Scholarlink

<p>Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to late diagnosis, stromal barriers, and therapeutic resistance. Glycyrrhizin (GL), a bioactive compound with anticancer and anti-inflammatory properties, holds promise but suffers solubility and bioavailability limitations. This study develops GL-loaded nanomicelles (GL-NMs) to enhance drug delivery and therapeutic efficacy against PDAC. GL-NMs were synthesized using Pluronic F-127, chitosan, and polyvinyl alcohol. Molecular docking assessed GL’s interactions with key proteins:PDB ID (FAK:6YR9 (HFF cells), MRP5:8WI0 (Panc-1, MIA PaCa-2), PFKFB3:5AJV (A375)) implicated in cancer progression. Physicochemical characterization included dynamic light scattering (DLS), Fourier transform infrared (FTIR), and field emission scanning electron (FESEM). In vitro evaluations encompassed cytotoxicity (MTT assay), apoptosis (DAPI staining, qPCR), and antimicrobial activity (disk diffusion, MIC/MBC). GL exhibited strong binding affinity to PFKFB3 (<i>S</i>-score =  − 10.92) and MRP5 (<i>S</i>-score =  − 10.26), suggesting therapeutic potential. GL-NMs demonstrated monodisperse morphology (258.7 ± 4.2&#xa0;nm hydrodynamic diameter, PDI 0.27), high encapsulation efficiency (87.4 ± 2.1%), and sustained drug release (85.3 ± 2.5% at 120&#xa0;h). Selective cytotoxicity was observed in pancreatic (IC<sub>50</sub> = 238 ± 8&#xa0;µg/mL) and melanoma (IC<sub>50</sub> = 246 ± 9&#xa0;µg/mL) cells, with minimal harm to normal fibroblasts. Apoptosis involved BAX upregulation (2.8-fold), BCL-2 suppression (3.2-fold), and caspase-8 activation (1.9-fold). GL-NMs also showed enhanced antibacterial activity (e.g., <i>E. coli</i> MIC = 75&#xa0;µg/mL vs. 125&#xa0;µg/mL for free GL). GL-NMs synergize GL’s bioactivity with nanomicellar advantages, offering dual anticancer and antimicrobial functionality. The platform’s colloidal stability, tumor selectivity, and controlled release address critical limitations of conventional therapies. This study underscores the potential of GL-NMs as a multifunctional strategy for PDAC treatment, warranting further preclinical validation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Evaluation of Effectiveness Chitosan-Pluronic Nanocarriers Enhance Glycyrrhizin Delivery for Pancreatic Ductal Adenocarcinoma Therapy and Antimicrobial Synergy: An In Silico and In Vitro Study

  • 期刊论文

  • 发表日期：

    2025年8月12日

查看全文
  • Ahmed Hassan Hasnawi Al-Zubaidi,
  • Mohammad Taghi Goodarzi,
  • Elnaz Haghighi,
  • Mohsen Masoumian Hosseini,
  • Niloufar Khatamian,
  • Zahra Namazibaygi,
  • Masoud Homayouni Tabrizi

摘要

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy due to late diagnosis, stromal barriers, and therapeutic resistance. Glycyrrhizin (GL), a bioactive compound with anticancer and anti-inflammatory properties, holds promise but suffers solubility and bioavailability limitations. This study develops GL-loaded nanomicelles (GL-NMs) to enhance drug delivery and therapeutic efficacy against PDAC. GL-NMs were synthesized using Pluronic F-127, chitosan, and polyvinyl alcohol. Molecular docking assessed GL’s interactions with key proteins:PDB ID (FAK:6YR9 (HFF cells), MRP5:8WI0 (Panc-1, MIA PaCa-2), PFKFB3:5AJV (A375)) implicated in cancer progression. Physicochemical characterization included dynamic light scattering (DLS), Fourier transform infrared (FTIR), and field emission scanning electron (FESEM). In vitro evaluations encompassed cytotoxicity (MTT assay), apoptosis (DAPI staining, qPCR), and antimicrobial activity (disk diffusion, MIC/MBC). GL exhibited strong binding affinity to PFKFB3 (S-score =  − 10.92) and MRP5 (S-score =  − 10.26), suggesting therapeutic potential. GL-NMs demonstrated monodisperse morphology (258.7 ± 4.2 nm hydrodynamic diameter, PDI 0.27), high encapsulation efficiency (87.4 ± 2.1%), and sustained drug release (85.3 ± 2.5% at 120 h). Selective cytotoxicity was observed in pancreatic (IC50 = 238 ± 8 µg/mL) and melanoma (IC50 = 246 ± 9 µg/mL) cells, with minimal harm to normal fibroblasts. Apoptosis involved BAX upregulation (2.8-fold), BCL-2 suppression (3.2-fold), and caspase-8 activation (1.9-fold). GL-NMs also showed enhanced antibacterial activity (e.g., E. coli MIC = 75 µg/mL vs. 125 µg/mL for free GL). GL-NMs synergize GL’s bioactivity with nanomicellar advantages, offering dual anticancer and antimicrobial functionality. The platform’s colloidal stability, tumor selectivity, and controlled release address critical limitations of conventional therapies. This study underscores the potential of GL-NMs as a multifunctional strategy for PDAC treatment, warranting further preclinical validation.