Sangkil Lee

Purpose: This study aimed to develop a polyvinylpyrrolidone (PVP)-based amorphous solid dispersion (ASD) formulation to prevent the crystallization of tegoprazan (TPZ) during long-term storage and to establish a foundation for commercial tablet manufacturing. Methods: The solubility of TPZ-ASD was evaluated in water and buffer solutions. Flowability was assessed using Carr’s Index and the Hausner ratio (HR), and the results were compared with those of amorphous TPZ (TPZ-Am) and crystalline TPZ (TPZ-Cr). Recrystallization during storage was monitored using differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) under both long-term (25 ℃, 60% relative humidity [RH]) and accelerated (40 ℃, 75% RH) conditions. The dissolution profiles of tablets prepared with TPZ-ASD were compared with those of a commercial product. Results: TPZ-ASD exhibited approximately a 20-fold increase in water solubility compared to TPZ-Cr and showed enhanced solubility across all tested pH conditions. Carr’s Index and HR value indicated that TPZ-ASD had better flowability than both TPZ-Cr and TPZ-Am. Stability analyses using DSC and PXRD revealed no recrystallization for up to 24 months (raw material) and 12 months (tablet) under long-term storage conditions and for 6 months under accelerated conditions, respectively. A human pharmacokinetic study demonstrated that the TPZ-ASD tablet was bioequivalent to the commercial product. Conclusion: The PVP-based solid dispersion effectively inhibited TPZ crystallization over an extended period. Furthermore, the TPZ-ASD formulation proved successfully applicable to the manufacturing process, and the commercial potential of this technology was identified in a Phase 1 clinical pharmacokinetics study.

FYN, a member of the Src family kinases (SFKs) and a non-receptor tyrosine kinase, plays a critical role in signal transduction within the nervous system and is instrumental in the activation and development of T lymphocytes. While the biological significance of FYN kinase in various cellular processes is well recognized, its potential as a therapeutic target remains largely unexplored. In this study, we investigated the potential of natural products (NPs) as preferential inhibitors of FYN kinase. A library of over 3500 NPs was screened for binding affinity with FYN kinase (PDB: 2DQ7) using XGlide docking simulations. The fourteen NPs with the highest docking scores were selected for further analysis. Their interactions with FYN kinase were evaluated through MM-GBSA calculations, and ADMET profiling was performed using SwissADME and pkCSM tools to assess pharmacokinetic properties. Molecular dynamics (MD) simulations using Desmond further confirmed the stability of FYN-NP complexes in solvent environments. Of the top fourteen NPs, only oroxin A demonstrated favorable drug-like properties and sustained stable binding to FYN kinase, as evidenced by MD simulations. Moreover, in vitro kinase inhibition assays revealed that oroxin A exhibited dose-dependent inhibition of FYN kinase. Additionally, C. elegans viability assays confirmed its low toxicity. Moreover, cross-docking revealed that although oroxin A binds to multiple SFKs due to conserved ATP binding pocket, it displayed stronger binding toward FYN, suggesting binding preference over FYN. This study provides a comprehensive evaluation of NPs as potential FYN kinase inhibitors and identifies oroxin A as a natural compound with preliminary evidence of FYN inhibition, warranting further validation.

Human bone morphogenetic protein 2 (BMP2) is a key inducer of osteogenesis; however, conventional delivery systems often result in burst release and adverse effects. To address this limitation, we fabricated an ionic complex of BMP2 with the clinically used osteogenesis inducer risedronate drug through an ion-pairing method. Fourier-transform infrared spectroscopy and ultra-resolution imaging confirmed the electrostatic interactions between BMP2 and risedronate. The resulting BMP2—risedronate complex exhibited a uniform particle size of 326 ± 149 nm, a polydispersity index of 0.2–0.3, and a zeta potential of − 38.08 ± 0.12 mV. The complex demonstrated a high complexation efficiency (˃ 95%). In vitro bioactivity studies using C2C12 myoblast cells demonstrated that BMP2, combined with risedronate, effectively induced osteoblastic differentiation. Furthermore, incorporation of the complex into 1.5% hyaluronic acid (HA) and 1% HA–19% poloxamer 407 (P407) hybrid hydrogel mitigated rapid release and retention, achieving a controlled release profile. In vivo studies confirmed that fabricated BMP2—risedronate complex loaded in hydrogels promotes sustained BMP2 release and, in combination with risedronate, enhances osteogenic efficacy. These findings suggest that the BMP2–risedronate ionic complex is a promising candidate for localized BMP2 delivery in osteogenesis therapy.

Background: Lipid-based drug delivery systems are widely used to enhance the bioavailability of various pharmaceutical agents. They offer several advantages, including biocompatibility, biodegradability, and low toxicity. However, they are often limited by formulation leakage, oxidation, hydrolysis, and short half-life. Area covered: This review introduces the components of cochleates, mechanisms underlying their formation and absorption, and diverse preparation methods, along with their advantages and disadvantages. Furthermore, it discusses various analytical techniques for characterizing cochleates formulations and their advantages. A comprehensive review of publications on cochleates from the last decade is provided. Expert opinion: Cochleates have the potential to overcome the inherent limitations of lipid-based drug delivery systems, such as susceptibility to oxidation and degradation by digestive enzymes. They offer several advantageous properties, such as enhanced cellular uptake and permeation, improved bioavailability, and low toxicity. In particular, the potential for oral administration and cancer-targeted accumulation make cochleates promising for drug delivery applications. Despite these advantages, challenges like difficulties in optimizing its composition, physical aggregation, and high costs must be addressed. Also, the lack of approved drugs based on this technology is a major limitation.

Neurological disorders, encompassing conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and amyotrophic lateral sclerosis (ALS), pose a significant global health challenge, affecting millions worldwide. With an aging population and increased life expectancy, the prevalence of these disorders is escalating rapidly, leading to substantial economic burdens exceeding trillions of dollars annually. Animal models play a crucial role in understanding the underlying mechanisms of these disorders and developing effective treatments. Various species, including rodents, non-human primates, and fruit flies, are utilized to replicate specific aspects of human neurological conditions. However, selecting the ideal animal model requires careful consideration of its proximity to human disease conditions and its ability to mimic disease pathobiology and pharmacological responses. An Animal Model Quality Assessment (AMQA) tool has been developed to facilitate this selection process, focusing on assessing models based on their similarity to human conditions and disease pathobiology. Therefore, integrating intrinsic and extrinsic factors linked to the disease into the study's objectives aids in constructing a biological information matrix for comparing disease progression between the animal model and human disease. Ultimately, selecting an ideal animal disease model depends on its predictive, face, and construct validity, ensuring relevance and reliability in translational research efforts.