonged attachment to mucosal surface over a period of 3 h. Thiol functionalized PVP proved to be a promising novel excipient for complexation with iodine and to exhibit strongly improved mucoadhesive properties.

Topical oral wound healing potential of anthocyanin complex: animal and clinical studies.

AIM: An anthocyanin complex (AC), combined Zea mays and Clitoria ternatea extracts, was evaluated for topical oral wound healing in rats and a clinical trial in orthodontic patients. METHODS/RESULTS: AC enhanced anthocyanin permeation in vitro. In rats, 10% w/w of AC in a mucoadhesive gel (AG) reduced erythema and sizes of oral wounds after topical applications at higher extent than its placebo gel. Acute orthodontic wounds in 68 volunteers were randomly assigned to topically receive either AG or placebo gel and double-blind assessed. Wound size reduction and wound closure enhancement were obvious in AG-treated group on day 3 (p < 0.05). CONCLUSION: At 10% w/w, AC promoted wound closure and possessed a potential in healing stimulation of acute oral wounds.

Transmucosal delivery of melatonin-encapsulated niosomes in a mucoadhesive gel.

AIM: A transmucosal niosome gel was developed to improve the pharmacokinetics of exogenous melatonin. MATERIALS & METHODS: The melatonin niosomes (MN) gel was characterized and melatonin levels were determined in healthy volunteers. RESULTS: Micron-sized MN in a gel, mean ex vivo residence time of more than 3 h with maximum adhesiveness at 25 and 37°C showed similar in vitro release but different in vitro permeation to melatonin gel. Oral transmucosal MN gels, at 2.5, 5 and 10 mg, topically applied in 14 healthy volunteers in a randomized double-blinded crossover design with 7-day washout, gave dose-proportional pharmacokinetics, with improved absorption and prolonged systemic circulation. CONCLUSION: The transmucosal MN gel provides a topical option for melatonin administration with substantial prolonged systemic delivery.

Topical Niosome Gel Containing an Anthocyanin Complex: a Potential Oral Wound Healing in Rats.

Anthocyanins from dietary sources showing potential benefits as anti-inflammatory in oral lesions were developed as an anthocyanin complex (AC), comprised of extracts of Zea mays (CC) and Clitoria ternatea (CT), and formulated into a niosome gel to prove its topical oral wound healing in vitro and in vivo investigations. The AC formed nano-sized clusters of crystalline-like aggregates, occurring through both intra- and inter-molecular interactions, resulting in delivery depots of anthocyanins, following encapsulation in niosomes and incorporation into a mucoadhesive gel. In vitro permeation of anthocyanins was improved by complexation and further enhanced by encapsulation in niosomes. Collagen production in human gingival fibroblasts was promoted by AC and AC niosomes, but not CC or CT. The in vivo wound healing properties of AC gel (1 and 10%), AC niosome gel (1 and 10%), fluocinolone acetonide gel, and placebo gel were investigated for incisional wounds in the buccal cavities of Wistar rats. AC gel and AC niosome gel both reduced wound sizes after 3 days. AC niosome gel (10%) gave the highest reduction in wound sizes after day 3 (compared to fluocinolone acetonide gel, p < 0.05), and resulted in 100% wound healing by day 5. Histological observations of cross-sectioned wound tissues revealed the adverse effects of fluocinolone gel and wound healing potential of AC niosome gel. Topical application of AC niosome gel exhibited an anti-inflammatory effect and promoted oral wound closure in rats, possibly due to the improved mucosal permeability and presence of delivery depots of AC in the niosome gel.

Efficacy of grape seed extract gel in the treatment of chronic periodontitis: A randomized clinical study.

AIM: The aim of the present study was to assess the effectiveness of applying grape seed extract (GSE) gel in periodontal pockets for the treatment of chronic periodontitis. METHODS: Eighty-six sites with pocket depth (PD) >4 mm were selected from five systemically-healthy patients in whom scaling, and root planing were performed, and oral instructions were given, a week earlier. PD, gingival index (GI), plaque index (PI), and bleeding on probing (BOP) were measured, and sites were then divided into the control group (N = 38) and GSE group (N = 48). Four doses of formulated 2% mucoadhesive GSE gel were applied to GSE group sites at baseline visit (T0), and 3, 6, and 9 days after T0. Similarly, a control gel was applied to the control sites. PD, PI, GI and BOP were re-evaluated after 4 weeks and 6 months of first gel application. RESULTS: Paired t test for both the control and GSE groups showed a significant reduction for all variables after 6 months of gel application (P < .05). The independent t test showed a significant difference (P < .05) only in the reduction of gingival index (mean: 0.85 ± 0.77 for control and 1.3 ± 0.8 for GSE) and plaque index (mean: 0.75 ± 0.71 for control and 1.12 ± 0.7 for GSE). CONCLUSION: The subgingival application of the formulated 2% mucoadhesive GSE gel showed significant improvement in the PI and GI only.

Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: preparation, characterization and application in a vaginal drug delivery system.

Lack of mucoadhesive properties is the major drawback to poloxamer 407 (F127)-based in situ hydrogels for mucosal administration. The objective of the present study was to construct a novel mucoadhesive and thermosensitive in situ hydrogel drug delivery system based on an amino-functionalized poloxamer for vaginal administration. First, amino-functionalized poloxamer 407 (F127-NH2) was synthesized and characterized with respect to its micellization behavior and interaction with mucin. Then using acetate gossypol (AG) as model drug, AG-loaded F127-NH2-based in situ hydrogels (NFGs) were evaluated with respect to rheology, drug release, ex vivo vaginal mucosal adhesion, in vivo intravaginal retention and local irritation after vaginal administration to healthy female mice. The results show that F127-NH2 is capable of forming a thermosensitive in situ hydrogel with sustained drug release properties. An interaction between positively charged F127-NH2 and negatively charged mucin was revealed by changes in the particle size and zeta potential of mucin particles as well as an increase in the complex modulus of NFG caused by mucin. Ex vivo and in vivo fluorescence imaging and quantitative analysis of the amount of AG remaining in mouse vaginal lavage all demonstrated greater intravaginal retention of NFG than that of an unmodified F127-based in situ hydrogel. In conclusion, amino group functionalization confers valuable mucoadhesive properties on poloxamer 407.