Dual pH and microbial-sensitive galactosylated polymeric nanocargoes for multi-level targeting to combat ulcerative colitis

IF 10.7 1区 医学 Q1 PHARMACOLOGY & PHARMACY
Mahira Zeeshan , Qurat Ul Ain , Benno Weigmann , Darren Story , Bryan R. Smith , Hussain Ali
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Abstract

Ulcerative colitis (UC) is a type of inflammatory bowel disease characterized by inflammation, ulcers and irritation of the mucosal lining. Oral drug delivery in UC encounters challenges because of multifaceted barriers. Dexamethasone-loaded galactosylated-PLGA/Eudragit S100/pullulan nanocargoes (Dexa-GP/ES/Pu NCs) have been developed with a dual stimuli-sensitive coating responsive to both colonic pH and microbiota, and an underneath galactosylated-PLGA core (GP). The galactose ligand of the GP preferentially binds to the macrophage galactose type-lectin-C (MGL-2) surface receptor. Therefore, both stimuli and ligand-mediated targeting facilitate nanocargoes to deliver Dexa specifically to the colon with enhanced macrophage uptake. Modified emulsion method coupled with a solvent evaporation coating technique was employed to prepare Dexa-GP/ES/Pu NCs. The nanocargoes were tested using in vitro, ex vivo techniques and dextran sodium sulfate (DSS) induced UC model. Prepared nanocargoes had desired physicochemical properties, drug release, cell uptake and cellular viability. Investigations using a DSS-colitis model showed high localization and mitigation of colitis with downregulation of NF-ĸB and COX-2, and restoration of clinical, histopathological, biochemical indices, antioxidant balance, microbial alterations, FTIR spectra, and epithelial junctions’ integrity. Thus, Dexa-GP/ES/Pu NCs found to be biocompatible nanocargoes capable of delivering drugs to the inflamed colon with unique targeting properties for prolonged duration.

Abstract Image

双pH和微生物敏感半乳糖基化聚合物纳米cargo多层次靶向对抗溃疡性结肠炎
溃疡性结肠炎(UC)是一种炎症性肠病,其特征是炎症、溃疡和粘膜衬里刺激。由于多方面的障碍,UC的口服药物递送面临挑战。地塞米松负载的半乳糖基化PLGA/Eudragit S100/普鲁兰纳米货物(Dexa-GP/ES/Pu NCs)已被开发出具有对结肠pH和微生物群都有反应的双重刺激敏感涂层和下层半乳糖基PLGA核心(GP)。GP的半乳糖配体优先结合巨噬细胞半乳糖凝集素-C(MGL-2)表面受体。因此,刺激和配体介导的靶向都有助于纳米货物将Dexa特异性递送到结肠,从而增强巨噬细胞的摄取。采用改进的乳液法结合溶剂蒸发涂布技术制备了Dexa-GP/ES/Pu纳米复合材料。使用体外、离体技术和右旋糖酐硫酸钠(DSS)诱导的UC模型对纳米货物进行了测试。制备的纳米货物具有所需的物理化学性质、药物释放、细胞摄取和细胞活力。使用DSS结肠炎模型进行的研究显示,通过下调NF-ĸB和COX-2,结肠炎得到了高度定位和缓解,并恢复了临床、组织病理学、生化指标、抗氧化平衡、微生物改变、FTIR光谱和上皮连接的完整性。因此,Dexa GP/ES/Pu NCs被发现是一种生物相容性纳米货物,能够以独特的靶向特性将药物长期输送到发炎的结肠。
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来源期刊
Asian Journal of Pharmaceutical Sciences
Asian Journal of Pharmaceutical Sciences Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
18.30
自引率
2.90%
发文量
11
审稿时长
14 days
期刊介绍: The Asian Journal of Pharmaceutical Sciences (AJPS) serves as the official journal of the Asian Federation for Pharmaceutical Sciences (AFPS). Recognized by the Science Citation Index Expanded (SCIE), AJPS offers a platform for the reporting of advancements, production methodologies, technologies, initiatives, and the practical application of scientific knowledge in the field of pharmaceutics. The journal covers a wide range of topics including but not limited to controlled drug release systems, drug targeting, physical pharmacy, pharmacodynamics, pharmacokinetics, pharmacogenomics, biopharmaceutics, drug and prodrug design, pharmaceutical analysis, drug stability, quality control, pharmaceutical engineering, and material sciences.
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