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.

Mucoadhesive Alginate/Pectin Films Crosslinked by Calcium Carbonate as Carriers of a Model Antifungal Drug-Posaconazole.

The mucosal membrane of the oral cavity, due to its unique structure and availability, constitutes an appropriate site for the delivery of drugs, both with local and systemic effects. Mucoadhesive buccal films are drug dosage forms that due to their convenience of application, flexibility and size, are characterized by patients' compliance. Sodium alginate and pectin are natural polymers from the polysaccharides group, with mucoadhesive properties, that are widely applied to obtain buccal films. However, their hydrophilic nature and poor water resistance limit their application in sustained drug release formulations. Hence, the aim of this investigation was to design alginate/pectin buccal films by a one-step crosslinking technique-with the application of calcium carbonate. This technique was applied to prepare crosslinked alginate and alginate/pectin mucoadhesive films with a model antifungal drug-posaconazole. The obtained formulations were evaluated for the impact of crosslinking and pectin's presence on their pharmaceutical, mucoadhesive, mechanical and physicochemical properties. Additionally, the antifungal activity of the prepared films against Candida spp. was evaluated. It was shown that pectin's presence in the formulations improved flexibility, mucoadhesion and antifungal activity. The crosslinking process reduced mucoadhesiveness and antifungal activity but significantly enhanced the mechanical properties and stability and enabled prolonged drug release.

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.

The Impact of Hypromellose on Pharmaceutical Properties of Alginate Microparticles as Novel Drug Carriers for Posaconazole.

Fungal infections are a group of diseases which are challenging to treat because of drug-resistant fungi species, drug toxicity, and often severe patient conditions. Hence, research into new treatments, including new therapeutic substances and novel drug delivery systems, is being performed. Mucoadhesive dosage forms are beneficial to improving drug bioavailability by prolonging the residence time at the site of application. Sodium alginate is a natural polymer with favorable mucoadhesive and gelling properties, although its precipitation in acidic pH significantly disrupts the process of drug release in gastric conditions. Hypromellose is a hydrophilic, semi-synthetic cellulose derivative with mucoadhesive properties, which is widely used as a control release agent in pharmaceutical technology. The aim of this study was to evaluate the impact of hypromellose on alginate microparticles with posaconazole, designed to modify drug release and to improve their mucoadhesive properties for both oral or vaginal application.

The Spray-Dried Alginate/Gelatin Microparticles with Luliconazole as Mucoadhesive Drug Delivery System.

Candida species are opportunistic fungi, which are primary causative agents of vulvovaginal candidiasis. The cure of candidiasis is difficult, lengthy, and associated with the fungi resistivity. Therefore, the research for novel active substances and unconventional drug delivery systems providing effective and safe treatment is still an active subject. Microparticles, as multicompartment dosage forms due to larger areas, provide short passage of drug diffusion, which might improve drug therapeutic efficiency. Sodium alginate is a natural polymer from a polysaccharide group, possessing swelling, mucoadhesive, and gelling properties. Gelatin A is a natural high-molecular-weight polypeptide obtained from porcine collagen. The purpose of this study was to prepare microparticles by the spray-drying of alginate/gelatin polyelectrolyte complex mixture, with a novel antifungal drug-luliconazole. In the next stage of research, the effect of gelatin presence on pharmaceutical properties of designed formulations was assessed. Interrelations among polymers were evaluated with thermal analysis and Fourier transform infrared spectroscopy. A valid aspect of this research was the in vitro antifungal activity estimation of designed microparticles using Candida species: C. albicans, C. krusei, and C. parapsilosis. It was shown that the gelatin addition affected the particles size, improved encapsulation efficiency and mucoadhesiveness, and prolonged the drug release. Moreover, gelatin addition to the formulations improved the antifungal effect against Candida species.

Chitosan-poly(ethylene oxide) nanofibrous mat as a vaginal platform for tenofovir disoproxyl fumarate - The effect of vaginal pH on drug carrier performance.

In the present work, a solution blow spun nanofibrous mat comprised of chitosan (CS) and poly(ethylene oxide) (PEO) was obtained as vaginal platform for tenofovir disoproxil fumarate (TDF) to prevent sexually transmitted infections. Apart from physicochemical and mechanical analysis, the specific steps involved studies on nanofibrous mat mucoadhesive and swelling characteristics upon pH fluctuations over the physiological range. Physicochemical analysis showed uniform drug distribution within the CS/PEO mat volume and pointed toward physical interactions between the drug and polymers. TDF-loaded CS/PEO nanofibrous mat was shown potentially safe when evaluated by the MTT metabolic activity and JC-1 assays in human vaginal epithelial cells VK2-E6/E7. In vitro antiviral studies indicated inhibition efficacy of TDF-CS/PEO nanofibrous mat toward HSV-2 virus and proved the SBS process does not change the microbicidal activity of drug molecule. Fluctuations in the physiological vaginal pH range of 3.8 to 5.0 substantially affected mucoadhesive and swelling behavior of chitosan which in turn impacted drug dissolution rate from polymer carrier. The rate of permeation and accumulation of TDF in vaginal tissue differed in response to vaginal pH. Faster drug permeation assessed at pH 5.0 suggests that an increase in vaginal pH could improve TDF bioavailability at earlier time points.

Incorporation of Ethylcellulose Microparticles Containing a Model Drug with a Bitter Taste into Nanofibrous Mats by the Electrospinning Technique-Preliminary Studies.

Electrospinning is considered a simple and comprehensive technique to formulate ultrafine fibres by using an electric field. Polymeric nanofibers constitute promising materials in biomedical applications as drug delivery systems. For their preparation, both natural and synthetic polymers are utilised. Owing to the potential use of electrospun nanofibers as an orodispersible drug dosage form, ethylcellulose microparticles containing the antihistamine drug rupatadine fumarate, prepared by the spray drying technique to conceal the drug's bitter taste, were incorporated into nanofibers. The obtained nanofibrous mats were evaluated for morphology, mechanical strength, disintegration time, the drug solid state and acceptability in terms of taste masking efficiency. Preliminary studies showed that hypromellose used as a single polymer was not a suitable substance for the manufacturing of nanofibers. Therefore, in order to facilitate the obtention of homogeneous nonwovens, different grades of polyethylene oxide (2,000,000-2M-Da and 4,000,000-4M-Da) were added, which improved the quality of the prepared mats. Nanofibers of the most satisfactory quality were obtained from hypromellose (6.5% w/v) and PEO (2M, 0.5% w/v). SEM image analysis has shown that the nanofibers were homogeneous and smooth and possessed a fast disintegration time (below 30 s) and an adequate drug content with a simultaneous taste-masking effect (as indicated by the in vivo and in vitro methods). However, further studies are necessary to refine their mechanical characteristics.

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.

Does the Freeze-Thaw Technique Affect the Properties of the Alginate/Chitosan Glutamate Gels with Posaconazole as a Model Antifungal Drug?

Hydrogels are semi-solid systems with high flexibility, which, due to holding large amounts of water, are similar to natural tissues and are very useful in the field of biomedical applications. Despite the wide range of polymers available to form hydrogels, novel techniques utilized to obtain hydrogels with adequate properties are still being developed. The aim of this study was to evaluate the impact of the freeze-thaw technique on the properties of cryogels based on sodium alginate and chitosan glutamate with posaconazole as a model antifungal substance. The effect of the freezing and thawing process on the physicochemical, rheological, textural and bioadhesive properties of prepared cryogels was examined. Additionally, the antifungal activity against Candida albicans, Candida parapsilosis and Candida krusei of designed formulations was examined. It was shown that the freeze-thaw technique significantly improved viscosity, bioadhesiveness, textural properties and prolonged the in vitro posaconazole release. Moreover, alginate/chitosan glutamate cryogels exhibited higher values of inhibition zone in C. parapsilosis culture than traditional hydrogel formulations.

Chitosan-Enriched Solution Blow Spun Poly(Ethylene Oxide) Nanofibers with Poly(Dimethylsiloxane) Hydrophobic Outer Layer for Skin Healing and Regeneration.

Chitosan (CS)/poly(ethylene oxide) (PEO)-based nanofiber mats have attracted particular attention as advanced materials for medical and pharmaceutical applications. In the scope of present studies, solution blow spinning was applied to produce nanofibers from PEO and CS and physicochemical and biopharmaceutical studies were carried out to investigate their potential as wound nanomaterial for skin healing and regeneration. Additional coating with hydrophobic poly(dimethylsiloxane) was applied to favor removal of nanofibers from the wound surface. Unmodified nanofibers displayed highly porous structure with the presence of uniform, randomly aligned nanofibers, in contrast to coated materials in which almost all the free spaces were filled in with poly(dimethylsiloxane). Infrared spectroscopy indicated that solution blow technique did not influence the molecular nature of native polymers. Obtained nanofibers exhibited sufficient wound exudate absorbency, which appears beneficial to moisturize the wound bed during the healing process. Formulations displayed greater tensile strength as compared to commercial hydrofiber-like dressing materials comprised of carboxymethylcellulose sodium or calcium alginate, which points toward their protective function against mechanical stress. Coating with hydrophobic poly(dimethylsiloxane) (applied to favor nanofiber removal from the wound surface) impacted porosity and decreased both mechanical properties and adherence to excised human skin, though the obtained values were comparable to those attained for commercial hydrofiber-like materials. In vitro cytotoxicity and irritancy studies showed biocompatibility and no skin irritant response of nanofibers in contact with a reconstituted three-dimensional human skin model, while scratch assay using human fibroblast cell line HDFa revealed the valuable potential of CS/PEO nanofibers to promote cell migration at an early stage of injury.

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.

Orodispersible Films with Rupatadine Fumarate Enclosed in Ethylcellulose Microparticles as Drug Delivery Platform with Taste-Masking Effect.

Orally disintegrating (orodispersible) films provide a versatile tool for drug administration, especially in the pediatric and geriatric population, since they reduce the risk of choking and do not necessitate drinking water during application. By considering their direct contact with the taste buds, palatability is an influential aspect related to patient compliance. The microparticles based on taste-masking polymers containing drugs enclosed inside effectively mask the unpleasant taste of medicines. Ethylcellulose is a hydrophobic polymer widely used as a taste-masking material. Rupatadine fumarate, a second-generation antihistamine drug, is characterised by an intense bitter taste; therefore, it is crucial to achieve a tolerable taste whilst developing orodispersible formulations with its content. The objective of this study was to develop orally disintegrating films with rupatadine fumarate in the form of ethylcellulose-based microparticles obtained from aqueous dispersions of ethylcellulose-Surelease® or Aquacoat® ECD. It was a technological challenge to achieve homogenous drug content per dosage unit and sufficient mechanical properties for film operating due to the necessity to suspend the microparticles in the casting solution. Although the process of obtaining films consisted of several steps (mixing, pouring, drying), the particles were homogeneously dispersed, and each film of the desired size contained the proper dose of the drug. The taste-masking effect was also maintained. This parameter was confirmed by three independent methods: in vivo by healthy volunteers, an electronic tongue and a dissolution test. The applied taste-evaluation techniques showed that the films containing Aquacoat® ECD microparticles have the highest degree of bitter taste reduction, which confirms the results obtained in our previous studies.

Nanostructured Lipid Carriers (NLC)-Based Gel Formulations as Etodolac Delivery: From Gel Preparation to Permeation Study.

Topical administration of drug is an attractive alternative to the oral administration as it provides a reduction in adverse reactions and an enhancement of therapeutic effects. The use of lipid carriers in hydrogel structures makes it possible to introduce lipophilic substances in a dissolved form. In this study, an NSAID from the BCS class II, etodolac (ETD), was used. The nanostructured lipid carriers (NLC) obtained with ETD were incorporated into semi-solid forms (gels). Hydrogels with the suspended drug and oleogel were also prepared for comparison purposes. The obtained gels were tested in terms of pH, viscosity, rheological, mechanical, and bioadhesive properties. The release and permeation through membranes were also studied. All tested formulations were characterized by a pH below 7, which ensured the physiological state of the skin. The viscosities of all gels decreased with increasing shear rate, indicating non-Newtonian behavior. The fastest ETD release was observed for NLC with a Carbopol base (formulation F1); a similar result was noticed in the permeation test. The developed gel formulations containing ETD-NLC dispersion and Carbopol or Poloxamer as gelling agents were stable and possessed beneficial pharmaceutical properties.

Alginates Combined with Natural Polymers as Valuable Drug Delivery Platforms.

Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or anti-inflammatory activities. ALG are characterized by gelling ability, one of the most frequently utilized properties in the drug form design. ALG have numerous applications in pharmaceutical technology that include micro- and nanoparticles, tablets, mucoadhesive dosage forms, wound dressings and films. However, there are some shortcomings, which impede the development of modified-release dosage forms or formulations with adequate mechanical strength based on pure ALG. Other natural polymers combined with ALG create great potential as drug carriers, improving limitations of ALG matrices. Therefore, in this paper, ALG blends with pectins, chitosan, gelatin, and carrageenans were critically reviewed.

Development and Evaluation of Thermosensitive Hydrogels with Binary Mixture of Scutellariae baicalensis radix Extract and Chitosan for Periodontal Diseases Treatment.

Scutellaria baicalensis root displays anti-inflammatory and antibacterial properties due to the presence of flavonoids, particularly baicalin, baicalein, and wogonin. Our work aimed at developing thermosensitive hydrogels containing a binary mixture of S. baicalensis radix lyophilized extract and chitosan as a novel approach for periodontal diseases treatment. Two types of chitosan were employed in preliminary studies on binary mixtures with S. baicalensis radix lyophilized extract standardized for baicalin, baicalein, and wogonin. Thermosensitive hydrogels were prepared of poloxamer 407, alginate sodium, and cellulose derivatives and evaluated in terms of rheological and mucoadhesive behavior. The presence of chitosan altered the release profile of active compounds but did not affect their in vitro permeation behavior in PAMPA assay. The synergistic effects of S. baicalensis radix lyophilized extract and chitosan toward ferrous ion-chelating activity, inhibition of hyaluronidase, and pathogen growth were observed. The thermosensitive gelling system showed shear-thinning properties, gelation temperature between 25 and 27 °C, and favorable mucoadhesiveness in contact with porcine buccal mucosa, which was enhanced in the presence of binary mixture of S. baicalensis radix extract and chitosan. The release tests showed that baicalin and baicalein were liberated in a prolonged manner with a fast onset from hydrogel formulations.

The Influence of Tea Tree Oil on Antifungal Activity and Pharmaceutical Characteristics of Pluronic® F-127 Gel Formulations with Ketoconazole.

Fungal skin infections are currently a major clinical problem due to their increased occurrence and drug resistance. The treatment of fungal skin infections is based on monotherapy or polytherapy using the synergy of the therapeutic substances. Tea tree oil (TTO) may be a valuable addition to the traditional antifungal drugs due to its antifungal and anti-inflammatory activity. Ketoconazole (KTZ) is an imidazole antifungal agent commonly used as a treatment for dermatological fungal infections. The use of hydrogels and organogel-based formulations has been increasing for the past few years, due to the easy method of preparation and long-term stability of the product. Therefore, the purpose of this study was to design and characterize different types of Pluronic® F-127 gel formulations containing KTZ and TTO as local delivery systems that can be applied in cases of skin fungal infections. The influence of TTO addition on the textural, rheological, and bioadhesive properties of the designed formulations was examined. Moreover, the in vitro release of KTZ, its permeation through artificial skin, and antifungal activity by the agar diffusion method were performed. It was found that obtained gel formulations were non-Newtonian systems, showing a shear-thinning behaviour and thixotropic properties with adequate textural features such as hardness, compressibility, and adhesiveness. Furthermore, the designed preparations with TTO were characterized by beneficial bioadhesive properties. The presence of TTO improved the penetration and retention of KTZ through the artificial skin membrane and this effect was particularly visible in hydrogel formulation. The developed gels containing TTO can be considered as favourable formulations in terms of drug release and antifungal activity.

Cyclodextrin as Functional Carrier in Development of Mucoadhesive Tablets Containing Polygoni cuspidati Extract with Potential for Dental Applications.

Polygoni cuspidati root is a resveratrol-rich source with anti-inflammatory, angiogenic and neuroprotective effects. The raw material was standardized for the content of resveratrol, for which there is a special justification for administration within the oral mucosa. To improve the solubility of resveratrol and to assure its high content in plant material, an ultrasound-assisted extraction method was applied. The addition of cyclodextrin was found to increase the extraction efficiency of resveratrol (from 13 to 297 µg per 1 g of plant material in case of 50% ethanol extracts) and enhanced its antioxidant activity as compared to pure Polygoni cuspidati extract/resveratrol. Cyclodextrin plays the role of a functional extract regarding technological properties (increasing the extraction of resveratrol from the extract, improving mucoadhesive properties). Therefore, the aim of this study was to develop mucoadhesive tablets containing combinations of the Polygoni cuspidati extract with a cyclodextrin carrier for buccal delivery. The tests sequentially included extract preparation and characterization of its physical and biological properties and then formulation studies with a broad description of the prototype properties. The test results indicate that cyclodextrin increases the efficiency of resveratrol extraction from Polygoni cuspidati rhizome, which is a rich source of resveratrol, and its extract enclosed in a mucoadhesive tablet guarantees prolonged action at the site of administration.

Potential of mucoadhesive chitosan glutamate microparticles as microbicide carriers - antiherpes activity and penetration behavior across the human vaginal epithelium.

Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challenges associated with vaginal microbicide delivery. This study aimed at elucidating the penetration and mucoadhesive behavior of developed gCS multiunit carriers with zidovudine (ZVD) as a model antiretroviral agent in contact with excised human vaginal epithelium followed with an examination of in vitro antiherpes activity in immortal human keratinocytes HaCaT and human vaginal epithelial cells VK2-E6/E7. Both ZVD dispersion and placebo microparticles served as controls. Microparticles displayed feasible (comparable to commercial vaginal product) mucoadhesive and mucoretention characteristics to isolated human vaginal tissue. Ex vivo penetration studies revealed that gCS increased the accumulation of active agent in the vaginal epithelium but surprisingly did not facilitate its penetration across human tissue. Finally, the obtained antiviral results demonstrated the potential of gCS as an antiherpes adjunctive, whose mode of action was related to blocking viral attachment.

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.