Background and Objectives:
Lidocaine hydrochloride (LD-HCl) is the most widely used local anesthetic in dentistry, commonly combined with epinephrine to prolong anesthesia and limit systemic absorption. However, its short duration of action, need for repeated injections, and bitter taste often reduce patient compliance and procedural efficiency. This study aimed to develop and evaluate an injectable in-situ forming nanoemulsion-based gel depot system of LD designed to provide sustained anesthetic activity.Methods:LD nanoemulsions were prepared by high-shear homogenization followed by probe sonication using Miglyol 812 N (oil phase), Tween 80 and soy lecithin (surfactant–co-surfactant), glycerin, and deionized water (aqueous phase). The optimized formulation (S1) was incorporated into a thermoreversible poloxamer solution to yield a nanoemulgel. The formulation was evaluated for particle size, distribution, zeta potential, morphology, pH, drug content, stability, rheology, injectability, and in vitro release. Analgesic efficacy was assessed in Wistar rats by tail-flick and paw withdrawal latency tests, while cardiovascular safety was monitored using non-invasive electrocardiography and blood pressure measurements.Results:The optimized nanoemulsion exhibited spherical morphology with a mean particle size of 206 nm, high negative zeta potential (-66.67 mV), and narrow distribution (PDI ≈ 0.40). The nanoemulgel demonstrated desirable thixotropic behavior, ensuring ease of injection. In vitro release studies showed sustained lidocaine release for 5 hours, following the Higuchi model. In vivo, the nanoemulgel significantly prolonged analgesia, lasting up to 150 minutes (2.5 h) compared with conventional LD-HCl injection (p < 0.001). No adverse cardiovascular effects were observed.Conclusions:
The developed LD-loaded in-situ nanoemulgel offers a promising and patient-friendly alternative for dental and minor surgical anesthesia. By extending anesthetic duration, it reduces the need for repeated injections, improves patient comfort, and enhances procedural efficiency.

Naproxen, a widely used non-steroidal anti-inflammatory drug (NSAID), is effective in managing musculoskeletal inflammation but is often associated with gastrointestinal side effects and hepatic first-pass metabolism when administered orally. To address these limitations, this study focused on developing and comparing two advanced vesicular drug delivery systems “Transethosomes and Transniosomes” incorporated into emulgels for transdermal delivery of Naproxen. These vesicular systems enhance skin permeation and offer fast release, making them promising candidates for topical NSAID delivery.
A 2-factor, 3-level experimental design was employed to optimize formulation parameters. Naproxen-loaded Transethosomes and Transniosomes were prepared using the thin-film hydration method and subsequently incorporated into hydroxypropyl methylcellulose (HPMC)-based emulgels. The resulting emulgels were evaluated for pH, viscosity, spreadability, FTIR interactions, and in vitro drug release behavior. Optimized formulations, designated TE7 and TN1, exhibited high entrapment efficiency, appropriate vesicle sizes, and desirable physical characteristics. FTIR analysis confirmed compatibility between Naproxen and formulation excipients.
In vitro drug release studies demonstrated efficient Naproxen release, with the Transethosomal formulation (TE7) showing a slightly faster release profile compared to the Transniosomal formulation (TN1). These findings suggest that both emulgel systems offer promising potential as effective transdermal alternatives to conventional oral NSAID therapy for musculoskeletal conditions, potentially improving patient compliance and minimizing systemic side effects.

Introduction and Background: Multidrug resistance (MDR) is a major obstacle in cancer treatment, often caused by the action of permeability glycoprotein (P-gp) efflux pumps which reduce drug accumulation in cancer cells. To develop and optimize a nanoformulation of Irinotecan using excipients known for their P-gp inhibitory potential, aiming to overcome MDR in cancer therapy.

Methods: Nanoparticles were prepared and optimized employing a 3-factor, 2-level factorial design focusing on hydroxypropyl methylcellulose (HPMC) concentration and the number of preparation cycles. Particle size, polydispersity index (PDI), and entrapment efficiency were evaluated. Characterization was performed using Differential Scanning Calorimetry (DSC) and X-Ray Diffraction (XRD) to confirm molecular dispersion. In vitro P-gp inhibition was assessed in Caco-2 cells with ELISA analysis, and in vivo efficacy was evaluated through pharmacokinetic studies in rats.

Results: The optimized Irinotecan nanoparticles exhibited a particle size of 201 nm, PDI of 0.100, and entrapment efficiency of 91%. DSC and XRD confirmed the molecular dispersion of the drug within the freeze-dried nanoparticles. In vitro studies demonstrated significant P-gp inhibition, with the nanoformulation requiring nearly half the concentration to achieve similar effects compared to the free drug. In vivo studies showed enhanced P-gp inhibition, indicated by improved maximum plasma concentration (Cmax) values.

Conclusion: Excipients-based Irinotecan nanoparticles effectively inhibit P-gp activity, providing a promising nanoformulation strategy to overcome multidrug resistance in cancer treatment.

Photoallergy can be considered a special type of contact hypersensitivity, in which UV light activates the allergen and, therefore, the physiological mechanisms involved in the development of symptoms. In the case of pharmaceuticals, preclinical trials should include phototoxicity and photoallergy assays to ensure their safety. However, nowadays there is still a lack of non-animal methods to predict potential photoallergic reactions. Knowledge of the pathophysiological mechanisms of photoallergic contact dermatitis at different levels, such as molecular and cellular ones, is thus an important field of research. In this sense, this work explores the use of a cell line of skin keratinocytes to develop a vitro assay to identify phototoxic molecules and discriminate between phototirritant and photoallergic by differential secretion of humoral molecules. To achieve this goal, keratinocytes have been exposed to different chemicals at various concentrations with well-known phototoxic potential concomitantly with 4 J/cm² UVA or maintained in dark. The chemicals assayed were Chlorpromazine (photoirritant and photoallergen); 8-methoxypsoralen (photoirritant); Benzophenone (photoallergen) and p-phenilendyamine (allergen). After 24 hours post-incubation cell viability was determined and the concentration that induces an 80% of cell viability in dark and UVA conditions was calculated. Then, the secretion of different metalloproteinases (10) and inflammatory cytokines (40) in supernatant was evaluated by semi-quantitative arrays (RayBiotech). Our results indicate that MMP-1 and IL-6 are potential biomarkers to discriminate between photoirritant and photoallergic reactions. Next step includes to evaluate the release of both biomarkers with a more quantitively assay as ELISA and increasing the number of chemicals studied.

Acknowledgement: Grant PID2020-113186RB-I00 funded by MCIN/AEI/10.13039/501100011033

HDAC4 is a class IIa member of histone deacetylases (HDACs), playing a role in regulating gene expression through chromatin remodeling, as well as in muscle alterations. It triggers the atrogin-1 and MuRF1 upregulation, muscle protein degradation, and slow atrophy progression, symptoms associated with Spinal Muscular Atrophy (SMA), for which it is considered an important target for corresponding palliative care therapeutic development.

In that sense, our interests were to develop selective PROTAC degraders of HDAC4 using known co-crystalized HDAC4 inhibitors (HDAC4Is) available at Protein Data Bank as starting points, particularly the truncated version of 6FYZ HDAC4I as a warhead stripped of the Cap moiety, as instructed by the generated preliminary Py-CoMFA 3-D QSAR model. The primary objective during the initial profiling phase was to investigate their interactions with HDAC4 and assess how structural modifications influence potency. To that, the PROTACs were initially autonomously designed by means of Python’s RDKit by merging the warhead with the in-house available linkers and either VHL-1 or CRBN E3 ligase ligands, respecting the desirable PK/PD profiles. Selected hits were promptly synthesized and submitted to enzymatic fluorogenic assaying, of which TG-49 and PJ594, as VHL-1-related PROTACs, showed remarkable IC₅₀s of 50 and 150 nM. Regarding the whole panel, interestingly, even minor changes in the linker structure resulted in significant variations in the inhibition of HDAC4, suggesting that the linker may play a critical role in mediating interactions with HDAC4. Yet, confirmation is pending with further ternary complex computational modeling and HDAC4 cellular degradation assays.

Wound healing is complex process and is subject of intense research. Use of plants against diseases is in practice from decades. In present study, green ZnO NPs dressings has been evaluated for antibacterial (in vitro analysis on Bacillus subtilis, Lactobacillus acidophilus, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Klebsiella aerogenes), hemolytic (in vitro), cytotoxic activity (MTT assay), water-solubility, biodegradability, capability to absorb large amounts of wound exudates and in vivo activity (on albino rats of both genders against incisionwounds). SEM confirmed successful incorporation of ZnO NPs into dressings. Broad peak at 3307 cm⁻¹ corresponded to O-H stretch in FTIR spectra, with new absorption peaks at 1600, 2000, and 2500 cm⁻¹ while intensity of C-O stretch was reduced which confirmed the degradation of dressings. ZnO NPs bandages contributed to high-water uptake, minimum hemolytic activity (19.8±0.88%) towards human RBCs at lowest dose (125μg/mL), decrease in HepG 2 cells viability with increased ZnO NP concentration, maximum inhibition of L.acidophilus (24±0.94 mm) and minimum activity against K.aerogenes (8±0.01 mm). On day 7, 60µg/mL of ZnO NPs embedded bandage showed highest healing activity in female rats (57.5%) as compared to male rats (45%), followed by bandage with 20µg/mL ZnO NPs (15% and 25 % healing in female and male rats). After 14 and 21 days, bandage with 10µg/mL nanoparticles showed 87.5% and 82.5% healing in male and female rats and 90% wound closure in both genders respectively. Bandage without nanoparticles, with PV and with 30µg/mL-50µg/mL nanoparticles showed lesser healing activity. Histological analysis of paw skin showed no inflammation but with reepithelization, collagen deposition, granulation tissue fibroblast maturation and neovascularization by bandage which was coated with least amount of green nanoparticles. Outcomes of current work indicate a clear improvement over conventional dressings and warrant further exploration of their unique properties for enhanced wound healing in clinical settings.

Among Chalcogen elements, sulfur, selenium, and tellurium, occupy a central position in both nature and synthetic chemistry. Their unique electronic structures give rise to diverse bonding patterns and reactivity, making them indispensable in biological systems and highly attractive in molecular design. Sulfur, for example, is a fundamental component of amino acids, cofactors, and signaling molecules, while selenium plays critical roles in antioxidant enzymes and redox regulation. Tellurium, although less common in biology, has recently emerged as a promising element for creating molecules with distinctive pharmacological and physicochemical profiles. These intrinsic properties explain why chalcogen chemistry has become an increasingly powerful tool for medicinal chemists seeking innovative solutions. In this way, incorporating chalcogen elements into organic frameworks has emerged as a versatile approach for generating novel compounds with significant potential in medicine and materials science. This presentation will highlight our recent efforts on the synthesis of selenium-, sulfur- and tellurium-functionalized molecules as a powerful tool in drug discovery. Recent advances in sustainable synthetic methodologies have made the incorporation of chalcogen atoms more accessible, enabling the design of innovative molecular scaffolds with therapeutic relevance. By showcasing representative examples and future perspectives, I aim to illustrate how chalcogen chemistry can expand the medicinal chemist’s toolbox and inspire the development of next-generation drugs.

Background:
Accurate and validated bioanalytical methods are essential for drug quantification in biological matrices to support pharmacokinetic and therapeutic drug monitoring studies. Palbociclib, Ribociclib and Letrozole are clinically relevant drugs; however, to date, no simultaneous bioanalytical method has been reported for their estimation in human plasma using HPLC-UV.

Materials and Methods:
A simple and sensitive high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed and validated for simultaneous determination of Palbociclib, Ribociclib and Letrozole in spiked human plasma. Sample preparation was performed using protein precipitation with acetonitrile. Separation was achieved on an Orochemorosil C18 column (250 × 4.6 mm, 5 µm) using a mobile phase of phosphate buffer (pH 3.0, 10 mM) and acetonitrile (60:40, v/v) at a flow rate of 1.0 mL/min. Detection was carried out at 260 nm.

Results:
The method was linear over the ranges of 10–300 ng/mL (Palbociclib), 10–1000 ng/mL (Ribociclib ), and 10–600 ng/mL (Letrozole ) with correlation coefficients meeting ICH M10 acceptance criteria. Accuracy, precision, recovery, and selectivity were within acceptable limits. Stability studies in plasma and stock solutions confirmed analyte stability under all tested conditions, with negligible degradation observed. The optimized method demonstrated a short chromatographic runtime and simple sample preparation, enabling rapid analysis of multiple samples.

Conclusion:
The validated HPLC-UV method is simple, precise, and robust. It offers the first reported simultaneous quantification of Palbociclib, Ribociclib and Letrozole in human plasma and is suitable for pharmacokinetic studies, bioequivalence testing, and therapeutic drug monitoring in clinical trails

Phototoxic reactions are of particular concern for pharmaceuticals, cosmetics, and other consumer products that absorb UV-visible light, as they can result in skin damage and increased cancer risk. Current in vitro strategies, such as the 3T3 Neutral Red Uptake and reconstructed human epidermis assays, mainly address photocytotoxicity but fail to capture light-induced DNA damage (photogenotoxicity), a key endpoint for long-term health effects. To overcome these limitations, we developed an in vitro alkaline comet assay in HaCaT human keratinocytes, focusing on biomarkers of light-induced DNA damage (photogenotoxicity). Cytotoxicity was monitored through MTT and LDH assays, while DNA strand breaks served as a biomarker of genotoxic stress. Six reference chemicals (sodium dodecyl sulfate, chlorpromazine, benzophenone-3, 8-methoxypsoralen -8-MOP-, p-phenylenediamine, and 6-methylcoumarin – 6-MC-) were tested. Following UV-A irradiation (4 J/cm²), photocytotoxicity was quantified using Photo-Irritation Factor (PIF) and Mean Photo Effect (MPE) values, while genotoxic effects were determined by the comet assay at immediate and 24 h post-exposure. Phototoxicity was evident for benzophenone-3, 8-MOP, 6-MC and chlorpromazine, reflected in elevated PIF/MPE values. DNA damage, as detected by comet assay, was significant for benzophenone-3, p-phenylenediamine, and chlorpromazine, but absent for 8-MOP, consistent with its DNA crosslinking properties. Importantly, no persistence of DNA strand breaks was observed after 24 h, indicating DNA repair biomarkers of recovery. Altogether, cytotoxicity and genotoxicity biomarkers identified in this study highlight the alkaline comet assay as a relevant tool to detect photogenotoxic hazards in vitro.

Acknowledgement: Proyecto PID2020-113186RB-I00 fund by MCIN/AEI/10.13039/501100011033

Background: This study aimed to investigate the in vitro antibacterial, antifungal, anticandidal, and anticancer effects of 3-hydrazinoquinoxaline-2-thiol, as well as its in silico properties. The compound's effectiveness was evaluated against various bacterial strains, fungal species, Candida species, and its potential anticancer effects.

Method: In vitro assays were conducted to evaluate the antibacterial, antifungal, anticandida, and anticancer activities of 3-hydrazinoquinoxaline-2-thiol. Antibacterial activity was tested against both Gram-positive and Gram-negative bacteria, while antifungal and anticandida effects were assessed on various fungal and Candida species. Anticancer activity was evaluated using the MTT assay on multiple cancer cell lines, including breast, colorectal, leukemia, and glioblastoma cell lines. Migration and colony formation assays were also performed. In silico studies investigated the compound's mode of action, safety, and pharmacokinetic properties.

Result: The compound 3-hydrazinoquinoxaline-2-thiol exhibited significant antibacterial activity. Against E. coli, Klebsiella pneumoniae, and Staphylococcus aureus, the compound showed mean inhibition zones of 18.33 ± 1.25 mm, 10.5 ± 4.27 mm, and 13.83 ± 4.41 mm, respectively. For filamentous fungi (Alternaria sp., Sclerotinia sclerotiorum, Fusarium equiseti), the compound effectively reduced growth, with mean values of 1.81 ± 0.05, 2.29 ± 0.04, and 2.40 ± 0.10, respectively. Regarding Candida species, C. albicans, C. dubliniensis, and C. parapsilosis demonstrated inhibition with mean values of 1.93 ± 0.29, 1.68 ± 0.22, and 0.85 ± 0.17, respectively. Preliminary anticancer results from the MTT assay indicate potential activity against various cancer cell lines.

Conclusion: 3-Hydrazinoquinoxaline-2-thiol demonstrates potent in vitro antibacterial, antifungal, and anticandidal properties, along with promising anticancer potential. In silico studies further support its therapeutic potential, warranting further exploration for clinical