Scientia Pharmaceutica

Chronic and difficult-to-heal wounds require topical agents that combine reparative activity with favorable local disposition and an acceptable preliminary safety profile. This study evaluated three orotic acid–1,2,4-triazole hybrids (1–3) using an integrated computational and experimental workflow. Accelerated weight histogram simulations were performed in an atomistic human stratum corneum lipid model; acute toxicity was assessed by in silico rat LD₅₀ prediction, 96 h Danio rerio LC₅₀ testing, and OECD 425 oral testing in rats. Compounds selected on the basis of toxicity were incorporated into electrospun polyvinylpyrrolidone K-30 dressings and evaluated in a rat excisional wound model. Compound 1 showed pronounced lipid partitioning and potential intralamellar retention, whereas compounds 2 and 3 encountered broad membrane-interior free-energy barriers. Compound 2 had the least favorable acute-toxicity profile and was excluded. By day 8, wound area decreased by 89.0% with compound 1 and 78.6% with compound 3, versus 70.5% with the drug-free vehicle dressing (p < 0.001 for both comparisons). Neither treatment caused clinically evident deterioration or a consistent biochemical pattern of marked hepatic or renal dysfunction, although hematological and compound-specific biochemical changes were observed. The compound 1-loaded dressing therefore warrants further mechanistic, histological, and longer-term safety evaluation as the lead formulation.

Beta-amyloid peptide (Aβ), the key pathogenic factor of Alzheimer’s disease (AD), induces oxidative stress-mediated neuronal damage, eventually leading to death. Madecassic acid (MAD), a natural triterpenoid isolated from Centella asiatica, has been reported for many biological activities, including neuroprotective effects. The low solubility and poor bioavailability of MAD are major limitations; hence, the present study focused on formulating MAD in a nanostructured lipid carrier (NLC-MAD) and evaluating its protective effect against oxidative stress induced by Aβ (25–35) in Neuro-2A cells. NLC-MAD, made of 7.5% total lipid, 50% liquid oil, and 6% surfactant with desirable qualities, was selected for further studies. NLC-MAD exhibited potent free radical scavenging activity (IC₅₀ value 80.20 ± 0.05 μg/mL), reducing power, total antioxidant power, and metal chelating activity (IC₅₀ value 120.12 ± 0.02 µg/mL). NLC-MAD showed a dose-dependent inhibition of acetyl and butyrylcholinesterase with IC₅₀ values of 12.5 ± 0.001 and 30 ± 0.02 µg/mL, respectively. NLC-MAD attenuated Aβ peptide aggregation and disaggregated the preformed mature fibrils. NLC-MAD pretreated Neuro-2A cells attenuated Aβ-induced toxicity dose-dependently and attenuated oxidative stress-mediated toxicity. Safety evaluation studies revealed that NLC-MAD is neither cytotoxic nor hemolytic under in vitro conditions and exhibited no adverse effects under in vivo conditions, indicating a non-toxic nature. The results warrant further studies on the stability of NLC-MAD and preclinical studies before consideration to clinical trials.

Bisoprolol and Lisinopril are among the most frequently used substances in pediatric cardiovascular affections. The medication supply to this age population is limited given the lack of appropriate pharmaceutical forms; therefore, pharmaceutical compounding comes to fill in the gap between pediatric therapy needs and availability of adult-approved formulations. The aim of our study was to obtain and quantify two suspensions of Bisoprolol and Lisinopril in small pediatric dosage. The suspensions were obtained using a commercial suspending vehicle and the active substances. We developed the quality control methods according to the USP. Briefly, both methods were developed and validated using a UHPLC Flexar 10 system (Perkin Elmer) equipped with a Phenomenex Luna C8 column (150 × 4.6 mm, 3 μm) under isocratic conditions at a flow rate of 1 mL/min. For bisoprolol, the mobile phase consisted of water (65:35, v/v) with the specified additives, with detection at 273 nm, while lisinopril was analyzed using 10 mM ammonium formate buffer (pH 5) (96:4, v/v), with detection at 210 nm. The calibration ranges were 30–90 μg/mL for bisoprolol and 20–100 μg/mL for lisinopril. We obtained satisfactory results for method validation, and the method was applied for the assay of two types of suspensions. The obtained results ranged between 80 and 86% of the labeled amounts for Bisoprolol, and 106–108% for Lisinopril. The obtained suspensions reflected some issues related to the sample extraction and potential variability in suspension sampling and dosing consistency, which support the need for continuous optimization and quality control of compounded pediatric formulation.