Introduction: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that severely compromises quality of life. First-line therapy with 5-aminosalicylic acid (5-ASA) is limited by poor solubility, rapid absorption in the upper gut, and insufficient colonic delivery. Rectal formulations may overcome these issues, but conventional suppositories and enemas often reduce patient compliance.

Methods: Poloxamer 407 (P407)-based thermosensitive hydrogels were prepared using the cold method by dissolving the copolymer (20% w/w) in cold water and incorporating 5-ASA (0.1-0.5% w/w). The systems were characterized by rheological behavior, gelation temperature, mucoadhesive strength, injectability and spreadability. Drug release was evaluated at pH 5.0 and 7.4 by dialysis and membrane-less methods. Anti-inflammatory effects were tested in lipopolysaccharide -activated RAW264.7/Caco-2 co-cultures and in dextran sodium sulfate (DSS)-induced murine colitis model.

Results: The optimized P407-5-ASA hydrogel showed rapid gelation at physiological temperature, mucoadhesion, shear-thinning flow and easy syringeability, ensuring patient-friendly administration. 5-ASA showed prolonged release profiles even under acidic conditions. In vitro tests demonstrated that the formulation decreased both the macrophage infiltration and TNF-α secretion compared to free drug. Rhodamine-labelled gels demonstrated prolonged colon retention and P407-5-ASA markedly improved the therapeutic outcomes in DSS-treated mice with respect to commercial 5-ASA.

Conclusions: P407-based in situ hydrogels provide a high-performance, patient-acceptable platform for localized IBD therapy. They enhance 5-ASA efficacy and retention combining thermo-responsive gelation, mucoadhesion and sustained release while minimizing systemic exposure.

The obtained results support their potential as next-generation rectal formulations to improve the therapeutic outcomes and adherence in IBD patients.

Diketopiperazines (DKPs) are small, conformationally constrained cyclic dipeptides that have emerged as versatile scaffolds in drug discovery. Their rigid structures, chemical stability, and ability to mimic peptide backbones allow them to engage protein targets with high specificity, making them attractive candidates for receptor modulation. In particular, DKPs can overcome limitations of linear peptides, such as enzymatic instability and conformational flexibility, thereby offering improved pharmacological potential [1].

In this study, we investigated five Type 3 DKPs as potential modulators of Neurotensin Receptor 1 (NTSR1), a Class A G-protein coupled receptor (GPCR) implicated in neurological processes, pain regulation, and cancer progression [2]. The crystal structure of NTSR1 (PDB ID: 4GRV) was used as the receptor model, and molecular docking was performed with AutoDock 4.2 to assess peptide–receptor interactions [3]. All five DKPs demonstrated favorable binding energies, ranging from −4.31 to −7.83 kcal/mol, and engaged key residues within the orthosteric binding pocket. Notably, the compound HIJBAD exhibited the strongest predicted affinity (−7.83 kcal/mol), supported by a network of hydrogen bonding and hydrophobic interactions that suggest enhanced receptor stabilization.

These findings provide evidence that DKPs can serve as stable peptide-mimetic ligands capable of targeting GPCRs such as NTSR1. This work highlights their potential as chemical probes or lead scaffolds for the development of therapeutic agents in neurodegeneration and cancer. Further computational and experimental validation will be essential to fully establish their pharmacological relevance.

1. Bojarska et al., Biomolecules, 2021, 11(10), 1515. https://doi.org/10.3390/biom11101515

2. Huang et al., Nature, 2020, 579, 303–308. https://doi.org/10.1038/s41586-020-1953-1

3. Morris et al., J. Comput. Chem., 2009, 30, 2785–2791. https://doi.org/10.1002/jcc.21256

INTRODUCTION

Orally disintegrating tablets (ODTs) are popular due to their rapid disintegration, improved patient compliance, and enhanced therapeutic efficacy. Designing ODTs requires careful optimization of formulation variables to achieve desired quality attributes. This study integrates Central Composite Design (CCD) and Artificial Neural Networks (ANN) to optimize Doxylamine Succinate ODTs using binder and superdisintegrant variables.

METHODS

CCD was used to design and develop directly compressed Doxylamine Succinate ODTs. Binder concentration (Povidone) and superdisintegrant (Crospovidone) were the independent variables, with tablet friability, wetting time, and disintegration time as the dependent variables (responses). The compressed tablets were evaluated for all the responses. The dissolution studies were also performed in Hydrochloric Acid (0.01N). Response data were used to train the ANN-based model to optimize the formulation. ANN-based optimized formulation was assessed for drug release, and the release profiles of CCD and ANN-based optimized formulations were compared, using the f₂ test (similarity factor test).

RESULTS

All the CCD proposed formulations showed appropriate wetting time (10-12 seconds) with disintegration time ranging from 27-29 seconds and friability lower than 1%. All the formulations showed drug release above 80%. The highest drug release was observed with F7, which was considered the optimized formulation based on CCD results.

The selection of the optimal number of nodes influences the performance of the ANN model. The model for the current study was trained using the TanH values ranging from 3 to 10. The SSE and r² values were recorded at each node value. Node value 5 was the best activation node. The release profile of the ANN-optimized formulation was also assessed. The f₂ test demonstrated similarity between the two formulations.

CONCLUSION

The integration of ANN with CCD provides a robust, reliable, and multi-objective optimization platform for ODT development.

Introduction Neuroleptics are used as psychotropic medication for treatment of psychosis, schizophrenia, bipolar disorder, apathy and neurosis. The latest research on their biological activity shows their new activities including anticancer against brain, lung, breast, liver and colon cancer, antiviral against SARS-CoV and suppression of infections caused by dengue virus. Neuroleptics such as fluphenazine, triflupromazine and trifluoperazine were the research subject. The aim of the study was to synthesize new quinoline analogs of selected neuroleptics as new drugs’ candidates with more beneficial ADMET profiles.

Methods To synthesize new quinoline analogs, 6H-8-trifluoromethylquinobenzothiazine was synthesized by the reaction of 2-amino-4-trifluoromethylthiphenol with 3-bromo-2-chloroquinoline. After synthesizing 6H-8-trifluoromethylquinobenzothiazine its structure was confirmed by spectroscopic methods. Afterwards 6H-8-trifluoromethylquinobenzothiazine was used as a substrate to obtain new quinoline analogs with pharmacophore dialkylaminoalkyl substituents. The structure of each one of newly synthesized compounds was confirmed by the use of spectroscopic methods such as ¹H NMR, ¹³C NMR and ESI HR MS. All synthesized compounds were studied for anticancer activity against three human cancer cell lines: breast (MDA-MB-231), pancreatic (Mia-PaCa-2) and lung (A-549). Doxorubicin and cisplatin were used as reference drug. Human keratinocyte cell line (HaCaT) was used as healthy cells.

Results The research carried out allowed to synthesize 6H-8-trifluoromethylquinobenzothiazine and to obtain new quinoline analogs with pharmacophore dialkylaminoalkyl substituents. Currently, eleven new quinoline analogs were synthesized. The study for anticancer activity allowed to determine concentration of new compounds required for 50% inhibition of three human cancer cell lines.

Conclusions The method chosen to synthesize new quinoline analogs was effective and allowed eleven new compounds to be obtained. The study for anticancer activity against three human cancer cell lines concludes that there are three compounds that show the most promising anticancer activity (IC₅₀ < 5.5 μM).

Introduction

Psoriasis is a chronic, immune-mediated inflammatory skin disorder that demands effective and sustained therapeutic strategies. Conventional topical treatments often suffer from poor drug solubility, limited skin permeability, and systemic side effects. This study aimed to develop a novel Self-Microemulsifying Drug Delivery System (SMEDDS) incorporating lavender oil to enhance drug delivery and therapeutic efficacy for psoriasis management.

Methods

Comprehensive preformulation studies identified ethyl oleate as the oil phase, Tween 80 as the surfactant, and PEG 300 as the co-surfactant. A pseudo-ternary phase diagram guided the selection of an optimized oil-to-Smix ratio. The formulation was characterized for droplet size, zeta potential, and transmittance, and incorporated into cream bases with varying stearic acid concentrations. Analytical techniques including UV spectrophotometry and GC-MS validated the identity and purity of the drug and excipients. In vitro diffusion studies using Franz diffusion cells and cell line assays were conducted to assess drug release and biological activity. The HET-CAM assay was used to evaluate irritation potential.

Results

The optimized SMEDDS exhibited a droplet size of 147.3 nm, zeta potential of -26.1 mV, and transmittance of 92.57%, indicating a stable microemulsion. Among the cream formulations, the one with 10% stearic acid showed the best drug content and release profile. In vitro studies demonstrated sustained drug release over 24 hours, outperforming conventional formulations. Cell line studies revealed a 56% reduction in TNF-α expression and ROS reduction at 1 μg/mL, indicating strong anti-inflammatory potential. The HET-CAM assay confirmed the formulation’s non-irritating nature.

Conclusion

The developed lavender oil-loaded SMEDDS formulation significantly improved solubility, skin permeability, and controlled drug release, while demonstrating anti-inflammatory efficacy and safety. These findings support its potential as a novel, patient-friendly topical treatment for psoriasis.

The development of hybrid molecules that integrate distinct pharmacophores represents a valuable strategy in medicinal chemistry to enhance therapeutic potential. In this work, we describe the synthesis of 2-(4-isobutylphenyl)-N-(naphthalen-1-yl)propanamide, a novel amide derivative that combines the structural features of ibuprofen, a prototypical nonsteroidal anti-inflammatory drug (NSAID), with naphthalen-1-amine, an aromatic amine of pharmacological interest. The target compound was obtained via a single-step synthetic strategy employing dicyclohexylcarbodiimide (DCC) as a coupling reagent. Specifically, the carboxylic acid functionality of ibuprofen was activated in situ with DCC, enabling nucleophilic substitution by naphthalen-1-amine to afford the desired amide. The product was purified by recrystallization and chromatographic techniques, and its structure was confirmed using FTIR, ^1H NMR, ^13C NMR, and mass spectrometry.

This hybridization approach was designed to merge the anti-inflammatory pharmacophore of ibuprofen, known for cyclooxygenase (COX) inhibition, with the lipophilic naphthylamine scaffold, which could modulate binding interactions or pharmacokinetic behavior. The straightforward use of DCC-mediated amide bond formation demonstrates the efficiency of this method in generating novel derivatives without the need for multistep activation or protection strategies. While the current study emphasizes the synthesis and characterization of the compound, future investigations will explore its biological activity and potential improvements in anti-inflammatory efficacy compared to the parent drug.

According to the World Health Organization (WHO), more than 300,000 people die each year as a result of skin injuries, wounds, cuts or burns and auto immune diseases. Wound healing process is a complex biological process which involves several overlapping phases, hemostasis, inflammation, proliferation and remolding. Inflammation is the major phase of healing process which plays a crucial role for the startup of repairing process. Untreated wound care can lead to prolonged inflammation and complications. Already available skin dressings are dry in nature. These ordinary dressings do not maintain moisture at wound site and also does not deal with optimal wound healing process. Consequently microbial growth leads to pain in patients. In order to lessen side effects associated with ordinary dressings, transdermal hydrogel films of Moringa oleifera gum (2%) using Psidium Guajava extract (0-4 %) with 0.5% w/v calcium chloride as crosslinking agent were developed by solvent casting method through ionic interaction. First of all gum solution was prepared and dissolved in Polyethylene glycol as plasticizer. Afterwards extract solution was added dropwise and stirred for 15 minutes. Lastly solution was casted in petri dishes and allowed to dry. Higher swelling (%) was observed with formulation having 3 % of guava extract. Physicochemical properties and wound contraction studies were performed on hydrogel films having high mechanical strength and swelling index. The antibacterial activity against staphylococcus aureus causes an inhibition zone (2.9 mm ± 0.004) to form around the hydrogel films. No interaction among polymers and uniform surface morphology which support controlled drug release was observed with FTIR and SEM. In vivo wound healing studies on rats showed 85 % w/w of percentage wound contraction to treat wound within 10 days. Fabricated polymeric hydrogel films were effective bioactive wound dressings due to their significant anti-bacterial activity, high biocompatibility and wound healing efficacy.

Despite significant progress in medicine, cancer continues to be one of the leading causes of death worldwide. Since the discovery of cisplatin's antitumor activity, it has remained one of the most commonly used chemotherapeutics in cancer treatment (1). However, serious side effects of platinum-based drugs significantly limit their clinical use. The study of transition metal complexes and their biological properties (e.g. antimicrobial, cytotoxic, anti-inflammatory, interactions with DNA) are the subject of intensive studies (2). Copper and zinc complexes, as an alternative to platinum-based drugs, display notable anticancer activity while causing fewer side effects than cisplatin. The variation in their biological activity is associated with the molecular structure of the ligand, and the type of central metal ion. Complexes of the salen-type ligands represent a promising group of compounds in medical research. Since colorectal cancer is the third most diagnosed type of cancer, the aim of this work was to prepare and study the antitumor effect of Schiff base ligands derived from 1,2-cyclohexanediamine and fluorine-substituted benzaldehydes and their Cu(II) and Zn(II) complexes (3,4). All derivatives were examined for their antitumor activity against two model human colorectal adenocarcinoma cell lines (HT-29 and Caco-2) by MTT assay. Experimental results showed that in comparison with cisplatin, the studied Cu(II) and Zn(II) complexes can significantly inhibit the growth of both HT-29 and Caco-2 tumor cells. Due to their marked cytotoxic effect, these metal complexes represent a promising alternative for the development of new anticancer agents.

This research was supported by grant APVV-23-0349.

1. R. Oun et al. Dalton Trans 47, 2018, 6645.
2. A. Temesgen et al., ChemistrySelect 8, 2023, e202302113.
3. B. Oboňová et al., Life 13, 2023, 1516.
4. B. Oboňová et al., Int. J. Mol. Sci. 25, 2024, 9166.

Chronic Myeloid Leukemia (CML) progression from chronic phase (CP) to advanced stages such as accelerated phase (AP) or blast crisis (BC) remains a major clinical challenge, particularly due to limited early detection biomarkers. In this study, we investigate the genetic mutations driving CML progression, focusing on the MUC3A gene and the downstream regulatory region of the MIR5195 gene. We identified a novel missense mutation, P258S, in MUC3A that is exclusively present in AP/BC-CML patients. Structural and physicochemical analyses revealed that the P258S mutation alters protein stability, increasing flexibility in some regions and stabilizing others, which may affect its molecular interactions. Molecular dynamics simulations and docking studies showed enhanced binding affinity of MUC3A P258S with several therapeutic agents, particularly Capmatinib, suggesting potential clinical applications in treating CML. Additionally, mutations in the MIR5195 regulatory region were found to disrupt transcription factor binding, leading to changes in gene expression patterns. MEME and TOMTOM motif analysis revealed the loss of key motifs and the emergence of new ones in the mutant sequences, indicating a shift in the transcriptional regulation landscape. These findings suggest that these mutations may influence the expression of genes involved in CML progression. This study highlights the potential of MUC3A and MIR5195 as biomarkers for CML progression and therapeutic targets for personalized treatment strategies. The identified P258S mutation in MUC3A opens new avenues for targeted therapies, while the regulatory alterations in MIR5195 offer insights into gene expression reprogramming in CML's advanced stages.

Introduction: Antibiotic resistance is recognized as a major public health threat. Antimicrobial peptides provide an alternative to antibiotics. Human β-defensin 1 (hBD1), produced by epithelial cells, demonstrates broad antimicrobial activity and retains stability after proteolysis. However, its clinical application is constrained by high synthesis costs. This study aimed to generate a eukaryotic cell platform for hBD1 expression and secretion.

Methods: Plasmids pHBD1-Out and pHBD1RFP-Out were designed using the pcDNA3.1(+) vector with the CMV promoter. Cloning was performed in E. coli XL1-Blue, followed by plasmid purification and restriction analysis. HEK-293T cells were transfected via lipofection. Transfection efficiency was evaluated after 48 h by fluorescence microscopy. hBD1 production was confirmed by PAGE and HPLC. Antimicrobial activity was assessed against E. coli using agar diffusion assay.

Results: The pHBD1-Out plasmid carried the hBD1 sequence and the SRP9 signal peptide for extracellular expression, while pHBD1RFP-Out additionally contained A2P peptide and RFP marker. Transfection was confirmed by the presence of fluorescent cells, although the efficiency was relatively low. hBD1 production was detected in both cell lysates and supernatants, showing similar expression patterns for pHBD1-Out and pHBD1RFP-Out. Lysates demonstrated pronounced antimicrobial activity comparable to ampicillin. Supernatants also inhibited E. coli growth, though less effectively.

Conclusions: The constructed plasmids enabled efficient hBD1 expression in HEK-293T cells. The recombinant peptide exhibited antimicrobial activity comparable to conventional antibiotics, highlighting the potential of cell-based systems for AMP production and the development of novel antimicrobial therapeutics. This work was supported by the Ministry of Science and Higher Education of the Russian Federation in 2025 (No. 0088-2025-0004).