The choice of dermal dosage form is critical for therapeutic success, as it directly influences drug absorption, bioavailability, and overall efficacy. The skin possesses distinct physiological and anatomical characteristics that determine the performance of topical formulations. In addition to efficacy, the selected dosage form affects patient comfort, treatment adherence, and overall therapeutic outcomes. Therefore, optimizing dermal formulations is essential. This study aimed to compare different diclofenac sodium-containing dermal dosage forms in terms of drug release, bioavailability, cytotoxicity, and anti-inflammatory activity. Three formulations were evaluated: cream, foam and gel. Texture analysis was performed to predict bioavailability. Drug release and membrane penetration were assessed using a Franz diffusion cell combined with UV–VIS spectrophotometry. Biocompatibility was determined by MTT assay on HaCaT human keratinocyte cells. The in vitro anti-inflammatory effect was evaluated by measuring TNF-α and IL-1β levels using ELISA. Franz diffusion studies demonstrated that the foam formulation exhibited the most favorable penetration profile, followed by the cream and gel. MTT results confirmed acceptable biocompatibility for all formulations; however, cream and gel showed a greater reduction in cell viability, likely due to excipients. The foam achieved the greatest reduction in inflammatory markers, while no significant difference was observed between cream and gel. Based on the results, it can be concluded that the foam formulation containing diclofenac sodium is the most advantageous in terms of drug release, bioavailability, toxicity, and anti-inflammatory effect.
Despite the serious progress in the antitumor therapy, cancer did not cease to be one of the leading causes of death in the developed world. Hence still there is high interest for new anticancer agents. In 2025, the EMA approved 104 new medicines, 37 of them containing new active substances. 18 new anticancer medicines were approved (14 new active substances). In this review, we aim to shortly summarize the mechanism of action and use of the new drugs approved by the EMA in the year 2025.
Background: Accurate renal function assessment is essential for appropriate antibiotic dosing in critically ill patients. However, different estimation equations may yield discrepant results, potentially leading to dosing errors and suboptimal clinical outcomes. Objectives: To compare antibiotic dosing appropriateness based on renal function estimated using Cockcroft–Gault (CG), MDRD, and CKD-EPI equations, and to evaluate associated clinical outcomes in ICU patients with pneumonia-associated sepsis. Methods: In this single-center retrospective observational study, 229 adult ICU patients were included. Renal function was estimated using CG, MDRD, and CKD-EPI equations. Antibiotic dosing was classified as appropriate or inappropriate according to SPC and local guidelines. Clinical outcomes, including 30-day mortality/survival, and length of stay (LOS) were analyzed. Results: Based on CKD-EPI and MDRD, 57.2% and 55.5% of patients received appropriate dosing, respectively. However, 7.4% of patients considered appropriately dosed by these equations were reclassified as inappropriately dosed using CG. While mean renal function values were similar across equations (~67 mL/min), median values differed by approximately 20 mL/min (CG: 74 mL/min vs. CKD-EPI/MDRD: 52 and 50 mL/min), leading to clinically relevant reclassification. Inappropriate dosing was associated with older age and higher comorbidity burden. Piperacillin/tazobactam was most frequently underdosed, whereas clarithromycin, cefepime, and amikacin were commonly overdosed. Patients with inappropriate dosing had longer hospital LOS (median 14 vs. 11 days) and ICU-LOS (9 vs. 6 days), and showed worse survival, although 30-day mortality differences were not significant. Conclusions: The choice of renal function equation significantly impacts antibiotic dosing decisions. CG-based assessment may better identify dosing inaccuracies, and inappropriate dosing is associated with worse clinical outcomes. Optimized, individualized dosing strategies are warranted in critically ill patients.
Cyclodextrin-based micro- and nanocarriers are increasingly being explored as versatile tools for improving the stability and delivery of probiotic microorganisms, addressing persistent challenges such as acid and bile sensitivity, oxidative stress, and processing-related losses. A wide range of micro- and nano-encapsulation strategies, including spray drying, extrusion, coacervation, freeze-drying, and electrospinning, have been developed to enhance probiotic viability and gastrointestinal performance. Within this technological landscape, cyclodextrins offer distinctive advantages due to their ability to form multifunctional carrier matrices and stabilize sensitive bioactive components through both inclusion and non-inclusion interactions. Beyond their role as formulation excipients, emerging evidence indicates that certain cyclodextrins may also exhibit prebiotic-like properties, selectively modulating gut microbiota composition and metabolic activity. This combination of carrier functionality and potential biological activity suggests a conceptual framework for synbiotic design in which cyclodextrins could both protect probiotics and influence the intestinal environment following release. Advances in cyclodextrin-based hydrogels, nanosponges, and hybrid polymer systems further illustrate opportunities for colon-targeted delivery, microbiota-responsive degradation, and controlled release; however, most probiotic-specific applications remain at an exploratory stage. Key challenges related to large-scale manufacturing, microbial viability, safety assessment, and regulatory harmonization remain unresolved. Rather than presenting a finalized technology, this review integrates evidence from food science, pharmaceutical research, and microbiome studies to highlight cyclodextrin-enabled probiotic formulation as an emerging research domain. By delineating current opportunities and limitations, the work aims to stimulate interdisciplinary investigation into the potential role of cyclodextrins in future probiotic and synbiotic systems
Poor aqueous solubility remains one of the major challenges in the development of orally administered drugs, particularly for lipophilic molecules such as ABCG2 transporter inhibitors. These compounds possess high molecular weight, significant lipophilicity, and limited water solubility, which restrict their bioavailability and therapeutic application. This study aimed to enhance the solubility of a model ABCG2 inhibitor using different solubilization techniques, including co-grinding with hydroxypropyl-β-cyclodextrin (HP-β-CD) or polyvinylpyrrolidone (PVP) and micellar solubilization using nonionic surfactants. Each formulation was optimized and characterized for drug loading, equilibrium solubility and dissolution behavior under simulated gastrointestinal conditions. The micellar formulation exhibited the highest solubilization efficiency, The HP-β-CD complex and PVP co-grinding dispersions also resulted in notable enhancement compared to the pure drug. These findings highlight the potential of simple formulation strategies to overcome solubility limitations of ABCG2 inhibitors and improve their oral bioavailability.
Male hypogonadism, or Testosterone Deficiency (TD), involves decreased testicular function, leading to low androgen levels and impaired sperm production. This condition can negatively impact quality of life and increase cardiovascular risks. The adult hypogonadism frequently occurs over 40 in men, and it is characterized by persistent symptoms alongside low testosterone levels, typically below 300 ng/dL. Supplementation with testosterone as a replacement therapy (TRT) is hormonal enhancement found to be effective, however the delivery methods vary, each with specific advantages and drawbacks. The TRT has potentially life-changing effects, patients feel improved quality of life in several aspects: more energy and muscular strength, increased libido, improved mood, etc. as the most ferquent patients reported outcome. Oral TRT, particularly testosterone undecanoate (TU), offers notable convenience. TU is absorbed via the lymphatic system, bypassing first-pass hepatic metabolism, making it a promising agent for TRT. Its absorption, however, is influenced by dietary factors, such as lipid intake, thus the high-fat consumption promoting lymphatic absorption. Pharmaceutical technology to address this dependency, newly developed TU formulations incorporate special self-emulsifying systems that enhance lymphatic absorption regardless of food fat content. This lymphatic absorption allows for stable testosterone levels, positioning TU as a viable also for an oral treatment option.
This study compares two gel bases in which either natural or synthetic active substances are incorporated: Philadelphus coronarius flower extract and BGP-15. The preparations were evaluated for texture analysis, in vitro drug release and pH characteristics. Gels were formulated using Carbopol 940 or hydroxypropyl methylcellulose (HPMC) as gelling agents. Texture analysis revealed comparable mechanical properties with slight increases in firmness upon incorporation of active substances. In vitro release studies demonstrated rapid early release for both gel bases, with Philadelphus coronarius reaching approximately 27% release at 180 minutes and BGP-15 achieving ~26% release. The findings support the dermal applicability of both agents and highlight their potential roles in natural and synthetic therapeutic skin preparations.
Therapeutic oligonucleotides are employed in the treatment of a variety of diseases, primarily functioning through mechanisms associated with gene silencing technologies. In contrast, aptamers exhibit mechanisms of action that are more akin to those of protein-based monoclonal antibodies. However, owing to their oligonucleotide structure, aptamers possess several advantages over antibodies. Despite these benefits, the adoption of aptamers in clinical medicine has not reached the levels observed with monoclonal antibodies or gene-silencing oligonucleotides. Almost two decades after the approval of pegaptanib, the first approved aptameric therapeutic for the treatment of neovascular AMD (age-related macular degeneration), a second aptamer has recently received approval to treat geographic atrophy, an advanced form of AMD. In this review, we aim to provide an overview of the pharmacology and chemistry of avacincaptad pegol, the second approved aptameric drug.
3D printing or additive manufacturing are conquering many industrial fields, just as the pharmaceutical industry. There are several types of additive manufacturing processes, however one technology, the fused deposition modeling is outstanding in the pharmaceutical field. Fused deposition modelling uses filaments for printing. These filaments are made out of polymers that has diverse properties, suitable for containing active pharmaceutical ingredients for various usages. These filaments can be produced by hot-melt extrusion process, that the pharmaceutical field already uses for several formulations. In order to get a useable filament, we need more machines than just the extruder. Through the process, the feeder, the conveyor and the winder machines are necessary to get the desired homogeneity, filament diameter, and a ready to use filament roll to easily couple hot melt extrusion with fused deposition modeling. Polymers for pharmaceutical usage are already exists, including polyethylene glycols, polylactic acids, hydroxypropyl cellulose and many more. Finding polymers that has the appropriate rheological properties, heat- and chemical stability to apply in hot-melt extrusion-, and fused deposition modeling process, turned out to be challenging, but not impossible task. In conclusion, hot melt extrusion is a reliable method to produce polymer filaments for fused deposition modeling, that is suitable to print pharmaceuticals, however, the knowledge of this field is continuously expanding, thanks to the researchers around the world.
Microspheres are spherical particles containing the active substance, in our case bacterial probiotic strain Lactobacillus rhamnosus (L. rhamnosus), in an individually coated form. L. rhamnosus is a natural constituent of the human intestinal flora and is known to improve immune function, enhance healing of the intestinal mucosa, reduce inflammation, bloating and diarrhoea. The aim of our experimental work was to formulate sodium alginate microspheres containing L. rhamnosus bacterial strain as active ingredient and prebiotic (galactooligosaccharide, pectin, inulin). The microspheres were formulated using Büchi Encapsulator equipment, after which the entrapment efficiency was measured. The lyophilized product was filled into hydroxypropylmethylcellulose (HPMC) capsules and was subjected to a dissolution assay using Erweka equipment. The number of viable L. rhamnosus was determined from samples of the dissolution fluid. The microspheres are lyophilised to improve shelf-life and facilitate filling into traditional capsules. The number of viable bacteria in the lyophilizate was determined by inoculation on medium and standard microdilution test. Microspheres containing different compositions of pro- and prebiotics were formulated, and their antioxidant capacity was detected by 2,2-diphenyl-l-1-picrylhydrazyl (DPPH). We tested the anti-inflammatory effect of the microspheres using human IL-4 ELISA Kit on colon adenocarcinoma (CaCo-2) cell line.
Multiparticulate dosage forms are becoming more popular than single-unit forms because they offer benefits such as more consistent gastric emptying, a lower chance of dose dumping, and flexible drug release patterns [1]. Among the available production methods, extrusion-spheronization is preferred because it can handle high amounts of active ingredients without creating large particles, and it also allows for the easy combination of multiple drugs in one unit at any ratio [2]. The aim of this research is to determine the optimal parameters of the extruder, namely, the screw rotation speed, liquid addition rate and powder feeding rate, to determine the independent process parameters of the spheroniser, and to measure the loss-on-drying values, particle size distribution, and morphology of extrudates. The required machines to produce pellets are a twin-screw extruder, a spheroniser, a peristaltic pump, and a cooling system. Extrudates were obtained by using a mixture of microcrystalline cellulose, corn starch, lactose monohydrate and 10% povidone solution.
The use of batteries, found in telephones, remote controls, and medical devices, is an integral part of our daily lives. Unfortunately, the routine use of these electronic devices has harmful effects on the environment, primarily due to the pollution generated by heavy metals. This article traces the history of batteries, starting with the birth of the voltaic battery in 1799, invented by Alessandro Volta. This discovery, based on the principle of redox reactions between zinc and copper, was subsequently taken up and improved on numerous times. In 1836, John Frederic Daniell designed a two-compartment cell, stabilized by depolarizers and connected by a salt bridge. To meet today's climate challenges, researchers continue to design batteries, but this time they are biodegradable, edible, rechargeable, and therefore sustainable. In recent years, we have seen the emergence of highly innovative concepts. Some scientists, for example, are using cuttlefish ink to extract melanin. In a sodium-ion battery, this molecule acts as a natural anode, enabling sodium ions to be stored and thus contributing to the device's eco-friendliness. Other innovative research has also emerged, using other natural ingredients such as quercetin and riboflavin. These technological advances are of particular interest to the healthcare sector for the development of implantable medical devices.
The use of batteries, found in telephones, remote controls and medical devices, is an integral part of our daily lives. Unfortunately, the routine use of these electronic devices has harmful effects on the environment, not least because of the pollution generated by heavy metals. This article traces the history of batteries, starting with the birth of the voltaic battery in 1799, invented by Alessandro Volta. This discovery, based on the principle of redox reactions between zinc and copper, was subsequently taken up and improved on numerous times. In 1836, John Frederic Daniell designed a two-compartment cell, stabilized by depolarizers and connected by a salt bridge. To meet today's climate challenges, today's researchers are trying to design batteries that are biodegradable, edible and therefore eco-compatible. Some scientists, for example, are using cuttlefish ink to extract melanin. In this sodium-ion battery, this molecule acts as a natural anode, enabling sodium ions to be stored and thus contributing to the device's eco-friendliness. Other innovative research has also emerged, using other natural ingredients such as quercetin and riboflavin. These technological advances are of particular interest to the healthcare sector, for the development of medical devices.
3D printing is increasingly recognized as a versatile manufacturing approach, enabling the production of devices that are difficult or costly to fabricate using conventional methods. In this study, we aimed to develop a hollow, 3D-printed capsule designed for incorporation of a molten matrix containing an active pharmaceutical ingredient, and to evaluate its potential for gastric retention through controlled drug release. Capsule shells were fabricated from polylactic acid using fused deposition modeling and subsequently filled with polyethylene glycol-based melts. Micro-CT was employed to assess internal structure and integrity. Drug release profiles were measured for different matrix compositions, and texture as well as compositional analyses were performed on both filled and unfilled capsules. Our findings demonstrate that the 3D-printed PLA shells provide sufficient mechanical strength and, depending on the matrix composition, enable controlled, zero-order drug release for up to five hours. These results highlight the potential of 3D-printed capsules as a customizable, gastro-retentive drug delivery system, offering opportunities for personalized therapies.
This study focuses on the formulation and evaluation of a cream and gel containing niacinamide, a commonly used active ingredient in skincare. Niacinamide, a water-soluble form of vitamin B₃, is known for its ability to strengthen the skin barrier, reduce inflammation, and regulate sebum production. Two formulations were developed: a cream composed of cetyl stearyl alcohol, stearic acid, glycerol, isopropyl myristate, sucrose ester, propylene glycol, distilled water, and niacinamide; and a gel formulated with glycerol, carbopol, triethanolamine, distilled water, and niacinamide. The cream, an oil-in-water emulsion, was designed for rich, long-lasting moisturization, while the gel was intended as a lightweight, water-based alternative. Both formulations were analyzed for pH, texture, dissolution and potential toxicological properties. The results revealed distinct differences: the cream provided superior hydration and barrier repair, whereas the gel offered a non-greasy, refreshing texture more suitable for oily or combination skin types. These findings highlight the versatility of niacinamide in topical applications and establish a foundation for further research on its efficacy in different delivery systems.
Tumorous diseases are among the leading causes of death in the developed world, therefore there is a constant need for new antineoplastic medicines. In 2024, the EMA approved 28 anticancer drugs, of which 13 contains new active substances. In this review, we briefly summarize the mechanism of action and use of the new drugs approved by the EMA.
Plants produce a wide variety of secondary metabolites, many of which have complex structures. Wild and cultivated plants currently remain the primary sources of most pharmaceutically significant secondary metabolites. However, the production of these compounds in plants is limited by the capacity of their biosynthetic pathways. This limitation has prompted efforts to develop methods to increase the yield of desired secondary metabolites. Advances in "omic" techniques have accelerated the development of approaches that utilize plants as bio-factories to produce these valuable compounds. This review provides an overview of strategies for producing high-value plant products and using plants as heterologous hosts to produce foreign recombinant proteins for medical applications.
KRAS is one of the most frequently mutated oncogenes in cancer and is involved in various tumorigenic processes. Among its diverse roles, KRAS mutations have been shown to upregulate macropinocytosis, a form of endocytosis that allows cells to engulf extracellular fluid and its contained solutes, subsequently supporting the increased need for cancer cells' growth and proliferation. The nutrient uptake function of macropinocytosis was initially described within the framework of KRAS-driven pancreatic tumors. Although constitutive macropinocytosis can be induced by activating mutations of proteins that are commonly found in cancer, KRAS-induced macropinocytosis constitutes a fundamental area of research due to the high occurrence of mutated KRAS in cancer (~1/3 of all cancers). Furthermore, KRAS-mutated macropinocytosis not only contributes to tumorigenesis but also plays a critical role in developing resistance to treatments, as it was found to be implicated in Multi-Drug Resistance (MDR) in cancer cells. This mini-review aims to synthesize current knowledge of mechanisms of KRAS-mutated macropinocytosis briefly and examines the relationship between KRAS and macropinocytosis in the light of its role in cancer progression and drug resistance, highlighting therapeutic implications, targeting potential vulnerabilities and outlining clinical advancements in pertinent therapies.
The gut microbiota has become a central focus of research since its intricate connection with the brain was identified. Notably, the gut microbiota can influence mental health, opening new prospects for improving the management of psychiatric disorders. Understanding the bidirectional interactions between the brain, gut, and microbiome is crucial for evaluating the true impact of gut microbiota on mental health and its subsequent implications for psychiatry. Currently, the brain-gut-microbiome axis communicates through five interconnected pathways: the immune system, the vagus nerve, the enteric nervous system, the neuroendocrine system, and the circulatory system. The development of microbiota-based therapeutics signals significant changes in current clinical practices. Furthermore, microbiome-based therapeutics are expected to undergo substantial regulatory transformations in Europe in the coming years. This mini-review aims to explore these aspects to evaluate the potential of gut bacteria to shape mental health interventions.
Although a multitude of epidemics have already been eradicated with the use of modern antibiotics, in the 20th century, a new and increasingly serious phenomenon has arisen - the resistance against antibiotic therapies, necessiting the need for the development of novel antibiotic compounds. Transglycosylases are key enzymes in the biosynthesis of the bacterial cell wall, and currently there is no approved drug in human use against them, so they are an excellent target for further antibiotic development. During our research, the main goal was to synthesize compounds that are structurally similar to lipid ll, the substrate of bacterial transglycosylases, however, with significant modifications, such as the incorporation of an α-thioglycosidic unit instead of the α-O-glycosidic bond and an alkylphosphonate unit instead of the pyrophosphate part, making the molecules suitable to act as enzyme inhibitors. The key step of our work is the stereoselective construction of the 1,2-cis-α-thioglycosidic bond by photoinitiated thiol ene coupling reaction. ln this paper, the novel synthesis route is described which can be applied to furnish different lipid ll analogues, on example synthesis of a D-glucose derivative.
