Nanotechnology is a rapidly emerging field in pharmaceutical sciences that has shown significant potential to enhance the bioavailability of drugs, particularly those with poor aqueous solubility. Numerous nanoscale drug delivery systems, including nanocrystals, nanosuspensions, and lipid- and polymer-based nanocarriers, have been developed to overcome pharmacokinetic limitations. Through the optimization of physicochemical properties, significant improvements in drug delivery performance can be achieved. This could potentially enable advancements in the therapeutic use of various active pharmaceutical ingredients while minimizing undesirable and potentially toxic side effects. Despite their novel advantages, the development of nanoscale carriers poses many challenges, including safety concerns, high production costs, a lack of standardization, and scalability issues. Advanced formulation technologies, such as 3D printing, artificial intelligence (AI), and machine learning (ML) approaches, can help to address these challenges as they offer opportunities to achieve uniformity and more efficient production. This review provides an overview of the critical physicochemical properties of nanoparticles and potential nanotechnological approaches to enhance solubility and bioavailability, highlighting both their advantages and limitations, and summarizes prospects for further improvement.

Background/Objectives: The buccal mucosa offers a promising non-invasive route for systemic drug delivery, particularly for hydrophilic compounds like captopril (CAP), which exhibit low permeability and are subject to gastrointestinal instability and first-pass metabolism. This study aimed to develop and characterize captopril-loaded, chitosan-based mucoadhesive buccal films with different permeation enhancers and to evaluate their physicochemical properties, drug release, cytocompatibility, and in vitro transport across a TR146 buccal epithelial cell model. Methods: Films were prepared by the solvent-casting method using chitosan as the film-forming polymer. Different enhancers were investigated, including organic acid salts of chitosan (ascorbate, citrate, and lactate) and chemical permeation enhancers (sodium lauryl sulfate, polyethylene glycol 400, Span 20, and EDTA). Results: The resulting films exhibited acceptable thickness, moisture content, appropriate mechanical properties, and good mucoadhesive strength. In vitro dissolution studies demonstrated rapid CAP release, with >50% released within 15 min and near-complete release by 180 min across all formulations. Cytotoxicity assessment via a Neutral Red uptake assay in TR146 cells confirmed high cell viability (>81%) after 4 h of exposure, indicating good biocompatibility. In vitro permeation experiments revealed that films prepared with chitosan ascorbate and chitosan lactate enhanced CAP transport compared to other formulations, achieving the highest flux and apparent permeability coefficients. Conclusions: These findings demonstrate that chitosan ascorbate and lactate salts effectively improve the buccal permeability of captopril while maintaining good film properties and biocompatibility. This work highlights the potential of chitosan ascorbate- and lactate-based mucoadhesive films as an efficient platform for the buccal delivery of CAP.

Ocular drug delivery presents significant challenges due to the unique anatomical and physiological barriers of the human eye, with the rapid precorneal elimination, limiting the bioavailability of conventional eye drops. Thermosensitive in situ gels have emerged as a promising delivery system to overcome these limitations by undergoing a reversible sol-to-gel transition upon contact with ocular surface temperature, which facilitates ease of administration as a liquid and subsequent transformation into a gel, thereby enhancing precorneal residence time, prolonging the drug release, and improving therapeutic efficacy. This review provides a comprehensive overview of thermos-responsive polymer-based ocular delivery systems, with a specific focus on poloxamers, poly(N-isopropylacrylamide), and cellulose derivatives. Particular attention is given to the physicochemical mechanisms of thermogelation, such as poloxamer micellization and micelle packing, as well as the role of auxiliary polymers in enhancing mucoadhesion, mechanical strength, and gel retention. Additionally, the review synthesizes findings from multiple experimental studies to highlight the critical formulation parameters essential for developing effective in situ gels, including sol-gel transition temperature and time, clarity, rheological behavior, gelling capacity, isotonicity, and ocular biocompatibility. By selecting an optimized thermosensitive in situ gel formulation with suitable characteristics, it becomes possible to develop effective delivery systems targeting both the anterior and posterior segments of the eye.

Background: Cyclodextrin (CD) polymers have attracted increasing attention due to their favourable drug delivery properties and broad pharmaceutical applicability. While the bioavailability and biological behaviour of native cyclodextrins have been extensively investigated, considerably less information is available regarding modified cyclodextrin polymers. Therefore, the present study aimed to investigate the permeation and cellular uptake of an epichlorohydrin-crosslinked β-cyclodextrin polymer using multiple in vitro and ex vivo models. Methods: Fluorescently labelled β-cyclodextrin polymers were applied in all experiments. Membrane permeation studies were performed using an in-line diffusion cell system with membranes of different pore sizes. In vitro transport and cellular uptake were investigated on HaCaT, Caco-2, and TR146 cell monolayers, while ex vivo permeation studies were carried out using skin, buccal, and intestinal tissues. Results: The results demonstrated a strong size-dependent transport behaviour across synthetic membranes. Cell monolayer studies revealed cell-line-dependent differences in polymer intracellular distribution. Lysosomal accumulation was observed in HaCaT and Caco-2 cells, whereas no intracellular accumulation was detected in TR146 cells. These findings suggest differences in polymer permeation among the investigated cell models. Ex vivo studies demonstrated the tissue permeation of cyclodextrin polymers, with marked accumulation within skin layers, indicating predominant dermal retention. Furthermore, strong correlations were identified between the in vitro and ex vivo skin and intestinal models. Conclusions: Overall, the findings demonstrate that β-cyclodextrin polymers exhibit complex, barrier-dependent transport behaviour across different biological models. The observed differences in permeation and intracellular localization suggest that multiple transport processes may contribute to their biological interactions, which provide a foundation for future studies aimed at elucidating the molecular mechanisms governing polymer uptake and permeation.

Nowadays, the pandemic events have brought vaccines back into the focus of scientific research. The adjuvants are extremely important for the effectiveness of vaccines. Research and development based on the modernization of ingredients enables the development of more effective adjuvants with a better risk-benefit ratio. In our study, we aimed to develop squalene-containing nanoemulsion adjuvants using modern surfactants. The ultras method was used to develop a squalene-based adjuvant. The size and zeta potential of the created nanoemulsion adjuvant systems and their stabilities were investigated by DLS techniques. Both in vitro and in vivo harmlessness were demonstrated. The immunoglobulin production-promoting effect (IgG and IgE) was tested. Using the ultrasound size reduction process, the achieved size range was less than 200 nm. The size and zeta potential of the preparation remain stable for several months without significant changes. The developed adjuvant was not toxic in Galleria mellonella larvae and in the fibroblast cell line. The formulation achieved similar IgG and IgE production to Addavax, with IgG and IgE levels two orders of magnitude higher after 45 days compared to the OVA dosing alone. In summary, we have successfully developed a modern tenside-containing squalene adjuvant.

Background: Menopause is characterised by a decline in oestrogen levels, leading to physical and psychological symptoms that significantly affect quality of life. Current parenteral oestradiol ester therapies, while effective, are often associated with side effects due to their oil-based formulations, including injection-site reactions and immune responses. Methods: In this study, we developed a water-soluble, polyethylene glycol cross-linked β-cyclodextrin (PEG–β-CD) polymer-based system for parenteral oestradiol delivery and evaluated its biocompatibility, solubility enhancement, immune compatibility, and pharmacokinetics. Results: Cytotoxicity assays using NIH-3T3 fibroblasts and RAW 264.7 macrophages showed minimal toxicity up to 10% (w/w). Phase-solubility studies demonstrated a significant increase in oestradiol solubility with the PEG–β-CD polymer, surpassing that of β-cyclodextrin or PEG alone. Dynamic light scattering and FTIR analyses confirmed successful complex formation, with submicron particles averaging 271 nm and physical incorporation of oestradiol into the polymer matrix. Macrophage activation assays and RT-qPCR analyses indicated an absence of immunogenic responses or pro-inflammatory cytokine induction. In vivo toxicity testing in Galleria mellonella larvae confirmed safety, while pharmacokinetic studies in Wistar rats revealed rapid initial absorption followed by stable, low-level serum concentrations comparable to those of commercially used oestradiol esters. Conclusions: These findings indicate that the PEG–β-CD polymer–oestradiol complex provides a safe, water-based alternative to traditional oil-based injections, with the potential to reduce side effects and improve patient compliance in postmenopausal hormone therapy.

Implantable devices have undergone enormous development in the past several decades and more results are expected as there are still unanswered questions. In manufacturing, a relatively new technology called three-dimensional (3D) printing has become increasingly involved, from which hot-melt extrusion (HME) coupled with fused deposition modeling (FDM) is one of the most researched methods in producing implantable drug delivery systems (IDDS). The HME process is used to produce polymer filaments that are the carriers of the applied drugs, while FDM creates the implant itself from the filaments, based on the computer-aided designs. The availability of several polymers like polycaprolactone, polylactic acid, or thermoplastic polyurethane, etc., allows the incorporation of many active pharmaceutical ingredients while digital designs offer numerous variabilities in designs, formulations, and applications of 3D-printed IDDS. This allows more specific and detailed modifications in the end product which can forecast the possibility of personalized treatments and therapies. In this review, our research group gathered together different HME-FDM-printed IDDS to provide examples about the diverse applicability of 3D printing. These products, just like any other device and medicine in the medical field, must be characterized and evaluated properly. The methods and technology that are needed already exist and can be repeatedly used in the characterization of IDDSs; we also discuss these methods based on the available publications. In conclusion, every condition is given to make research and manufacture personalized 3D-printed IDDSs possible, however more research work and proof of safe usage are crucial to make these devices applicable in everyday medical treatments.

Tapinarof is a novel aryl hydrocarbon receptor (AhR) agonist that has recently been approved for the treatment of psoriasis. Although its clinical efficacy has been proven, in psoriasis, hyperkeratotic plaques and damaged barrier hinder drug penetration from conventional creams and ointments, resulting in poor bioavailability in the deeper layers of the skin. Innovative drug delivery systems can improve targeted action and reduce potential side effects. The primary goal of this study was to evaluate whether tapinarof-loaded nanogels enhance the anti-inflammatory, anti-proliferative, and anti-migratory effects of tapinarof at the cellular level using an in vitro HaCaT-THP-1 co-culture model. Initially, experiments were performed using real-time cell analysis (RTCA), and a concentration of 10 µM was found to be the most effective, showing significant cell proliferation inhibition compared to imiquimod and free tapinarof. To demonstrate cell proliferation and migration during inflammatory conditions, a wound healing assay was performed, which showed inhibited cell migration. Subsequently, the levels of inflammatory cytokines (TNF-α, IFN-γ, IL-17A, IL-23) were analyzed by ELISA, which demonstrated that tapinarof incorporated into nanogels reduced cytokine production more effectively than the drug alone. Quantitative PCR (qPCR) analysis confirmed Imiquimod (IMQ)-induced upregulation of Tnf-α and Ifn-γ, whereas Il-17a and Il-23 did not show measurable transcriptional changes under the experimental conditions. Finally, inhibition of p65 subunit nuclear translocation were observed during NF-κB pathway activation in THP-1 cells by immunofluorescence staining. Overall, our results indicate that nanogel-based delivery systems exhibit enhanced biological effects of tapinarof compared to the free drug in an in vitro psoriasis-like co-culture model, highlighting their potential as therapeutic tools for the treatment of various inflammatory skin diseases.

Background: Artemisia annua L. is a medicinal plant with documented antimicrobial, antioxidant, and anti-inflammatory properties. Although widely studied for internal therapeutic applications, its topical use-especially in hydrogel-based systems-has not been thoroughly investigated. The aim of this study was to develop sodium alginate hydrogels containing Artemisia annua extract, supplemented with hyaluronic acid and dexpanthenol, and to evaluate their physicochemical characteristics as well as their biological activities in vitro and in vivo. Methods: Select bioactive constituents of the Artemisia annua extract were quantified using liquid chromatography coupled with electrospray ionization mass spectrometry (LC-ESI-MS). Hydrogels were prepared by cross-linking sodium alginate with a calcium carbonate-glucono-delta-lactone system and were formulated with or without hyaluronic acid and dexpanthenol. Physicochemical evaluations included measurements of moisture content, water-retention capacity, gelation time, and pH. The hydrogel microstructure was examined by scanning electron microscopy (SEM). Antioxidant activity was assessed using three methods: the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, the ferric reducing antioxidant power (FRAP) assay, and the cupric reducing antioxidant capacity (CUPRAC) assay. Biocompatibility and regenerative effects were analyzed using cell viability assays and an in vitro scratch wound model on human keratinocyte cells. In vivo wound-healing efficacy was examined in rats with full-thickness skin excisions. Results: The extract contained high levels of methylated flavonoids and sesquiterpenes characteristic of Artemisia annua. Hydrogels supplemented with hyaluronic acid and dexpanthenol exhibited improved hydration stability and higher porosity. All formulations demonstrated measurable antioxidant activity, and those containing hyaluronic acid showed the strongest effects. The preparations were biocompatible and enhanced keratinocyte migration in vitro, with the combined hyaluronic acid-dexpanthenol formulation promoting the fastest wound closure. In vivo, Artemisia annua hydrogels accelerated wound healing by two to three days compared with untreated wounds. Conclusions: These results confirm the promise of Artemisia annua hydrogels for topical wound care and highlight the beneficial contributions of hyaluronic acid and dexpanthenol to their structural and therapeutic performance.

Background: Early and adequate empiric antibiotic therapy is essential in the treatment of pneumonia and sepsis and may influence the clinical outcome. Aims and Objectives: This retrospective before-after study aimed to appraise the impact of a local Antibiotic Stewardship Program (ASP-written guidelines and antibiotic restriction) on antibiotic (AB) use and clinical outcomes in patients requiring intensive care due to pneumonia and sepsis. Methods: This study was conducted as a single-center, retrospective observational study in the intensive care unit (ICU) of a pulmonology department of a tertiary care center. Data were collected for the pre-intervention period between January 2018 and May 2022 and for the ASP period between June 2022 and March 2024. In addition to descriptive statistics and univariable methods, interrupted time series (ITS) analysis was used to assess AB use and length of stay in the ICU before and after ASP implementation, using a segmented linear regression with a fixed breakpoint and continuous (hinge) specification. Results: The patients admitted to the ICU with pneumonia and sepsis were mainly men (58/101, 57.4% and 84/128, 65.6%), the need for intensive care increased with age, and most of the patients belonged to 65+ age group in both study phases (69/101, 68.3% and 75/128, 58.6%). The majority of the patients had four or more comorbidities (58/101, 57.4% and 52/128, 40.6%). In-hospital mortality was relatively high (42.6% and 41.4%), with most of the patients losing their lives in the ICU (33/43, 76.7% and 37/53, 69.8%). Significant increase in guideline-adherent agent selection (34.5%) and use of combination therapy (35.0%) was observed, while the use of fluoroquinolones decreased significantly (-31.1%). In the after period, a significant decrease in the number of patients using restricted ABs (-53.3%) was observed. In one-third of these cases (10/34, 29.4% and 16/40, 40%), two to four multidrug-resistant pathogens (MDRs) were detected simultaneously, resulting in a significant increase in direct costs (10.5%) in the ICU. The inappropriate use of AB therapy was relatively low in the presence of MDRs in both phases (2/34, 5.9% and 6/40, 15%). In the ASP period, guideline adherence was associated with slightly better clinical outcomes (30-day mortality: -0.8%; length of stay: -22.6%) in pneumonia and sepsis. The ITS analyses after the ASP implementation showed a weak downward trend and before it a slight increasing trend. Conclusions: ASP implementation in the ICU resulted in a significant improvement in the appropriate use of ABs, and guideline adherence led to slightly better clinical outcomes. Our results suggest that ASP may offer improved antimicrobial resistance with a sustained long-term effect.

Background/Objectives: Intracellular delivery of RNA molecules is challenging. To solve this problem, many carrier systems are available, which are based on liposomes or polymers. Cyclodextrins are widely used excipients to increase the solubility of small molecules, but their polymer derivatives are able to deliver macromolecules. In the present study, we aimed to investigate and compare the siRNA and mRNA carrying capacity of a cationic quaternary ammonium β-cyclodextrin polymer (QABCDPS) and polyethylenimine (PEI). Methods: Cytotoxicity of the polymers was tested by the MTT method. Polyplexes were formulated with different nitrogen/phosphate ratios (NP), and their physicochemical properties were examined using dynamic light scattering and zeta potential measurements. Cellular internalization and intracellular effects of the polyplexes were investigated by confocal microscopy and flow cytometry. Results: QABCDPS exhibited lower toxicity compared to PEI, effectively binding both siRNA and mRNA and delivering them into vesicles in the cytoplasm, but showing different internalization patterns. Polyplexes formed with PEI showed stronger biological effect than those with QABCDPS, which can be attributed to the strength of interactions facilitated by the polymers. Conclusions: In summary, QABCDPS is a low-toxicity carrier that shows some promise for mRNA delivery but is ineffective for siRNA silencing under the tested conditions and requires further structural optimization.

Background: Buccal films have attracted continued interest due to their several advantages. However, developing effective buccal films for hydrophilic drugs remains challenging due to limited buccal permeability. Captopril, a water-soluble ACEI, represents a suitable model for evaluating buccal films. Chitosan–ascorbate has previously been studied in solution for its cytotoxicity and permeation-enhancing properties. However, its performance as a buccal-film dosage form requires further investigation. The present study extends earlier formulation work by evaluating the in vitro cytotoxicity, permeability, and stability of captopril-loaded chitosan–ascorbate buccal films. Methods: Blank and captopril-loaded films were assessed. Cytotoxicity and permeability were evaluated using TR146 cells and compared with chitosan–acetate films as a reference. Accelerated stability test (40 °C/75% RH, three months) was performed to monitor moisture content, mechanical properties, and drug content. FT-IR spectroscopy was used to investigate potential chemical interactions. Results: All films maintained cell viability above 80%. Chitosan–ascorbate films significantly increased captopril permeation compared with chitosan–acetate films, achieving up to a 12–16-fold increase in cumulative drug permeation. The stability test did not reveal any new chemical reactions or interactions based on FT-IR analysis, indicating that the polymer system remained structurally stable; however, it showed continuous moisture uptake, slight deterioration of mechanical properties and a decrease in drug content. Conclusions: This study provides an in vitro, dosage-form–level evaluation of captopril-loaded chitosan–ascorbate buccal films, demonstrating acceptable cytocompatibility and moderate enhancement of permeability. However, significant moisture sensitivity under accelerated conditions can represent limitations, highlighting the importance of protective packaging or further formulation optimization to overcome this.

The oral mucosa is a versatile surface for drug administration, supporting both local and systemic therapies. Many active substances are effectively absorbed in the oral cavity, offering an alternative to enteral administration by bypassing the harsh gastrointestinal environment and hepatic first-pass metabolism. This has made oral mucosal drug delivery a growing area of research. Enhancing the bioavailability of active ingredients is a key focus in pharmaceutical technology, especially given the challenges of developing new drugs. Numerous strategies to improve bioavailability are compatible with oral mucosal delivery, with the unique anatomy of the oral cavity enabling specialized applications. A variety of dosage forms tailored for oral mucosal delivery meet therapeutic needs while addressing biopharmaceutical and patient compliance challenges. Proper formulation can achieve controlled release, improved bioavailability, and patient convenience. This review highlights the potential of oral mucosal drug delivery, focusing on bioavailability enhancement methods and the types and production technologies of dosage forms optimized for use in the oral cavity.

Background/Objectives: Sepsis is one of the most common causes of death worldwide, and its diagnosis remains a challenge for clinicians. The main purpose of this study was to appraise the diagnosis and antibiotic prescription pattern for sepsis admitted to the Emergency Department (ED), comparing Sepsis-2 to Sepsis-3 criteria. Methods: The study was conducted in an ED of a tertiary care medical center in Hungary. We included all adult patients who were diagnosed with sepsis in 2023. Data collection was made manually from UD MED System. Diagnosis was assessed based on Sepsis-2 and Sepsis-3 criteria, then compared. Further analyses were made only in cases with confirmed sepsis diagnosis. Antibiotic guideline adherence was determined according to the local guideline in force. Fisher’s exact test, t-test, and ANOVA were applied to compare categorical and continuous variables between groups. The Kaplan–Meier test was applied for probability of survival. Significant p-values were defined as below 0.05. Results: The substantial majority of patients recorded with sepsis in the ED met both the Sepsis-2 and Sepsis-3 criteria (80%), while the rate of misdiagnosis was similar (Sepsis-2: 16/91, 17.6% and Sepsis-3: 14/91, 15.4%). The most important identified risk factors in sepsis were old age (60+ years) and comorbidities (CCI ≥ 4). Elevated LDH (median 325 mg/dL) and decreased albumin levels (median 26 g/L) can be used as early indicators of sepsis. Although the time to first antibiotic administration was not associated with significantly better clinical outcomes, the guideline-adherent agent selection (Sepsis-2: 18/43, 41.9% and Sepsis-3: 19/46: 41.3%) led to a significantly longer survival (median 37 vs. 4 days). Conclusions: No significant differences were found in diagnostic accuracy or prediction of mortality between Sepsis-2 and Sepsis-3. Guideline-adherent antibiotics may lead to significantly higher survival rate in sepsis.

Background: Centaurium erythraea Rafn. (C. erythraea) is a medicinal plant traditionally used in European folk medicine for the treatment of wounds, skin inflammations, and other dermatological conditions, in addition to its well-documented systemic antioxidant and anti-inflammatory effects. However, its topical applications remain insufficiently investigated, particularly using plant material collected from Romania. The purpose of this study was to prepare different ointment formulations containing C. erythraea Rafn. extract obtained from the aerial parts of the plant, using various excipients, and to evaluate their in vitro and in vivo efficacy. Methods: The phytochemical profile of C. erythraea extract was characterized using liquid chromatography–tandem mass spectrometry (LC–MS/MS). The lyophilized extract was pre-dissolved in different solubilizing agents—Transcutol® P (diethylene glycol monoethyl ether), Capryol® 90 (propylene glycol monocaprylate), or a combination of both—and then incorporated into five ointment formulations. Texture analysis and an in vitro membrane diffusion study were performed. The antioxidant capacity of the formulations was assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ferric reducing antioxidant power (FRAP), and total phenolic content (TPC) assays. Anti-inflammatory activity was evaluated in vitro using tumor necrosis factor-alpha (TNF-α)-induced interleukin-1 beta (IL-1β) production in human keratinocyte (HaCaT) cells, and in vivo using a carrageenan-induced rat paw edema model. Results: LC–MS/MS identified 18 polyphenolic compounds, with hyperoside (3.78 ± 0.05 µg/mL), protocatechuic acid (1.13 ± 0.06 µg/mL), chlorogenic acid (1.07 ± 0.06 µg/mL), and quercetin (0.53 ± 0.03 µg/mL) as the principal constituents. The formulation containing both Transcutol® P and Capryol® 90 exhibited the most pronounced antioxidant activity (65% DPPH inhibition; 69.71 ± 0.83 mg gallic acid equivalent/mL) and significantly reduced IL-1β levels by 45.7% compared to the inflamed control. In vivo, this formulation showed comparable anti-edematous effects to a methylprednisolone ointment. Furthermore, it demonstrated the highest skin permeation efficiency, with a quercetin diffusion coefficient of 35.12 × 10−5 cm2/min. Conclusions: These findings highlight the therapeutic potential of C. erythraea extract from aerial parts in topical formulations and underscore the enhancing role of Transcutol® P and Capryol® 90 in improving both the pharmacodynamic and pharmacokinetic properties of bioactive compounds.

INTRODUCTION:Epilepsy is one of the most common neurological disorders and requires long-term treatment with anti-seizure medication (ASM) which may cause adverse drug reactions (ADRs). Our aims were to investigate potential sex differences in reporting suspected ADR (sADRs) of ASMs through studying their seriousness, outcomes and Sudden Unexpected Death in Epilepsy (SUDEP). METHODS:Using EudraVigilance database, reported sADRs with different ASMs over a ten year period were extracted. List of ASMs was compiled according to Anatomical Therapeutic Chemical Classification System. Reporting Odds Ratio (ROR), 95 % confidence interval (95 % CI), p-value were calculated. RESULTS:In general, more sADRs were reported from females (603,936, 57.46 %). Males showed positive association with the following seriousness criteria: 'life threatening' (ROR=1.02, 95 %CI: 1.01-1.04; p < 0.001), 'caused/prolonged hospitalisation' (ROR=1.06, 95 %CI: 1.05-1.07; p < 0.001), 'results in death' (ROR=1.44, 95 %CI: 1.43-1.46; p < 0.001), and 'congenital anomaly' (ROR=2.43, 95 %CI: 2.41-2.45; p < 0.001). Only with 'not recovered / not resolved' outcome criteria showed negative association in males (ROR=0.72, 95 %CI: 0.70-0.73; p < 0.001), the other outcome criteria demonstrated positive association in the followings: 'fatal' (ROR=1.43, 95 %CI: 1.41-1.45; p < 0.001), 'recovered / resolved' (ROR=1.08, 95 %CI: 1.07-1.09; p < 0.001), 'recovered / resolved with sequelae' (ROR=1.06, 95 %CI: 1.01-1.12; p < 0.001), and 'recovering / resolving' (ROR=1.14, 95 %CI: 1.12-1.15; p < 0.001). CONCLUSION:Differences were observed between males and females, particularly in terms of seriousness criteria, worse outcomes but prone to recover, and associations with SUDEP to the detriment of males. When choosing an ASM for a patient or especially if the patient has previously experienced an adverse drug reaction. these aspects can also be taken into account and may be important.

Background/Objectives: The present study focused on the formulation and evaluation of novel topical systems containing Salvia officinalis (sage), emphasizing their antioxidant and anti-inflammatory properties. Sage, rich in carnosol, offers considerable therapeutic potential, yet its low water solubility limits its effectiveness in traditional formulations. The aim of our experimental work was to improve the solubility and thus bioavailability of the active ingredient by developing self-nano/microemulsifying drug delivery systems (SN/MEDDSs) with the help of Labrasol and Labrafil M as the nonionic surfactants, Transcutol HP as the co-surfactant, and isopropyl myristate as the oily phase. Methods: The formulations were characterized for droplet size, zeta potential, polydispersity index (PDI), encapsulation efficacy, and stability. The composition exhibiting the most favorable characteristics, with particle sizes falling within the nanoscale range, was incorporated into a cream and a gel, which were compared for their textural properties, carnosol penetration, biocompatibility and efficacy. Results: Release studies conducted using Franz diffusion cells demonstrated that the SNEDDS-based cream achieved up to 80% carnosol release, outperforming gels. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) test and enzyme-linked immunosorbent assays (ELISA) showed strong efficacy, with an in vivo carrageenan-induced rat paw edema model revealing that the SNEDDS-based cream significantly reduced inflammation. Conclusions: These findings highlight the potential of SNEDDS-enhanced topical formulations in improving therapeutic outcomes. Further research is warranted to confirm their long-term safety and efficacy.

Background/Objectives: Increasing the bioavailability of poorly absorbed drugs is a continuous challenge in modern pharmaceutical technology. This is due to the problematic nature of BCS class IV active pharmaceutical ingredients: these drugs possess poor solubility and membrane permeability. Moreover, many undergo immediate efflux and/or rapid systemic metabolism after absorption. This project aimed to improve the bioavailability of BCS class IV drugs by formulating gastroretentive self-emulsifying systems using curcumin as a model drug. Methods: The base of the systems was created by melting emulsifying agents, dissolution retardants, and PEGs together. Curcumin was added after the mixture was cooled slightly. Aqueous dispersions of several compositions were characterized by dynamic light scattering. After screening these results, the viscosities of the selected formulations were evaluated. Dissolution retardants were selected and added to the most superior samples, and their dissolution profiles were compared. Gastroretention of the final formulation was achieved by dispersing air in the molten system through melt foaming; internal structure was assessed by microCT, and physicochemical properties by PXRD and DSC. Cytotoxicity was measured in Caco-2 cells using MTT and Neutral Red assays, and transcellular transport was also studied. Results: Based on these results, a homogeneous gastric floating system was developed. We observed an advantageous cytotoxic profile and increased bioavailability. Conclusions: Overall, we were able to create a self-emulsifying gastroretentive formulation displaying extended release and gastric retention with a low amount of cost-efficient excipients.