Evaluation of the impact of tragacanth/xanthan gum interpolymer complexation with chitosan on pharmaceutical performance of gels with secnidazole as potential periodontal treatment.

Periodontitis consists a group of dental disorders that affect about 70 % of the world population. The therapy mainly relies on mechanical removing bacterial biofilm, nevertheless, local or systemic antibacterial agents play a key role in treating the acute conditions. Secnidazole is a newer derivative of commonly used metronidazole with high safety profile and broad spectrum of antimicrobial activity. The aim of the study was to evaluate the applicability of polyelectrolyte complex-based hydrogels composed of anionic tragacanth with addition of xanthan gum and cationic chitosan as carriers for buccal/intra pocket delivery of secnidazole. Prepared hydrogels with 5 % and 10 % (w/w) drug content were evaluated pharmaceutically towards inter alia physicomechanical, rheological and thermal properties, drug release kinetics, swelling behavior or antimicrobial activity. Cytotoxicity against human primary umbilical vein endothelial cells was also assessed with two independent method. Stable compositions with secnidazole were obtained, however, various miscibility of the drug with the polymers was noted. By adding chitosan, antibacterial activity and swelling performance of the gels were improved, nevertheless, drop of the mucoadhesiveness was also recorded. Hydrogels with 5 % secnidazole were selected as effective antimicrobial compositions with the highest cytocompatibility. They might be considered as promising for oromucosal application with special attention given to SEC as an alternative locally administered antimicrobial agent.

Preliminary Assessment of Polysaccharide-Based Emulgels Containing Delta-Aminolevulinic Acid for Oral Lichen planus Treatment.

Photodynamic therapy using delta-aminolevulinic acid is considered a promising option in the treatment of oral lichen planus. In the present work, three emulgel compositions prepared from natural polysaccharide gums, tragacanth, xanthan and gellan, were preliminarily tested for oromucosal delivery of delta-aminolevulinic acid. Apart from cytotoxicity studies in two gingival cell lines, the precise goal was to investigate whether the presence of the drug altered the rheological and mucoadhesive behavior of applied gelling agents and to examine how dilution with saliva fluid influenced the retention of the designed emulgels by oromucosal tissue. Ex vivo mucoadhesive studies revealed that a combination of xanthan and gellan gum enhanced carrier retention by buccal tissue even upon dilution with the saliva. In turn, the incorporation of delta-aminolevulinic acid favored interactions with mucosal tissue, particularly formulations comprised of tragacanth. The designed preparations had no significant impact on the cell viability after a 24 h incubation in the tested concentration range. Cytotoxicity studies demonstrated that tragacanth-based and gellan/xanthan-based emulgels might exert a protective effect on the metabolic activity of human gingival fibroblasts and keratinocytes. Overall, the presented data show the potential of designed emulgels as oromucosal platforms for delta-aminolevulinic acid delivery.

Evaluation of Oromucosal Natural Gum-Based Emulgels as Novel Strategy for Photodynamic Therapy of Oral Premalignant Lesions.

Photodynamic therapy (PDT) recently has been shown as a promising option in the treatment of premalignant lesions of the soft oral tissues. Effective delivery of photosensitizer is challenging due to poor drug adherence to the oromucosal epithelium. In the present work, emulgels composed of natural polysaccharide gums (tragacanth, xanthan and gellan) were evaluated as novel oromucosal platforms of delta-aminolevulinic acid (ALA) for PDT. Apart from mucoadhesive and textural analysis, the specific steps involved studies on drug penetration behavior and safety profile using a three-dimensional human oral epithelium model (HOE). All designed emulgels presented greater mucoadhesiveness when compared to commercial oromucosal gel. Incorporation of ALA affected textural properties of emulgels, and tragacanth/xanthan formulation with greater hardness and cohesiveness exhibited a protective function against the mechanical tongue stress. Permeability studies revealed that ALA is capable of penetrating across oromucosal epithelium by passive transport and all formulations promoted its absorption rate when compared to a commercial topical product with ALA. Importantly, the combination of tragacanth and xanthan profoundly enhanced photosensitizer retention in the buccal epithelium. Tested samples performed negligible reduction in cell viability and moderately low IL-1ß release, confirming their non-irritancy and compatibility with HOE. Overall, the presented findings indicate that tragacanth/xanthan emulgel holds promise as an oromucosal ALA-carrier for PDT strategy.

Optimization of Multilayer Films Composed of Chitosan and Low-Methoxy Amidated Pectin as Multifunctional Biomaterials for Drug Delivery.

Polyelectrolyte multilayers (PEMs) based on polyelectrolyte complex (PEC) structures are recognized as interesting materials for manufacturing functionalized coatings or drug delivery platforms. Difficulties in homogeneous PEC system development generated the idea of chitosan (CS)/low-methoxy amidated pectin (LM PC) multilayer film optimization with regard to the selected variables: the polymer ratio, PC type, and order of polymer mixing. Films were formulated by solvent casting method and then tested to characterize CS/LM PC PECs, using thermal analysis, Fourier transform infrared spectroscopy (FTIR), turbidity, and zeta potential measurements. The internal structure of the films was visualized by using scanning electron microscopy. Analysis of the mechanical and swelling properties enabled us to select the most promising formulations with high uniformity and mechanical strength. Films with confirmed multilayer architecture were indicated as a promising material for the multifunctional systems development for buccal drug delivery. They were also characterized by improved thermal stability as compared to the single polymers and their physical mixtures, most probably as a result of the CS-LM PC interactions. This also might indicate the potential protective effect on the active substances being incorporated in the PEC-based films.

The Potential of Polyelectrolyte Multilayer Films as Drug Delivery Materials.

Polyelectrolyte multilayers (PEMs) represent a group of polyelectrolyte complex (PEC)-based materials widely investigated in the biomedical and pharmaceutical sciences. Despite the unflagging popularity of the aforementioned systems in tissue engineering, only a few updated scientific reports concerning PEM potential in drug administration can be found. In fact, PEM coatings are currently recognized as important tools for functionalizing implantable scaffolds; however, only a small amount of attention has been given to PEMs as drug delivery materials. Scientific reports on PEMs reveal two dominant reasons for the limited usability of multilayers in pharmaceutical technology: complex and expensive preparation techniques as well as high sensitivity of interacting polyelectrolytes to the varieties of internal and external factors. The aim of this work was to analyze the latest approaches, concerning the potential of PEMs in pharmacy, chemical technology, and (primarily) tissue engineering, with special attention given to possible polymer combinations, technological parameters, and physicochemical characteristics, such as hydrophilicity, adhesive and swelling properties, and internal/external structures of the systems formed. Careful recognition of the above factors is crucial in the development of PEM-based drug delivery materials.

Multilayer Films Based on Chitosan/Pectin Polyelectrolyte Complexes as Novel Platforms for Buccal Administration of Clotrimazole.

Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with good retentivity at the mucosa intended for the therapy of oromucosal conditions, especially infectious diseases. Multilayer films composed of layers of oppositely charged polymers separated by ionically interacting polymeric chains creating polyelectrolyte complexes represent very interesting and relatively poorly explored area. We aimed to develop the antifungal multilayer systems composed of cationic chitosan and anionic pectin as potential platforms for controlled delivery of clotrimazole. The systems were pharmaceutically characterized with regard to inter alia their release kinetics under different pH conditions, physicomechanical, or mucoadhesion properties with using an animal model of the buccal mucosa. The antifungal activity against selected Candida sp. and potential cytotoxicity with regard to human gingival fibroblasts were also evaluated. Interactions between polyions were characterized with Fourier transform infrared spectroscopy. Different clotrimazole distribution in the films layers highly affected their in vitro dissolution profile. The designed films were recognized as intelligent pH-responsive systems with strong antifungal effect and satisfactory safety profile. As addition of chitosan resulted in the improved antifungal behavior of the drug, the potential utilization of the films in resistant cases of oral candidiasis might be worth of further exploration.

Tragacanth Gum/Chitosan Polyelectrolyte Complexes-Based Hydrogels Enriched with Xanthan Gum as Promising Materials for Buccal Application.

Polyelectrolyte complexes based on the electrostatic interactions between the polymers mixed are of increasing importance, therefore, the aim of this study was to develop hydrogels composed of anionic tragacanth gum and cationic chitosan with or without the addition of anionic xanthan gum as carriers for buccal drug delivery. Besides the routine quality tests evaluating the hydrogel's applicability on the buccal mucosa, different methods directed toward the assessment of the interpolymer complexation process (e.g., turbidity or zeta potential analysis, scanning electron microscopy and Fourier-transform infrared spectroscopy) were employed. The addition of xanthan gum resulted in stronger complexation of chitosan that affected the hydrogel's characteristics. The formation of a more viscous PEC hydrogel with improved mucoadhesiveness and mechanical strength points out the potential of such polymer combination in the development of buccal drug dosage forms.

The Correlation between Physical Crosslinking and Water-Soluble Drug Release from Chitosan-Based Microparticles.

Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan glutamate and beta-glycerophosphate as an ion crosslinker (CF). The Box-Behnken design was applied to optimize the microparticles in terms of their drug loading and release behavior. Physicochemical studies were undertaken to support the results from dissolution tests and to evaluate the impact of the crosslinking ratio on the microparticles' characteristics. The zidovudine dissolution behavior had a complex nature which comprised two phases: an initial burst effect followed with a prolonged release stage. The initial drug release, which can be modulated by the crosslinking degree, was primarily governed by the dissolution of the drug crystals located on the microparticles' surfaces. In turn, the further dissolution stage was related to the drug diffusion from the swollen polymer matrix and was found to correlate with the drug loading. Differential Scanning Calorimetry (DSC) studies revealed the partial incorporation of a non-crystallized drug within the polymer matrix, which correlated with the amount of CF. Although CF influenced the swelling capacity of chitosan glutamate microparticles, surprisingly a higher amount of CF did not impact the time required for 80% of the drug to be released markedly. The formulation with the lowest polymer:CF ratio, 3:1, was selected as optimal, providing satisfactory drug loading and displaying a moderate burst effect within the first 30 min of the study, followed with a prolonged drug release of up to 210 min.

Development, characterisation and nasal deposition of melatonin-loaded pectin/hypromellose microspheres.

In this study, we present the development of spray-dried pectin/hypromellose microspheres as efficient melatonin carrier for targeted nasal delivery. Different pectin to hypromellose weight ratios in the spray-dried feed were employed (i.e. 1:0, 3:1, 1:1 and 1:3) in order to optimise microsphere physicochemical properties influencing overall powder behaviour prior, during and upon nasal delivery. All microspheres assured complete melatonin entrapment and increased dissolution rate in relation to pure melatonin powder. Among all combinations tested, combining pectin with hypromellose at 1:3 wt ratio resulted in the microspheres with the highest potential for melatonin nasal delivery as they assured highest swelling ability and most prominent mucoadhesive properties. Studies on deposition profile revealed adequate turbinate and olfactory deposition of microsphere/lactose monohydrate powder blend administered nasally using MIAT® device, complementing findings relevant for their therapeutic potential. In conclusion, developed microspheres bear the potential to ensure prolonged melatonin retention at the nasal mucosa, improved bioavailability and advanced therapeutic outcome.