Papers by Emilia Szymańska
International journal of molecular sciences, Mar 28, 2024
Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharm... more Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.
International journal of molecular sciences, Mar 28, 2024
Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharm... more Multifunctional delivery systems capable of modulating drug release and exerting adjunctive pharmacological activity have attracted particular attention. Chitosan (CS) and pomegranate seed oil (PO) appear to be attractive bioactive components framing the strategy of complex therapy and multifunctional drug carriers. This research is aimed at evaluating the potential of CS in combination with PO in studies on topical emulgels containing hydrocortisone as a model anti-inflammatory agent. Its particular goal was to distinguish alterations in anti-inflammatory action followed with drug dissolution or penetrative behavior between the designed formulations that differ in CS/PO weight ratio. All formulations favored hydrocortisone release with up to a two-fold increase in the drug dissolution rate within first 5 h as compared to conventional topical preparations. The clear effect of CS/PO on the emulgel biological performance was observed, and CS was found to be prerequisite for the modulation of hydrocortisone absorption and accumulation. In turn, a greater amount of PO played the predominant role in the inhibition of hyaluronidase activity and enhanced the anti-inflammatory effect of preparation E-3. Emulgels showed a negligible reduction in mouse fibroblasts' L929 cell viability, confirming their non-irritancy with skin cells. Overall, the designed formulation with a CS/PO ratio of 6:4 appeared to be the most promising topical carrier for the effective treatment of inflammatory skin diseases among the tested subjects.
International Journal of Biological Macromolecules
Pharmaceutics, 2021
Polygoni cuspidati root is a resveratrol-rich source with anti-inflammatory, angiogenic and neuro... more 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 ...
International Journal of Molecular Sciences, 2021
Fungal skin infections are currently a major clinical problem due to their increased occurrence a... more 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 de...
Drug Delivery, 2021
Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challen... more 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.
Pharmaceutics, 2021
Buccal films are recognized as easily applicable, microbiologically stable drug dosage forms with... more 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...
European Polymer Journal, 2020
Abstract Chitosan, a biocompatible positively charged polysaccharide from natural origin,is regar... more Abstract Chitosan, a biocompatible positively charged polysaccharide from natural origin,is regarded as a promising compound in medical and pharmaceutical technology. However, despitehigh application potential of chitosan, its susceptibility to the presence of ions, pH – dependent solubility, insufficient rheological properties or poor mechanical characteristics, can be a serious limitation in the technology of modified release drug carriers. To date, different strategies have been applied to overcome too rapid disintegration of chitosan carriers and to improve theirphysical properties. Among modifications of chitosan backbone, particular attention has been paid toward polyelectrolyte complexes spontaneously formed by mixing chitosan with oppositely charged polymers from both natural or synthetic origin under mild conditions. The aim of this review is to highlight the most recent advances and current applications of chitosan – based polyelectrolyte complexes as potential drug delivery systems and medical devices for local (skin and mucosal) application. Regarding the fact that pharmaceutical processing appears particularly important in proper polyelectrolyte complexes formation, this review covers the influence of selected technological factors on final polyelectrolyte complexes characteristics. The influence of a type of an applied polyanion on the polyelectrolyte complexes properties including swelling capacity, bio – and mucoadhesiveness or biological activity was also briefly described.
Materials, 2021
Etodolac (ETD), a nonsteroidal anti-inflammatory drug, exhibits antinflammatory, analgesic, and a... more Etodolac (ETD), a nonsteroidal anti-inflammatory drug, exhibits antinflammatory, analgesic, and antipyretic activity. The main type of ETD administration is oral route, which is associated with significant systemic side effects. Nanostructured lipid carriers (NLC), a modern lipid formulation, are non-toxic, biocompatible, can improve the solubility and stability of drugs. Nanostructured lipid carriers (NLC) containing etodolac were prepared by a melt-emulsification and ultrasonication technique. Full factorial design (FFD) was applied to optimize the composition of NLC and their properties such as zeta potential, polidyspersity index, and entrapment efficiency. Formulations consisting of Capryol 90, glicerol monostearate, and Tween 20 displayed particle size below 300 nm, encapsulated drug with efficiency of approximately 87% and prolonged drug release up to 24 h. Stable formulations displayed moderately negative surface charge suggesting their limited ability to interact with skin ...
Pharmaceutics, 2021
The health benefits of resveratrol have been proven to inhibit the development of numerous diseas... more The health benefits of resveratrol have been proven to inhibit the development of numerous diseases. A frequent limitation in its use is a low bioavailability stemming from a poor solubility and fast enterohepatic metabolism. Thus, the aim of the research was to investigate the possibility to formulate mucoadhesive cyclodextrin- and xanthan gum-based buccal tablets in order to increase the solubility of resveratrol and to eliminate bypass enterohepatic metabolism. Systems of resveratrol with α-cyclodextrin (α-CD), β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) prepared by the dry mixing method (ratio 1:1) were selected for the of tablets where xanthan gum was used as a mucoadhesive agent. They were identified on the basis of PXRD, FT-IR analysis. Tablets F1 (with α-CD), F2 (with β-CD) and F3 (with γ-CD) were characterized by the highest compactibility as well as by favorable mucoadhesive properties. Resveratrol release from these tablets wa...
Materials, 2020
Polyelectrolyte complexes based on the electrostatic interactions between the polymers mixed are ... more 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.
Journal of Clinical Medicine, 2020
Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as i... more Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as isoquinoline alkaloids (e.g., chelidonine, sanguinarine), flavonoids, saponins, carotenoids, and organic acids. Due to the presence of isoquinoline alkaloids, Chelidonii herba extracts are widely used as an antibacterial, antifungal, antiviral (including HSV-1 and HIV-1), and anti-inflammatory agent in the treatment of various diseases, while chitosan is a biocompatible and biodegradable carrier with valuable properties for mucoadhesive formulations preparation. Our work aimed to prepare mucoadhesive vaginal drug delivery systems composed of Chelidonii herba lyophilized extract and chitosan as an effective way to treat vaginitis. The pharmacological safety of usage of isoquinoline alkaloids, based on MTT test, were evaluated for the maximum doses 36.34 ± 0.29 µg/mL and 0.89 ± 1.16 µg/mL for chelidonine and sanguinarine, respectively. Dissolution rate profiles and permeability through arti...
Pharmaceutics, 2020
Microparticles containing water-soluble zidovudine were prepared by spray-drying using chitosan g... more 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 revea...
International Journal of Polymer Science, 2018
The physicochemical characteristics of beta-glycerophosphate-crosslinked chitosan hydrogels were ... more The physicochemical characteristics of beta-glycerophosphate-crosslinked chitosan hydrogels were investigated upon long-term storage at ambient, accelerated, and refrigerated conditions and compared to unmodified chitosan formulations. Additionally, the impact of chitosan modification on the ex vivo mucoadhesive performance in contact with porcine vaginal mucosa and on the drug release profile from hydrogels was evaluated. Viscosity and mechanical properties of formulations with unmodified chitosan decreased significantly upon storage regardless of tested conditions as a result of hydrolytic depolymerization. Introduction of ion crosslinker exerted stabilizing effect on physicochemical performance of chitosan hydrogels but only upon storage at refrigerated conditions. Beta-glycerophosphate-modified chitosan formulations preserved organoleptic, rheological behavior, and hydrogel structure up to 3-month storage at 4 ± 2°C. Viscosity variations upon storage influenced markedly mucoadhe...
Polymers, 2020
Periodontal diseases are some of the most widespread oral afflictions, and they are labeled as ch... more Periodontal diseases are some of the most widespread oral afflictions, and they are labeled as chronic infections caused by the accumulation of bacteria in dental plaque that produces localized inflammation of the periodontium. The use of local drug delivery systems to treat periodontal diseases has received greater attention, because the active substance is targeted directly to the affected area, which minimizes its systemic side effects. Therefore, the purpose of the investigation was to develop and characterize different types of gel formulations—bigel, hydrogel and oleogel—as local delivery systems containing metronidazole (MET), which can be applied to the oral mucosa. The influence of the formulation type on the mechanical, rheological and mucoadhesive properties were examined. Moreover, in vitro release of metronidazole, its ex vivo permeation through buccal porcine mucosa and antimicrobial activity measured by the plate diffusion method were estimated. It was found that the ...
Marine Drugs, 2016
Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray dryin... more Chitosan microparticulate delivery systems containing clotrimazole were prepared by a spray drying technique using glycerol 2-phosphate as an ion cross-linker. The impact of a cross-linking ratio on microparticle characteristics was evaluated. Drug-free and drug-loaded unmodified or ion cross-linked chitosan microparticles were examined for the in vitro cytotoxicity in VK2/E6E7 human vaginal epithelial cells. The presence of glycerol 2-phosphate influenced drug loading and encapsulation efficacy in chitosan microparticles. By increasing the cross-linking ratio, the microparticles with lower diameter, moisture content and smoother surface were observed. Mucoadhesive studies displayed that all formulations possessed mucoadhesive properties. The in vitro release profile of clotrimazole was found to alter considerably by changing the glycerol 2-phosphate/chitosan ratio. Results from cytotoxicity studies showed occurrence of apoptotic cells in the presence of chitosan and ion cross-linked chitosan microparticles, followed by a loss of membrane potential suggesting that cell death might go through the mitochondrial apoptotic pathway.
International journal of molecular sciences, Jan 28, 2018
Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for ef... more Mucoadhesive gelling systems with tannic acid modified silver nanoparticles were developed for effective treatment of herpes virus infections. To increase nanoparticle residence time after local application, semi solid formulations designed from generally regarded as safe (GRAS) excipients were investigated for their rheological and mechanical properties followed with ex vivo mucoadhesive behavior to the porcine vaginal mucosa. Particular effort was made to evaluate the activity of nanoparticle-based hydrogels toward herpes simplex virus (HSV) type 1 and 2 infection in vitro in immortal human keratinocyte cell line and in vivo using murine model of HSV-2 genital infection. The effect of infectivity was determined by real time quantitative polymerase chain reaction, plaque assay, inactivation, attachment, penetration and cell-to-cell assessments. All analyzed nanoparticle-based hydrogels exhibited pseudoplastic and thixotropic properties. Viscosity and mechanical measurements of hydr...
Pediatria i Medycyna Rodzinna, 2017
Preparaty donosowe z mometazonu furoinianem uważane są za wysoce skuteczne i bezpieczne w stosowa... more Preparaty donosowe z mometazonu furoinianem uważane są za wysoce skuteczne i bezpieczne w stosowaniu zarówno u dorosłych, jak i u dzieci. Dostępne aerozole do nosa charakteryzują się właściwościami tiksotropowymi i mukoadhezyjnymi, umożliwiającymi łatwą aplikację leku oraz wydłużającymi czas jego przebywania w jamie nosa. Zdolność do tiksotropii czy mukoadhezji nie jest wielkością stałą, lecz uwarunkowaną obecnością odpowiednich substancji pomocniczych w składzie preparatu. Celem pracy było porównanie właściwości reologicznych i mechanicznych wybranych preparatów z mometazonu furoinianem w postaci aerozolu do nosa. Preparaty te zostały ponadto poddane badaniom właściwości mukoadhezyjnych ex vivo-w tym celu wykorzystano świńską błonę śluzową nosa. W przeprowadzonych doświadczeniach wykazano różnice w lepkości i właściwościach tiksotropowych poszczególnych preparatów w zależności od temperatury pomiaru. Wszystkie analizowane preparaty w warunkach ex vivo charakteryzowały się zdolnością do mukoadhezji. Zaobserwowano zależność między lepkością i strukturą preparatów a ich właściwościami przylegania do świńskiej błony śluzowej nosa. Wykazano istotny wpływ procesu wstrząsania na twardość i spoistość preparatów. Słowa kluczowe: furoinian mometazonu, aerozol do nosa, mukoadhezja, cechy reologiczne Intranasal preparations with mometasone furoate are recognised to be highly efficient and safe in both adults and children. Commercially available nasal sprays are characterised by thixotropic and mucoadhesive properties-factors ensuring effortless drug dosing followed by prolonged retention time in the nasal cavity. Thixotropy and mucoadhesiveness is not a constant value and it is determined by the presence of proper excipients in the preparation's composition. The aim of the study was to compare rheological and mechanical properties of selected nasal spray formulations with mometasone furoate. In addition, these preparations were investigated for their ex vivo mucoadhesive behaviour to the porcine nasal mucosa. These experiments revealed differences in viscosity and thixotropic properties between nasal sprays depending on the measurement temperature. All analysed preparations possessed mucoadhesive properties in ex vivo conditions. Viscosity and mechanical measurements of the analysed preparations were found to be correlated with the mucoadhesive behaviour in contact with porcine nasal mucosa. An important role of the agitation process on the formulations' hardness and consistency was also demonstrated.
International Journal of Polymer Science, 2016
Over the last decades, alginates, natural multifunctional polymers, have increasingly drawn atten... more Over the last decades, alginates, natural multifunctional polymers, have increasingly drawn attention as attractive compounds in the biomedical and pharmaceutical fields due to their unique physicochemical properties and versatile biological activities. The focus of the paper is to describe biological and pharmacological activity of alginates and to discuss the present use and future possibilities of alginates as a tool in drug formulation. The recent technological advancements with using alginates, issues related to alginates suitability as matrix for three-dimensional tissue cultures, adjuvants of antibiotics, and antiviral agents in cell transplantation in diabetes or neurodegenerative diseases treatment, and an update on the antimicrobial and antiviral therapy of the alginate based drugs are also highlighted.
Molecules, 2015
The objective of this work was to design and characterize liquid and solid self-emulsifying drug ... more The objective of this work was to design and characterize liquid and solid self-emulsifying drug delivery systems (SEDDS) for poorly soluble atorvastatin. To optimize the composition of liquid atorvastatin-SEDDS, solubility tests, pseudoternary phase diagrams, emulsification studies and other in vitro examinations (thermodynamic stability, droplet size and zeta potential analysis) were performed. Due to the disadvantages of liquid SEDDS (few choices for dosage forms, low stability and portability during the manufacturing process), attempts were also made to obtain solid SEDDS. Solid SEDDS were successfully obtained using the spray drying technique from two optimized liquid formulations, CF3 and OF2. Despite liquid SEDDS formulation, CF3 was characterized by lower turbidity, higher percentage transmittance and better self-emulsifying properties, and based on the in vitro dissolution study it can be concluded that better solubilization properties were exhibited by solid formulation OF2. Overall, the studies demonstrated the possibility of formulating liquid and solid SEEDS as promising carriers of atorvastatin. SEDDS, with their unique solubilization properties, provide the opportunity to deliver lipophilic drugs to the gastrointestinal tract in a solubilized state, avoiding dissolution-a restricting factor in absorption rate of BCS Class 2 drugs, including atorvastatin.
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Papers by Emilia Szymańska