Uterine fibroids are a prevalent clinical concern in gynecology, and current surgical interventions, myomectomy and hysterectomy, pose risks of complications and potentially compromise reproductive function. Given the limitations of conventional treatments, there is a significant need for organ-sparing alternatives, such as gene therapy.
This study addresses the development of non-viral gene delivery strategies for uterine fibroids. Traditional viral vectors present substantial risks, including immunogenicity, insertional mutagenesis, and limitations in repeated administration. Non-viral systems for uterine fibroid therapy remain relatively unexplored despite their potential for localized treatment and reduced systemic effects.
We developed a novel ternary peptide-based system incorporating both cationic and anionic peptide components to address limitations of conventional binary complexes. The inclusion of anionic peptides enhances complex stability via improved charge distribution, promotes efficient cellular internalization, and reduces nonspecific interactions with biological constituents. Our optimization strategy focused on two key parameters: minimizing complex formation volume while maintaining therapeutic DNA payload, and determining optimal charge ratios between DNA, cationic and anionic peptides.
Comprehensive physicochemical characterization included analysis of hydrodynamic properties via dynamic light scattering (DLS), surface charge assessment via zeta potential measurements, DNA binding capacity evaluation, and investigation of release kinetics. Biological evaluation demonstrated preserved cellular viability and significantly enhanced transfection efficiency in both cell culture models and ex vivo fibroid tissue. The system achieved consistent particle sizes below 200 nm with favorable surface charge characteristics for cellular uptake.
These findings suggest that this optimized ternary peptide system represents a robust and efficient platform for gene delivery to uterine fibroid cells, offering a promising organ-preserving approach for translational gene therapy applications.

Persistent Human Papillomavirus (HPV) infections can progress through a multistep carcinogenesis process, ultimately leading to invasive cancers. Imiquimod (IQ), a topical agent with antiviral and antitumoral properties, has shown promising outcomes in HPV-related pre-malignant lesions and even oral cancer case reports; however, its clinical application remains limited by poor solubility and low tissue selectivity. To overcome these challenges, nanoparticle-based systems such as liposomes, widely recognized for their safety and effectiveness in drug delivery, represent a promising strategy to enhance IQ therapy for oral cancers. Functionalization with targeting ligands may further enhance their selectivity. In this context, the nucleolin-binding aptamer AT11, which folds into a G-quadruplex structure, represents a valuable targeting moiety to promote selective drug accumulation in cancer cells.

Empty or IQ-loaded liposomes were prepared by the ethanol injection method and subsequently functionalized with AT11-TEG-Cholesteryl, yielding nanoparticles with hydrodynamic diameters of ~120-140 nm, and with %EE of ~83%. Their biological performance was assessed in squamous cell carcinoma of the tongue (UPCI-SCC-154) and non-malignant esophageal epithelial (Het1A) cells. Regarding their biological potential, AT11 IQ-associated liposomes allowed a selective delivery of IQ towards a tongue cancer cell line relative to the non-malignant cell line. Specifically, they induced a selective reduction of cell viability, proliferation and increased cell death. Additionally, they decreased the migration and invasion capacities of the cancer cells.

Overall, these findings highlight AT11-functionalized liposomes as a promising nanocarrier to improve the IQ selectivity and anticancer potential.

Acknowledgements:

Carla Cruz acknowledges the project Oralcare (ref. 12111309) winner of the UBI-CGD Innovation Award 2024, funded under the UBI-CGD 2023 Multiannual Patronage Agreement established between Caixa Geral de Depósitos and UBI, and also the “Projetos de Ignição e Provas de Conceito INOVC+”

Diabetic wounds represent one of the most serious complications of diabetes mellitus, often leading to delayed healing and increased risk of infection. Conventional therapies are limited in efficacy, which necessitates the development of novel therapeutic strategies. In this study, we aim to design and evaluate a sinensetin-loaded hydrogel formulation for the management of diabetic wounds, applying the principles of Quality by Design (QbD) to optimize its development. Sinensetin, a pentamethoxyflavone found in the leaves of Orthosiphon aristatus (Cat’s whiskers) and citrus fruit peels, has been reported to possess strong antioxidant, anti-inflammatory, and antimicrobial properties, making it a promising candidate for wound healing applications. The hydrogel will be formulated and characterized through advanced techniques, including FESEM, FT-IR, XRD, DSC, TGA, viscosity, pH, spreadability, in vitro drug release, entrapment efficiency and texture analysis. In vitro studies will be performed to assess antioxidant, antimicrobial, and anti-inflammatory activities. For in vivo evaluation, diabetes will be induced in rats using a high-fat diet (HFD) combined with a low-dose STZ injection, followed by excision wound creation. Percentage wound contraction, re-epithelialization, collagen deposition, biochemical study and histopathological features will be studied alongside molecular assays of inflammatory cytokines and growth factors. This work is expected to provide scientific evidence for the wound healing efficacy of sinensetin hydrogel, highlighting its potential as a novel therapeutic approach for diabetic wound management.

Introduction: Oncological therapies (radiotherapy/chemotherapy) often impair the skin barrier, leading to erythema, dryness, and inflammation. These changes make conventional topical formulations unsafe, as they may provoke irritation or cause uncontrolled drug penetration, resulting in either toxic or sub-therapeutic exposure. Multiple water-in-oil-in-water (W/O/W) emulsions offer a promising solution, providing controlled release, drug stabilisation, and better tolerability for fragile, inflamed tissue. Emulsion complex structure (aqueous droplets within larger oil drops) enables modulation of drug transport across damaged skin. Methods: Sodium diclofenac was encapsulated in W/O/W emulsions. Emulsion characterisation included diclofenac encapsulation efficiency, droplet size, three-month stability, and rheological behaviour. Transdermal delivery was evaluated in Franz diffusion cells using synthetic membranes and skin models subjected to UV-irradiation or cytostatic-induced inflammation to simulate post-therapy conditions. Drug concentration was quantified spectroscopically. Fibroblast viability was assessed with PrestoBlue assay. Results: Emulsions exhibited high encapsulation efficiencies (70.3±0.7% - 95.8±0.7%), droplet diameters of 15.1±0.5 – 22.5±0.9 µm, less than 15% size variation during storage, and showed shear-thinning behaviour consistent with the Power law model (consistency indices: 0.363–0.480 Pa·sⁿ; flow indices: 0.640–0.682; R² > 0.99). Damaged skin models displayed markedly increased and irregular permeability; conventional diclofenac formulations penetrated excessively and intensified irritation. In contrast, W/O/W emulsions provided modulated release, maintained therapeutic concentrations of drug. Fibroblasts exposed to UV/cytostatic damage showed >25% higher survival with diclofenac-loaded emulsions compared to standard solutions, indicating protective and regenerative potential. Conclusions: W/O/W emulsions represent a rational approach to transdermal delivery of anti-inflammatory drugs in oncology patients with impaired skin barrier. By ensuring controlled release and enhanced tolerability, they improve the safety of topical therapy.

The research was financially supported by the Warsaw University of Technology under the IChem-2025 grant from the Scientific Council of Chemical Engineering.

Purpose

This research aims to develop a stable Nanoemulsion formulation for a challenging, water-insoluble, and thermally, oxidatively, and photolytically unstable active pharmaceutical ingredient (API) for ophthalmic use, specifically to help reduce intraocular pressure (IOP) and provide neuroprotection. The cannabinoid API has shown great potential in treating glaucoma by targeting the endocannabinoid system (ECS) to lower IOP and provide valuable neuroprotection.

Method

The solubility of the cannabinoid in various oils was systematically assessed. Placebo trials were conducted to identify the appropriate stabilizer and its concentration. To mitigate oxidation, low peroxide-grade sesame oil, and nitrogen/argon-purged water were used throughout the process. Nanoemulsion was prepared under a nitrogen atmosphere. Reduction of particle size was accomplished utilizing a Microfluidics M110-P under optimized pressure and number of passes. Antioxidants were evaluated to inhibit the oxidation of the API. Various packaging materials were evaluated for stability.

Results

Sesame oil exhibited the most pronounced solubilizing capability for the API. Tween 80 effectively stabilized the Nanoemulsion, resulting in a particle size of approximately 150 nanometers. Treatment via a microfluidizer at a pressure of 25,000 PSI over five passes yielded the targeted particle size alongside a low polydispersity index and a narrow size distribution. The Nanoemulsion retained its particle size even after filtration through a 0.22 µm filter, experiencing minimal resistance. A synergistic combination of butylated hydroxyanisole /butylated hydroxytoluene and Vitamin A effectively mitigated the oxidation of the cannabinoid API. Containers composed of low-density polyethylene and high-density polyethylene demonstrated enhanced stability in comparison to polypropylene and amber glass containers.

Conclusion

This research proficiently formulated a stable Nanoemulsion for the ophthalmic delivery of the cannabinoid API, effectively mitigating issues related to its inadequate aqueous solubility and inherent instability. The findings provide valuable insights into the potential treatment of glaucoma using this novel Nanoemulsion formulation.

Nanosystems are gradually being more commonly used in a variety of applications, providing a new approach to therapeutics by improving the pharmacokinetic profile of several compounds. This has led to an increase in the search for bioinspired and sustainable materials for novel nanotechnology-based formulations with pharmaceutical and cosmetic purposes. For the delivery of bioactives to the skin, lipid nanoparticles, such as solid lipid nanoparticles (SLNs), have been thoroughly investigated. Their use is still being hampered, nevertheless, by issues with stability and drug loading during storage. Several methodologies, including the applicability of ionic liquids (ILs), may be used to improve this. These have proven to be a potential strategy due to the beneficial qualities that our group identified in earlier work, namely their capacity to enhance the colloidal stability of formulations. Using two different commercial lipids (Gelucire^R 43/01 vs. Precirol ATO^R 5) and an amino acid-based IL (2-hydroxyethyl)-trimethylammonium-L-phenylalaninate [Cho][Phe], this study aimed to assess the impact of the incorporation of the IL into the SLN, comparing both commercial lipids. After conducting stability tests and characterising these nanosystems in terms of size, zeta potential, and polydispersity index, SLNs with favourable properties were produced. The findings demonstrated that ILs helped to stabilise the nanoparticles and enhance their physicochemical characteristics for topical use. All things considered, choline-based ILs in combination with the creation of novel lipid nanocarriers from sustainable and bioinspired materials appear to create a new paradigm for skin delivery. These findings demonstrate that ILs can alter SLN size, which might enhance their physicochemical characteristics for topical use.

Metronidazole (MTZ) is a nitroimidazole antimicrobial widely used to treat various anaerobic bacteria and protozoa infections. MTZ is a small lipophilic molecule with an oral bioavailability higher than 90 %. An analytical theoretical-experimental solvatochromic study of MTZ that improves its pharmacokinetics understanding has not been done yet. To this research, twelve pure solvents: two non-polar, six polar aprotic, four polar protic, and buffer pH 7.4 were chosen. The spectrophotometric study was performed with 1x10^-5 M MTZ solutions. The TD DFT B3LYP and CAMB3LYP with the PCM in its IEFPCM formalism and the 6-311+G(d,p) basis set were used to obtain the MTZ UV-Vis theoretical spectra. Kamlet and Taft, Catalán and Laurence multiparametric equations were utilized to analyze the effect of the solvent environment on MTZ. These analyses exhibit positive solvatochromism. The mayor Kamlet and Taft's relative contribution was from non-specific π interactions, accounting for 65 %. Catalán and Laurence equations showed that these non-specific contributions were mostly due to polarizability and dispersion forces (65 % SP and 72 % DI). While hydrogen-bond specific interactions were much less relevant: 35 % β, 16 % SB, and 20 % β₁. All calculated maximum wavelengths, which correspond to the electronic transitions of the second singlet states for MTZ, were from HOMO to LUMO. These results show that polarizability rises significantly in polar solvents, reflecting enhanced electron cloud distortion, besides the high polarity of MTZ. Greater polarizability typically correlates with increased permeability through biological membranes, as the molecule can interact more effectively with the lipid environment and adapt to changes in polarity between the aqueous medium and the lipid bilayer membrane. This evidence could explain the easy penetration of MTZ into the microorganism cell by passive diffusion.

Physiologically based pharmacokinetic (PBPK) modeling serves as an important tool in drug development and personalized therapy. It enables the integration of individual patient physiological characteristics to predict drug distribution across tissues, which is particularly relevant for chronic diseases, impaired liver and kidney function, as well as for off-label application scenarios or evaluation of new compounds.

This work presents an interactive PBPK model that describes drug distribution across 13 major body compartments: blood, liver, kidneys, lungs, heart, muscle and adipose tissue, brain, bones, gut, spleen, skin, and other tissues. The model is based on systems of ordinary differential equations (ODEs). Key pharmacokinetic parameters are incorporated in the calculations: some are determined experimentally (e.g., logP, unbound drug fraction, hepatic clearance), while others are obtained from literature sources (e.g., pKa).

A distinctive feature of this development is its complete implementation within the open-source R environment using the deSolve package for numerical integration of equations. This approach ensures full transparency, reproducibility of results, and easy integration with other statistical and bioinformatic tools. The model is integrated with an intuitive Shiny/plotly web interface, allowing flexible adjustment of administration route, organ clearance, dosing regimen, and frequency.

As a case study, simulations were performed for azemiopsin - a peptide neurotoxin with muscle relaxant properties. The model demonstrated pronounced drug accumulation in muscle tissue with rapid clearance from systemic circulation. An additional module simulated antibody-antigen interaction, which is considered and modeled within the framework of the drug-drug interaction (DDI) concept. This demonstrates the platform's capability to analyze complex pharmacokinetic scenarios and various dosing regimens.

The PBPK model shows high flexibility and practical value. It can be used for planning preclinical studies, optimizing experimental protocols, refining ADME profiles, and predicting individual body responses to drugs, thereby creating a foundation for personalized pharmacotherapy.

Introduction: Voacanga africana is a widely used medicinal plant in Africa for the treatment of several diseases, including mental disorders. This study investigated the ADME properties and inhibitory potential of compounds detected in the roots of the plant on acetylcholinesterase (AChE) and monoamine oxidase B (MAO-B), targets implicated in neurological disorders.

Methods: The roots of V. africana were extracted with 80% methanol, after which the extract was subjected to UPLC-ESI-MS/MS in negative mode. Known compounds were docked against AChE and MAO-B obtained from the Protein Data Bank (PDB ID: 4EY7 and 4A7A, respectively), using AutoDock. Drug likeness and ADME prediction were achieved using SwissADME and vNN-ADMET online servers, respectively. Rivastigmine and Rosiglitazone were used as the standard inhibitors of AChE and MAO-B, respectively.

Results: Some of the compounds had higher binding affinities against AChE and MAO-B compared to the standards, which had binding affinities of -8.0 and -9.8 kcal/mol, respectively. The top five compounds inhibited both targets with binding affinities of -12.4 to -9.6 kcal/mol for AChE and -12.1 to -10.2 kcal/mol for MAO-B. They include tsangibeilin B, rel-, Elisabatin B, Pinocembrin 7-[4-(1-hydroxyethyl)phenyl] ether, Hedyotol C and obochalcolactone. Tsangibeilin B, rel- had the highest binding affinity for both targets. It exhibits desirable drug-likeness properties, acts as a P-glycoprotein inhibitor and substrate, permeates the blood-brain barrier, is stable with respect to the human liver microsomal stability assay, and does not inhibit cytochrome P450 enzymes.

Conclusion: The top-scored compounds, especially tsangibeilin B, rel- therefore, pose as potent inhibitors of AChE and MAO-B, demonstrating their potential in neurological disorders..

Kojic acid (KA), a natural compound with notable biological properties, is a versatile scaffold (5-hydroxy-2-(hydroxymethyl)-4H-pyran-4-one) for developing novel therapeutic agents. This study aimed to synthesize KA-based derivatives and evaluate their multifunctionality as anti-tyrosinase, anticancer, antioxidant, and anti-malarial agents. Exploring KA derivatives holds promise for advancing in skin brightening, malaria, and cancer therapeutics, and managing oxidative stress, addressing the demanding need for multifunctional compounds in modern medicine. KA derivative (DRC-01) was synthesized through one-pot aldol condensation chemical reactions and structurally confirmed using advanced spectroscopic techniques, including FTIR, NMR, and mass spectrometry. The anti-tyrosinase activity on Mushroom Tyrosinase protein from RCSB PDB (PDB: 2Y9X) and anticancer potential were evaluated in vitro using the MTT assay against human cancer cell lines: HCT-116 (colon cancer), PANC-1 (pancreatic cancer), MDA-MB-231 (triple-negative breast cancer), and MCF-7 (hormone-responsive breast cancer). Antioxidant activity was assessed using the DPPH assay to determine radical scavenging properties, and the Antimalarial activity was performed by SYBR GREEN assay in Plasmodium falciparum 3D7. DRC-01 showed binding energy -7.4kcal/mol compared to standard KA -5.8kcal/mol and dose-dependent cytotoxicity, demonstrating anticancer activity at higher concentrations (>50 µM) across all tested cell lines. Additionally, DRC-01 displayed moderate radical scavenging activity in the antioxidant assay, and Antimalarial potential was at IC₅₀ = 54.94±3.11µg/mL. These findings highlight that DRC-01 could be a candidate for therapeutic applications with its cosmeceutical properties. Further structural optimization is acceptable to enhance their potency and selectivity, reinforcing their value in the fight against cancer, malaria, and oxidative stress-related disorders.