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<p>Ciclopirox (CPX), a hydroxypyridone-class topical antifungal drug, distinct from azole antifungals, has traditionally been used to treat vaginal candidiasis and skin infections. Recently, it has gained attention for repurposing as an anticancer agent due to its ability to inhibit various cancer-associated pathways. This study explores the use of CPX for colorectal cancer (CRC) therapy by formulating it into nanoparticles (NPs) through conjugation with modified citrus pectin (MCP) and chitosan (CHT) using the polyelectrolyte complex method, resulting in a novel CPX-chitosan-pectin (CPX-CHT-PEC)conjugated NPs system. In-silico studies indicated that this conjugated complex effectively targets CRC-related proteins, particularly galectin-3—a key protein implicated in CRC progression. Optimization of formulation parameters such as polymer ratios, crosslinker concentration, stirring speed, and sonication time yielded nanoparticles with an average particle size of 340 ± 10&#xa0;nm, zeta potential of 18 ± 3 mV, polydispersity index (PDI) of 0.72 ± 0.2, and an entrapment efficiency of 72.44 ± 2%. TEM imaging confirmed spherical morphology, while FTIR and NMR analyses validated CPX conjugation. In vitro drug release studies demonstrated a sustained release profile, with 15.30% release at pH 6.4 and 80.91% at pH 7.2, fitting the Korsmeyer–Peppas model. MTT assays on HT-29 cells revealed enhanced cytotoxicity of CPX-conjugated NPs compared to the free drug. In vivo studies using a xenograft model in mice confirmed superior tumor reduction, survival rates, and physiological outcomes with CPX-NPs. These results suggest that CPX-conjugated nanoparticles are a promising, orally deliverable therapeutic system for targeted colorectal cancer treatment.</p>

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Smart Nanocarriers for Colon Cancer: Chitosan–Pectin Mediated Ciclopirox Delivery

  • 期刊论文

  • 发表日期：

    2025年10月20日

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  • Savita Shrikant Deokar,
  • Sangita Abasaheb Kale,
  • Karimunnisa Sameer Shaikh

摘要

Ciclopirox (CPX), a hydroxypyridone-class topical antifungal drug, distinct from azole antifungals, has traditionally been used to treat vaginal candidiasis and skin infections. Recently, it has gained attention for repurposing as an anticancer agent due to its ability to inhibit various cancer-associated pathways. This study explores the use of CPX for colorectal cancer (CRC) therapy by formulating it into nanoparticles (NPs) through conjugation with modified citrus pectin (MCP) and chitosan (CHT) using the polyelectrolyte complex method, resulting in a novel CPX-chitosan-pectin (CPX-CHT-PEC)conjugated NPs system. In-silico studies indicated that this conjugated complex effectively targets CRC-related proteins, particularly galectin-3—a key protein implicated in CRC progression. Optimization of formulation parameters such as polymer ratios, crosslinker concentration, stirring speed, and sonication time yielded nanoparticles with an average particle size of 340 ± 10 nm, zeta potential of 18 ± 3 mV, polydispersity index (PDI) of 0.72 ± 0.2, and an entrapment efficiency of 72.44 ± 2%. TEM imaging confirmed spherical morphology, while FTIR and NMR analyses validated CPX conjugation. In vitro drug release studies demonstrated a sustained release profile, with 15.30% release at pH 6.4 and 80.91% at pH 7.2, fitting the Korsmeyer–Peppas model. MTT assays on HT-29 cells revealed enhanced cytotoxicity of CPX-conjugated NPs compared to the free drug. In vivo studies using a xenograft model in mice confirmed superior tumor reduction, survival rates, and physiological outcomes with CPX-NPs. These results suggest that CPX-conjugated nanoparticles are a promising, orally deliverable therapeutic system for targeted colorectal cancer treatment.