POLYMAT, Applied Chemistry Department, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel de Lardizabal 3, 20018 Donostia-San Sebastián, Spain.
School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast, Northern Ireland BT9 7BL, U.K.
ACS Appl Mater Interfaces. 2024 Sep 11;16(36):47124-47136. doi: 10.1021/acsami.4c07669. Epub 2024 Aug 28.
Nanocrystals (NCs) have entirely changed the panorama of hydrophobic drug delivery, showing improved biopharmaceutical performance through multiple administration routes. NCs are potential highly loaded nanovectors due to their pure drug composition, standing out from conventional polymers and lipid nanoparticles that have limited drug-loading capacity. However, research in this area is limited. This study introduces the concept of surface modification of drug NCs through single-layer poly(ethylene glycol) (PEG) polymerization as an innovative strategy to boost targeting efficiency. The postpolymerization analysis revealed size and composition alterations, indicating successful surface engineering of NCs of the model drug curcumin of approximately 200 nm. Interestingly, mucosal tissue penetration analysis showed enhanced entry for fully coated and low cross-linked (LCS) PEG NCs, with an increase of 15 μg/cm compared to the control NCs. In addition, we found that polymer chemistry variations on the NCs' surface notably impacted mucin binding, with those armored with LCS PEG showing the most significant reduction in interaction with this glycoprotein. We validated this strategy in an in vitro nose-to-brain model, with all of the NCs exhibiting a promising ability to cross a tight monolayer. Furthermore, the metabolic and pro-inflammatory activity revealed clear indications that, despite surface modifications, the efficacy of curcumin remains unaffected. These findings highlight the potential of surface PEGylated NCs in targeted drug delivery. Altogether, this work sets the baseline for further exploration and optimization of surface polymerized NCs for enhanced drug delivery applications, promising more efficient treatments for specific disorders and conditions requiring active targeting.
纳米晶体（NCs）彻底改变了疏水性药物传递的格局，通过多种给药途径显示出改善的生物制药性能。NCs 是潜在的高载药纳米载体，因为它们的药物组成纯净，与药物载量有限的传统聚合物和脂质纳米粒不同。然而，该领域的研究有限。本研究通过单层聚乙二醇（PEG）聚合介绍了药物 NCs 表面修饰的概念，这是一种提高靶向效率的创新策略。聚合后分析显示大小和组成发生了变化，表明模型药物姜黄素的 NCs 表面工程成功，其粒径约为 200nm。有趣的是，黏膜组织穿透分析显示，完全包被和低交联（LCS）PEG NCs 的进入能力增强，与对照 NCs 相比增加了 15μg/cm。此外，我们发现 NCs 表面聚合物化学变化显著影响粘蛋白结合，其中用 LCS PEG 武装的 NCs 与这种糖蛋白的相互作用减少最为显著。我们在体外鼻脑模型中验证了这一策略，所有 NCs 都表现出穿过紧密单层的有希望的能力。此外，代谢和促炎活性清楚地表明，尽管进行了表面修饰，但姜黄素的疗效不受影响。这些发现突显了表面 PEG 化 NCs 在靶向药物传递中的潜力。总的来说，这项工作为进一步探索和优化用于增强药物递送应用的表面聚合 NCs 奠定了基础，有望为需要主动靶向的特定疾病和病症提供更有效的治疗方法。
