Bustos Araya Marta E, Ricart Anna Nardi, Calpena Campmany Ana C, Prohens Rafel, Miñarro Carmona Montserrat
Instituto de Investigaciones Farmacéuticas, Facultad de Farmacia, Universidad de Costa Rica, San José 11501, Costa Rica.
Pharmacy, Pharmaceutical Technology and Physico-Chemical Department, University of Barcelona, Av. Joan XXIII, 27-31, 08028 Barcelona, Spain.
Pharmaceutics. 2025 Jan 10;17(1):86. doi: 10.3390/pharmaceutics17010086.
This study explores the development and characterization of lyophilized chondroitin sulfate (CHON)-loaded solid lipid nanoparticles (SLN) as an innovative platform for advanced drug delivery. Solid lipid nanoparticles are increasingly recognized for their biocompatibility, their ability to encapsulate diverse compounds, their capacity to enhance drug stability, their bioavailability, and their therapeutic efficacy. CHON, a naturally occurring glycosaminoglycan with anti-inflammatory and regenerative properties, was integrated into SLN formulations using the hot microemulsion technique. Two formulations (SLN-1 and SLN-2) were produced and optimized by evaluating critical physicochemical properties such as particle size, zeta potential, encapsulation efficiency (EE%), and stability. The lyophilization process, with the addition of various cryoprotectants, revealed trehalose to be the most effective agent in maintaining nanoparticle integrity and functional properties. Morphological analyses using transmission electron microscopy (TEM) and atomic force microscopy (AFM) confirmed the dimensions of the nanoscales and their structural uniformity. Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) revealed minimal excipient interaction with CHON, ensuring formulation stability. Stability studies under different environmental conditions highlighted that SLN-2 is the most stable formulation, maintaining superior encapsulation efficiency (≥88%) and particle size consistency over time. These findings underscore the potential of CHON-loaded SLNs as promising candidates for targeted, sustained-release therapies in the treatment of inflammatory and degenerative diseases.
本研究探索了负载硫酸软骨素（CHON）的冻干固体脂质纳米粒（SLN）的开发与特性，将其作为一种先进药物递送的创新平台。固体脂质纳米粒因其生物相容性、包封多种化合物的能力、增强药物稳定性的能力、生物利用度及治疗效果而日益受到认可。CHON是一种具有抗炎和再生特性的天然存在的糖胺聚糖，采用热微乳技术将其整合到SLN制剂中。通过评估粒径、zeta电位、包封率（EE%）和稳定性等关键物理化学性质，制备并优化了两种制剂（SLN-1和SLN-2）。冻干过程中添加各种冻干保护剂后，发现海藻糖是维持纳米粒完整性和功能特性最有效的试剂。使用透射电子显微镜（TEM）和原子力显微镜（AFM）进行的形态学分析证实了纳米级尺寸及其结构均匀性。差示扫描量热法（DSC）和X射线衍射（XRD）显示辅料与CHON的相互作用最小，确保了制剂的稳定性。不同环境条件下的稳定性研究表明，SLN-2是最稳定的制剂，随着时间推移能保持优异的包封率（≥88%）和粒径一致性。这些发现强调了负载CHON的SLN作为治疗炎症性和退行性疾病的靶向、缓释疗法的有前景候选物的潜力。
