Acitretin and treatment of the oral leucoplakias. A model to have an active molecules release

AIMS: The aim of this study was to investigate the effectiveness of acitretin in a new topical formulation (mucoadhesive two-layer tablets) for the treatment of oral leucoplakias. METHODS: Twenty-one volunteers, 16 men, five women, with oral leucoplakia (histologically diagnosed), were included in this double-blind placebo-controlled study. Patients were randomized in three groups (A, B, C) of seven patients each. Groups A and B received tablets with different in vitro release profiles, and group C subjects (controls) received tablets without acitretin. The acitretin dose was 20 mg/day (two 10 mg tablets daily). Serum aspartate aminotransferase, alanine aminotransferase, cholesterol and triglycerides were evaluated before and after treatment. At the end of therapy the concentrations of acitretin in plasma, saliva and tissue were measured by high-performance liquid chromatography. RESULTS: At the end of the study 71% (groups A and B) of patients showed clinical remission or marked improvement. No improvement was noted in the control subjects (group C). These results were further confirmed by histological findings. There were no significant changes in laboratory values in the three groups. The acitretin concentration in plasma and tissue ranged from 0 to 50 mg with no difference between groups A and B, and it was very high in saliva (ranging from 4.9 to 43 mg) with higher concentrations in group A than in group B (due to a longer adhesion time in group A). Patients' compliance was excellent. The results show that mucoadhesive tablets of topical acitretin are efficacious in the treatment of oral leucoplakia without systemic side-effects.     

Nanoemulsion based Intranasal Delivery of Antimigraine Drugs for Nose to Brain Targeting

The objective of this study was to develop intranasal nanoemulsion and gel formulations for rizatriptan benzoate for prolonged action. Nanoemulsion formulations were prepared by constructing pseudo-ternary phase diagrams using lipophilic and hydrophilic surfactants and water. Various mucoadhesive agents were tried out to form thermo-triggered mucoadhesive nanoemulsions. Mucoadhesive gel formulations of rizatriptan were prepared using different ratios of HPMC and Carbopol 980. Comparative evaluation of intranasal nanoemulsions and intranasal mucoadhesive gels indicated that greater brain-targeting could be achieved with nanoemulsions.     

Mucoadhesive Hybrid Polymer/Liposome Pastes Based on Modified Polysaccharides

Mucoadhesive hybrid polymer/liposome paste is a new drug delivery system presenting controllable and tailorable delivery mechanism. By using mucoadhesive material, the delivery can be more specific and local. Here, we present a study investigating the effect of polymer type, concentration, functional end group, and cross-linking on the release profile of nanoliposomes from polymer pastes. Polymer pastes can be expected to combine the mucoadhesion mechanisms of dry and wet dosage forms but have not been studied extensively. To better understand the mucoadhesion of pastes, we investigated a series of pastes based on the same polymer and used different chemical modifications that can produce interactions at different levels. Native and thiolated polymers presented enhanced mucoadhesion in a wet environment in comparison to acrylated polymers which dissolved rapidly because of the enhanced solubility of PEG chains in water. Paste cross-linking resulted in a sustained release profile compared to non–cross-linked pastes. Pectin-SH pastes, especially 3% (w/v), showed a linear liposomal release profile which is ascribed to the combination of ionic cross-linking and disulfide bridging. By configuring the polymer type or concentration, we can control the release mechanisms and achieve distinct inherent properties which can be applied for diverse medical applications.     

Preparation and characterization of bioadhesive controlled-release gels of cidofovir for vaginal delivery

The aim of this study was to develop mucoadhesive and thermosensitive gels for vaginal delivery that would be able to provide a controlled release of the model drug, cidofovir. The study also monitored the drug’s potential antiviral properties. Cidofovir was put into the form of a vaginal gel, using mucoadhesive and thermosensitive polymers such as chitosan, Carbopol 974P, HPMC, and poloxamer 407. The physicopharmaceutical properties and stability of the vaginal gel formulations were evaluated. The gel formulation which was prepared with HPMC K100M exhibited the highest viscosity, as well as maximum adhesiveness, cohesiveness, and mucoadhesion values. The results of antiviral activity studies, which used the bovine herpes virus type 1 virus infection in vitro model using Vero cells, demonstrated the antiherpetic effect of the cidofovir gel containing HPMC K100M, at least under in vitro conditions. The study found that a mucoadhesive vaginal gel containing cidofovir can be a promising and innovative alternative therapeutic system for the treatment of genital herpes simplex virus and human papilloma virus induced infections in women.     

Mucoadhesive poly(vinyl alcohol) hydrogels produced by freezing/thawing processes: Applications in the development of wound healing systems

Ultrapure poly(vinyl alcohol) (PVA) hydrogels were prepared by exposing an aqueous solution of 15 or 20 wt% PVA to repeated cycles of freezing for 6 or 12 h at -20°C and thawing for 2 hours at 25°C. The adhesive characteristics of the PVA gels in contact with a reconstituted mucus surface were quantified using a tensile technique. As the number of freezing/thawing cycles increased, the work of fracture (adhesion) decreased due to the increase in the PVA degree of crystallinity. Crystallinity was determined using differential scanning calorimetry. PVA gels prepared from the 20 wt% solution and exposed to two cycles of freezing/ thawing exhibited the largest work of adhesion. Drug delivery studies were conducted with ketanserin, a wound healing enhancer. Release studies were conducted using PVA samples prepared from a 20-wt% solution that were exposed to two or three freezing cycles for 12 h followed by thawing for 2 h. Results from the release of the drug from the PVA sample exposed to two cycles showed that approximately 80% of the ketanserin was released within 4 h.     

Curcumin-containing chitosan nanoparticles as a potential mucoadhesive delivery system to the colon

In the present study, we investigate the mucoadhesive characteristics and release of the anticancer agent curcumin, contained in chitosan nanoparticles (CS-NPs). Such a system has potential therapeutic benefits in the treatment of colon cancer through prolonged retention and delivery. The CS-NPs were ionically gelled with tripolyphosphate (TPP) and registered an isoelectric pH of 6.2 (z-average diameter of 214?nm ± 1.0?nm). pH variations around the isoelectric point caused a reduction in CS-NPs electrical charge which correspondingly increased the z-average due to agglomeration. Curcumin release from CS-NPs was slowest at chitosan to TPP weight ratio of 3:1, with a significant retention (36%) at the end of 6?h. Adsorption isotherms of mucin on CS-NPs fitted both the Freundlich and Langmuir models, suggesting a monolayer-limited adsorption on heterogeneous sites with varied affinities. Encapsulated curcumin exerted an influence on the adsorption of mucin due to H-bonding as well as π-π interactions between the phenolic moieties of curcumin and mucin.     

Use of a mucoadhesive disk for relief of dry mouth: a randomized, double-masked, controlled crossover study

BackgroundDry mouth is a frequent complaint of adults worldwide. In those who experience dry mouth, therapeutic options include the use of salivary substitutes and sialogogues.MethodsThe authors compared the efficacy and safety of mucoadhesive disks (OraMoist, Axiomedic, Zurich; distributed by Quantum Health, Eugene, Ore.) applied three times daily with those of placebo mucoadhesive disks in a double-masked, randomized, controlled crossover study. The primary end point of interest was within-participant differences in subjective (visual analog scale) ratings of dry mouth according to the New York University Bluestone Mouthfeel Questionnaire. The secondary end point was within-participant differences in salivary flow rates.ResultsTwenty-seven participants completed the single-site study. The results showed no significant difference between the two types of mucoadhesive disks, both of which were associated with a statistically significant improvement in the subjective experience of moistness across the 60-minute period after application and compared with baseline measures after two weeks of use. Furthermore, both disks were associated with a statistically significant improvement in salivary flow rates across the 60-minute period after application and compared with baseline measures after one and two weeks of use. The disks were well tolerated, and participants did not report any adverse events.ConclusionsThe mucoadhesive disks used in this study were safe and provided symptomatic relief from dry mouth.Practice ImplicationsPatients with dry mouth may benefit from this novel delivery system.