Katarzyna Winnicka

Background: Oxidative and nitrosative stress may contribute to the pathogenesis of oral lichen planus (OLP). This study compared the effects of photodynamic therapy (PDT) and topical corticosteroid therapy (CT) on selected salivary redox biomarkers. Materials and Methods: Thirty-nine patients with OLP were randomized to five weekly sessions of 5-aminolevulinic acid PDT (n = 20) or topical clobetasol applied for 14 days (n = 19). Salivary advanced oxidation protein products (AOPP), advanced glycation end products (AGE), 3-nitrotyrosine (NT), and peroxynitrite (PN) were measured before treatment, immediately after treatment, and after 6 and 12 months. Associations with lesion area and pain intensity were also assessed. Results: PDT significantly reduced AOPP concentrations, which remained below baseline throughout follow-up and were lower than after CT at all post-treatment assessments. AGE increased transiently after PDT but decreased thereafter and was lower than after CT at 12 months. NT was lower after PDT than after CT immediately after treatment. PN concentrations showed significant within-group changes over time in the CT group; however, baseline PN concentrations differed between the treatment groups, limiting direct interpretation of between-group differences. Biomarker concentrations showed no consistent associations with lesion area or pain intensity. Conclusions: PDT and CT were associated with different patterns of change in selected salivary redox biomarkers in OLP. PDT was particularly associated with a sustained reduction in AOPP concentrations, whereas the investigated biomarkers showed no consistent relationship with clinical disease severity.

Background/Objectives: Vaginal administration enables optimal drug concentrations at the site of administration, but its effectiveness is limited by factors such as the vagina’s self-cleansing mechanisms and fluctuations in physiological conditions. Due to the difficulties in treating and the frequent recurrences of vaginal candidiasis, new drug formulations are required to ensure more effective therapy and sustained release of antifungal agents. Mucoadhesive vaginal sponges are a promising drug formulation providing prolonged release of the active ingredient and its contact with the vaginal mucosa. The application of polymers and their modifications plays a key role in the development of drug forms with unique and desired technological parameters. Methods: Therefore, the focus of this research was the development of a three-stage sodium alginate cross-linking technique based on polyelectrolyte complexes with gelatin and ɛ-poly-L-lysine, and additional ionic cross-linking with zinc ions, to obtain mucoadhesive vaginal sponges with an antifungal agent—luliconazole. The prepared formulations were evaluated for their pharmaceutical, mechanical, and mucoadhesive properties. In addition, antifungal and anti-biofilm action against Candida strains and compatibility with the vaginal VK2 E6/E7 epithelial cell line of the prepared sponges were assessed. Results: It was noted that the triple cross-linking process increased the mechanical properties of the developed sponges, improved mucoadhesive properties to vaginal mucosa of drug-loaded formulations, and demonstrated a sustained LUL release profile. Moreover, prepared sponges possessed improved antifungal and anti-biofilm effects against C. albicans, C. krusei, and C. parapsilosis. The prepared triple cross-linked formulations were biocompatible with the human vaginal VK2 E6/E7 epithelial cell line, depending on the exposure time and applied concentration. Conclusions: Triple cross-linked alginate sponges containing luliconazole were successfully prepared based on polyelectrolyte complexes with gelatin and ɛ-poly-L-lysine and additional ionic cross-linking with zinc ions. The triple cross-linking process of alginate improved the mechanical, mucoadhesive, and antifungal properties of the developed formulations.

Dry skin and skin barrier dysfunction are common dermatological problems associated with increased transepidermal water loss (TEWL) and reduced stratum corneum hydration. Among moisturizing agents, trehalose—a naturally occurring disaccharide—has attracted considerable attention due to its moisturizing, protective, and stabilizing properties. The aim of this study was to develop dermatological emulsions with desirable physicochemical, rheological, mechanical, adhesive, and moisturizing properties for dry skin care. Six placebo emulsions, differing in emulsifier and oil compositions, were prepared and evaluated for stability, pH, viscosity, rheological behavior, texture, adhesion, and spreadability. Based on the results obtained, the formulation containing avocado oil and Olivem 1000 was selected as the optimal base for incorporating trehalose at concentrations of 1%, 2.5%, and 5%. The formulations were further evaluated in vivo using TEWL and corneometry measurements. All emulsions exhibited non-Newtonian shear-thinning and thixotropic properties. Regular application of the emulsions reduced TEWL by approximately 33%, while skin hydration increased up to 102%. However, discontinuation of the emulsion application resulted in decreased skin hydration and increased TEWL, suggesting the need for constant use.

Background/Objectives: Enteric drug forms are developed to delay drug release to avoid drug degradation in the acidic environment of the stomach or to prevent irritation of the stomach mucosa. The bioavailability of posaconazole (POS) after oral administration depends on stomach pH and food intake. Delayed-release tablets and unmodified oral suspension are the POS formulations currently available on the market. The oral suspension formulation is characterized by highly variable bioavailability, which may significantly affect therapy effectiveness. Methods: In this study, multi-unit drug forms with delayed and sustained POS release were designed. Polymeric microparticles consisting of sodium alginate (ALG), methacrylic acid–ethyl acrylate copolymer (EUD), or both, were prepared using the spray-drying technique. The formulations that met the pharmacopoeia enteric release standards in the in vitro dissolution test were subjected to further in vitro evaluation via swelling and mucoadhesion assays, an antifungal activity test, attenuated total reflectance–Fourier transform infrared spectroscopy (ATR-FTIR), and thermal analysis. Results: It was shown that EUD formulations at concentrations of 5% and 6% provided enteric release, whereas ALG at 1.5% concentration exhibited a sustained, although not delayed, POS release profile. The optimal blended formulations (EAP15–EAP18), comprising 4% EUD with 1.5–2.0% ALG and either 1% or 4% POS, met the pharmacopoeia criteria for enteric dosage forms. Furthermore, these blends demonstrated the most favorable sustained-release profiles in the buffer phase, ranging from 2 to 3 h. The microparticles exhibited beneficial swelling and mucoadhesive properties, which are essential for prolonging contact with the intestinal mucosa; combined with antifungal properties. Conclusions: Obtained carrier may provide a promising preliminary basis for developing a multi-unit, sustained-release enteric dosage form for POS and future in vivo investigations.

Disorders in the oral cavity caused by pathogenic fungi pose a significant clinical challenge, particularly in immunocompromised patients, as well as those undergoing oncological therapy or antibiotic treatment. A practical therapeutic approach involves the topical application of mucoadhesive drug dosage forms. However, only a limited number of such preparations are available on the pharmaceutical market. Mucoadhesive systems are especially advantageous, as they ensure prolonged retention and adequate concentrations of the active substances at the site of infection. Localized drug delivery enhances therapeutic efficacy compared to systemic administration, enabling lower drug doses, and consequently reducing the risk of side effects. Moreover, many fungal conditions require long-term treatment, which may be optimized by the use of mucoadhesive systems, improving patient compliance. Considering the issue of limited adhesion of conventional drug dosage forms and the moist environment in the oral cavity, providing optimal mucoadhesive properties is a key aspect. This article presents a comprehensive overview of the significance of treating oral candidiasis using mucoadhesive drug dosage forms, the mechanisms and advantages of mucoadhesion (including relevant polymers), and, most importantly, recent scientific reports on the development and quality assessment of mucoadhesive drug delivery systems for the management of oral fungal diseases.

In this randomized clinical trial, we compared the effects of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) and topical clobetasol on the salivary antioxidant profile in patients with oral lichen planus (OLP) and explored their relationships with clinical outcomes. Ninety adults with OLP were randomly allocated to ALA-PDT (five weekly sessions) or clobetasol (twice daily for 14 days). Unstimulated whole saliva was collected at baseline (T0), immediately after treatment (T1), and at 3 (T3) and 6 months (T6). The activities of catalase (CAT), superoxide dismutase (SOD), peroxidase (Px) and reduced glutathione (GSH) were determined, and nonparametric statistics were applied, including Friedman tests with Dunn’s post hoc comparisons and Spearman’s rank correlations. Both therapies induced an early decline in CAT, Px and GSH at T1, followed by partial recovery at later time points. SOD activity changed significantly over time in the clobetasol group, but not in the PDT arm. At T6, Px and GSH remained below baseline in both groups despite improvement from the immediate post-treatment nadir. No significant between-group differences were observed at individual time points, although GSH at T6 showed a non-significant trend favoring PDT. Exploratory analyses revealed modest, treatment-dependent associations between salivary antioxidant activity and lesion size, as well as between the former and pain intensity. Overall, ALA-PDT and topical clobetasol both modulated the salivary redox profile, primarily through short-term depletion of enzymatic and non-enzymatic antioxidants with incomplete recovery over 6 months, and no clear redox superiority of one modality over the other was demonstrated. These findings are hypothesis-generating and underscore the need for larger, longer-term studies with broader redox panels and more advanced between-group analyses.

Objective: Oral lichen planus (OLP) is a chronic immune-mediated condition of the oral mucosa, commonly associated with pain and burning sensations that impair quality of life. This study aimed to compare the efficacy of photodynamic therapy with 5-aminolevulinic acid (ALA-PDT) and topical glucocorticosteroids (CT) in the treatment of OLP, considering lesion location on keratinized and non-keratinized mucosa. Materials and Methods: A randomized clinical trial was conducted on 90 patients with histologically confirmed OLP. Participants were allocated to receive either ALA-PDT in addition to novel oromucosal emulgel containing 5% ALA (five weekly sessions) or clobetasol propionate applied twice daily for two weeks. Lesion area, clinical severity (Reticulation, Erythema, Ulceration—REU index), and subjective symptoms (Visual Analog Scale—VAS) were evaluated before treatment, immediately after, and six months after therapy. Results: ALA-PDT achieved significantly greater and more durable reductions in lesion area, REU scores, and VAS values compared to CT, particularly on non-keratinized mucosa (mean lesion reduction from 2.64 to 0.56 cm² at six months; p < 0.0001). CT therapy showed initial improvement but was followed by relapse at six months. Both treatments were well tolerated, with only mild transient adverse effects reported. Conclusions: ALA-PDT, especially when applied to non-keratinized oral mucosa, provides superior and longer-lasting therapeutic outcomes than topical CT. The application of novel ALA-loaded emulgel enhances treatment efficacy and tolerability, supporting PDT as a promising alternative for OLP management.

Background: Solid dispersions (SDs) of etodolac (ETD), a poorly water-soluble drug model, were developed to enhance its solubility and dissolution rate by employing various preparation methods and hydrophilic or amphiphilic polymers. Methods: Polyvinylpyrrolidone-poly(vinyl acetate) copolymers (PVP/VA), hydroxypropyl methylcellulose (HPMC) and poloxamer were used as carriers, while cryo-milling and lyophilization were utilized as routine methods to SDs preparation. Obtained SDs were characterized by drug content, solubility, dissolution rate and moisture content. The physical structure of SDs was estimated via scanning electron microscopy (SEM), whereas differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were employed to assess the potential drug-carrier interactions. Results: SD formulations demonstrated enhanced solubility of ETD in aqueous media, including water and buffers (pH 5.5 and 7.4). DSC analysis confirmed that PVP/VA and poloxamer ensured better ETD dissolution and protection against recrystallization. Furthermore, FTIR indicated the formation of hydrogen bonds between ETD and polymer, particularly in lyophilized dispersions. Conclusions: The optimized SD formulation for ETD contained PVP/VA and/or poloxamer as carriers and was obtained via lyophilization. This SD formulation exhibited the most favorable properties, enhanced the solubility and dissolution of ETD in aqueous media and effectively reduced its crystallinity.

Objective: This study aimed to assess the impact of photodynamic therapy (PDT) and topical glucocorticosteroids (GKS) on total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) in the saliva of patients with oral lichen planus (OLP). Methods: Ninety patients with histopathologically confirmed OLP were randomly assigned to either the PDT group (n = 50) or the GKS group (n = 40). Unstimulated saliva samples were collected before treatment and at 1, 3, and 6 months post-therapy. TOS, TAC, and OSI were determined using colorimetric assays. Results: Both PDT and GKS significantly reduced TOS over the entire observation period. TAC decreased persistently after GKS but remained stable after PDT except for an initial decline. OSI was significantly lower immediately after PDT but did not show sustained differences. Overall, PDT more effectively and durably restored redox balance compared to GKS. Conclusions: Photodynamic therapy demonstrates superior long-term efficacy in modulating oxidative stress markers in saliva, supporting its role as a promising alternative to topical corticosteroids in managing OLP. Clinically, these findings suggest that PDT may offer a non-invasive, recurrence-reducing, and steroid-sparing treatment alternative for OLP, potentially improving long-term patient outcomes and reducing side effects associated with prolonged corticosteroid use.

Background/Objectives: Despite the continuous development of medicine, the treatment of dermatological fungal infections is difficult due to their chronic nature, recurrence, and resistance of some pathogens to standard therapies. In order to improve the effectiveness of treatment, not only are new active substances with antifungal activity synthesized, but new, unconventional carriers are also developed for substances already used. Methods: Therefore, the focus of this research was to evaluate the possibility of using a combination of two cross-linking techniques for sodium alginate ionic cross-linking with Zn²⁺ ions and electrostatic interaction with ε-poly-L-lysine. The pharmaceutical properties, antifungal activity against Candida strains, and compatibility with human fibroblasts of the designed hydrogels were assessed. Results: It was shown that the double cross-linking process increased the viscosity of the developed hydrogels, improved bioadhesive properties to hairless mice skin, and provided an extended release profile of the active substance. In addition, obtained formulations were characterized by improved antifungal effect against C. albicans, C. krusei, and C. parapsilosis. Prepared hydrogels expressed biocompatibility with human fibroblasts. Conclusions: Dual-cross-linked alginate hydrogels are a promising dermatological formulation that might improve the efficacy of posaconazole in the treatment of antifungal infections.