Background: Nanocarriers for antibacterial drugs became hopeful tools against the increasing resistance of bacteria to antibiotics. This work focuses on a comprehensive study of the applicability and therapeutic suitability of dermal carbopol-based hydrogels containing chloramphenicol carried by various nanoparticles (AuNPs and SiNPs). Methods: The different forms of carbopol-based drugs for dermal use were obtained. Five different concentrations of chloramphenicol and two types of nanoparticles (silica and gold) in carbopol-based ointments were tested. The influence of different carbopol formulations with nanocarriers on the rheological properties as well as the release profile of active substances and bacteriostatic activity on five reference strains were determined. Results: The properties of the obtained hydrogels were compared to a commercial formulation, and finally it was possible to obtain a formulation that allowed improved antimicrobial activity over a commercially available detreomycin ointment while reducing the concentration of the antibiotic. Conclusion: The work indicates that it is possible to reduce the concentration of chloramphenicol by four times while maintaining its bacteriostatic activity, which can improve the patient’s safety profile while increasing the effectiveness of the therapy. Graphical

Background: Lidocaine, classified as an amide-type agent, and tetracaine, designated as an ester-type agent, are frequently co-formulated for dermatologic procedures. Despite the extensive literature on the pharmacokinetics (PK) of these substances, there is a paucity of head-to-head comparisons of intravenous (IV) and topical administration in the same preclinical model. Absolute bioavailability (F%) is imperative for optimizing formulation design and safety. Methods: A single-dose, single-sequence, three-period pilot study was performed in male Göttingen mini-pigs. The first period of the study involved the intravenous bolus administration of lidocaine HCl and tetracaine HCl, with a dosage of 1 mg/kg for each agent. In Period 2, the topical application of Pliaglis (a combination of 7% lidocaine and 7% tetracaine, with a concentration of 10 g/100 cm² and a duration of 60 min) was utilized. In Period 3, the pharmacokinetic profile of Z4T4L4 (a formulation comprising 4% lidocaine HCl and 4% tetracaine HCl) was assessed under the same experimental conditions. Blood samples were collected up to 24 h after the administration of the drug; skin biopsies were obtained 90 min after the application of the test substance. Plasma and skin concentrations were measured by means of validated liquid chromatography–tandem mass spectrometry (LC–MS/MS). PK parameters were derived using a noncompartmental analysis approach, while F% was calculated through AUC comparison with IV dosing. Results: Subsequent to intravenous administration, the mean elimination half-lives of lidocaine and tetracaine were determined to be 1.62 h and 1.85 h, respectively. Pliaglis demonstrated higher skin concentrations of lidocaine (358 μg/g) and tetracaine (465 μg/g) compared to Z4T4L4 (33.6 μg/g and 46.1 μg/g, respectively). Despite lower skin levels, Z4T4L4 produced higher F% (lidocaine: 1.98% vs. 1.41%; tetracaine: 3.34% vs. 1.26%). The time to maximum plasma concentration (T_max) for lidocaine was found to be 2–4 h (Pliaglis) and 2–8 h (Z4T4L4), while for tetracaine, it was 1–8 h (Pliaglis) and 2–8 h (Z4T4L4). Conclusions: In this preliminary study, which included three subjects, Z4T4L4 exhibited a numerical tendency towards increased systemic bioavailability in comparison with Pliaglis. This observation was noted despite the fact that Z4T4L4 resulted in markedly lower skin concentrations. Due to the exploratory nature of the pilot study (n = 3), observed differences are reported as numerical trends. The data suggest that Z4T4L4 may enhance systemic absorption while reducing skin retention, highlighting a potential formulation-dependent dissociation between local concentration and systemic bioavailability. These preliminary findings provide in vivo evidence of a divergence between eutectic-based tissue retention and enhancer-driven systemic flux. This highlights that formulation design fundamentally dictates the safety profile of local anesthetics, necessitating a balance between local efficacy and systemic safety.

Given the extended time over which diabetes treatment is administered, the transdermal delivery system is anticipated to be a more suitable option for older individuals who may experience difficulty swallowing. The continuous delivery of dapagliflozin and more stable plasma levels are anticipated to reduce the incidence of side effects and the frequency of dosing. The objectives of the study were to determine the safety and plasma pharmacokinetics of dapagliflozin in male minipigs following application of the ointment and skin patch. In the initial phase of the study, the potential for transdermal permeation of dapagliflozin from ointment and transdermal patch to blood plasma of 15 male Göttingen minipigs was investigated. In the subsequent phase, the efficacy of utilising patches of varying strengths and sizes was assessed. The LC/MS method was employed to quantify the concentration of the active substance. The transportation of the studied API to the general circulation and accumulation in tissues were confirmed. The maximum drug concentration (122.99 ng/mL) in plasma was observed on the fourth day of application. The highest calculated C_max was 131.91 ng/mL with a mean AUC_0-last of 6620.7 ng h/mL. Following transdermal administration, dapagliflozin is excreted in the urine. The trend between urinary dapagliflozin 3-O-glucuronide levels and urinary glucose excretion was also observed. The transdermal patch has been demonstrated to be an effective drug delivery system for dapagliflozin.

Gold nanoparticles have been identified as a promising avenue for the development of drug carriers, particularly in the context of antimicrobial drug delivery, where limited solubility represents a significant challenge. The ability of gold nanoparticles to penetrate biofilms and disrupt fungal cell membranes makes them an effective tool to support antifungal therapy, especially against resistant strains. Gold nanoparticles also demonstrate synergistic effects with chemotherapeutics and can influence the release profile of the active substances. This study aimed to develop a topical hydrogel drug formulation containing itraconazole (ITZ), with the addition of gold nanoparticles, to enhance its therapeutic properties. Due to ITZ’s poor water solubility, three types of the gold nanoparticles (AuNPs) of different sizes were synthesized and subsequently coated with itraconazole. The resulting formulations were incorporated into carbopol gels and their ability to diffuse through semipermeable membranes was assessed. The findings demonstrated that the combination of gold nanoparticles and itraconazole elevated the diffusion coefficient to twice the level observed in gels without nanoparticles. Furthermore, the combined effect of gold nanoparticles and itraconazole against a reference Candida albicans strain was investigated. The combination of gold nanoparticles and itraconazole demonstrated a growth-inhibitory effect on this strain, indicating that this formulation could potentially be employed in the treatment of fungal infections. The study confirms that hydrogels with itraconazole and gold nanoparticles can be obtained, offering enhanced drug diffusion.

Background/Objectives: Burning Mouth Syndrome (BMS) is a common oral condition in older women and is characterized by a multifactorial etiology. To date, no standardized treatment strategy has been established. The aim of this study was to evaluate the effectiveness of topical application of capsaicin (0.025 mg/cm²) in the form of a mucoadhesive bilayer polymer reducing burning sensations in BMS. The study assessed levels of depression, sleep disturbances, and quality of life. Material and Methods: The proof-of-concept study included 29 patients with symptoms of BMS. The peripheral origin of BMS was confirmed by lingual nerve block. Pain intensity was assessed using the Numeric Rating Scale (NRS-11) and the Short-Form McGill Pain Questionnaire (SF-MPQ). Depression, sleep disturbances, and quality of life were evaluated using the Beck Depression Inventory (BDI), Athens Insomnia Scale (AIS), and WHO Quality of Life Questionnaire (WHOQoL). Results: A reduction in pain was observed in over 86% patients. Decrease in burning at treatment sites was recorded immediately after treatment and also at the 3-month follow-up. Gender, taste disturbances, depression, and age were found to have a significant effect on final NRS-11 scores. Conclusions: Significant reduction in pain intensity was achieved in nearly all treated patients, with adverse effects being rare.

Silica nanoparticles were applied as the carrier of chloramphenicol (2,2-dichloro-N-[(1R,2R)-1,3-dihydroxy-1-(4-nitrophenyl)propan-2-yl]acetamide), and were loaded in a 1% carbopol-based gel (poly(acrylic acid)), which allowed obtainment of an upgraded drug form. The samples of silica materials were obtained by means of modified Stöber synthesis, and their morphological properties were analyzed using Fourier transform infrared spectroscopy (FTIR), Brunauer–Emmett–Teller (BET) method, elemental analysis (EA), thermogravimetric analysis (TGA), analysis of the specific surface properties, X-ray diffraction study (XRD), scanning electron microscope (SEM), and dynamic light scattering (DLS) methods, which permitted the selection of the drug carrier. The two obtained silica carriers were coated with chloramphenicol and loaded into 1% carbopol gel. The release studies were then performed. The release results were evaluated using mathematical models as well as model-independent analysis. It was found that the modification of the synthesis of the silica by the sol-gel method to form a product coated with chloramphenicol and further grinding of the silica material influenced the release of the active substance, thus allowing the modification of its pharmaceutical availability. The change in the parameters of silica synthesis influenced the structure and morphological properties of the obtained silica carrier. The grinding process determined the way of adsorption of the active substance on its surface. The studies showed that the proper choice of silica carrier has a considerable effect on the release profile of the prepared hydrogel formulations.