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<p>This study focuses on the development and assessment of innovative chitosan-grafted silica nanocarriers encapsulating the PARP inhibitor, olaparib, designed for targeted delivery in breast cancer cells. The formulation aims to enhance therapeutic precision and efficacy in cancer treatment. Silica nanocarriers (SNs) were synthesized through a sol–gel method and subsequently coated with chitosan, employing GPTMS as a coupling agent. Olaparib (Ola) was successfully incorporated into the chitosan grafted silica nanocarriers (Ola-Ch-SNs). The resulting nanocarriers were characterized using techniques such as XRD, TEM, DLS, and TGA–DSC. Drug release profiles were evaluated in PBS across different pH conditions, while cytotoxicity was measured using the SRB assay in MCF-7 breast cancer cells. Uniform, pH-sensitive olaparib-loaded chitosan-coated silica nanocarriers (Ola-Ch-SNs) were successfully synthesized and characterized using advanced techniques including SEM, TEM, TGA, DSC, and XRD. The nanocarriers demonstrated excellent stability, achieving a drug loading efficiency of 44.31 ± 0.21% and an encapsulation efficiency of 83.12 ± 0.08%. Distinct pH-responsive drug release behavior was observed, with cumulative olaparib release reaching 57.6 ± 0.34% at pH 4.0 and 47.3 ± 0.02% at pH 6.0 over 24&#xa0;h, compared to 22.6 ± 0.14% at pH 7.4 over 72&#xa0;h. Release kinetics, described by the Korsmeyer-Peppas model, indicated a mechanism driven by both diffusion and polymer relaxation. In vitro cytotoxicity assays on MCF-7 breast cancer cells revealed enhanced anticancer activity of Ola-Ch-SNs compared to free olaparib, achieving a GI₅₀ value below 10&#xa0;µg/ml and reducing cell viability to 23.4 ± 0.3% at 80&#xa0;µg/ml. These findings underscore the potential of Ola-Ch-SNs as an innovative, targeted drug delivery system for effective cancer therapy. We successfully developed pH-responsive chitosan-coated silica nanocarriers loaded with olaparib, showcasing remarkable cytotoxicity against breast cancer cells. This formulation holds promise for enhancing olaparib bioavailability and advancing targeted cancer therapies. </p>

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pH-responsive silica nanocarriers of olaparib for augmenting anticancer activity: development, characterization, and in vitro cytotoxicity study against MCF-7 breast cancer cells

  • 期刊论文

  • 发表日期：

    2025年5月27日

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  • Ankita Gupta,
  • Swatantra K. S. Kushwaha,
  • Amit Mishra

摘要

This study focuses on the development and assessment of innovative chitosan-grafted silica nanocarriers encapsulating the PARP inhibitor, olaparib, designed for targeted delivery in breast cancer cells. The formulation aims to enhance therapeutic precision and efficacy in cancer treatment. Silica nanocarriers (SNs) were synthesized through a sol–gel method and subsequently coated with chitosan, employing GPTMS as a coupling agent. Olaparib (Ola) was successfully incorporated into the chitosan grafted silica nanocarriers (Ola-Ch-SNs). The resulting nanocarriers were characterized using techniques such as XRD, TEM, DLS, and TGA–DSC. Drug release profiles were evaluated in PBS across different pH conditions, while cytotoxicity was measured using the SRB assay in MCF-7 breast cancer cells. Uniform, pH-sensitive olaparib-loaded chitosan-coated silica nanocarriers (Ola-Ch-SNs) were successfully synthesized and characterized using advanced techniques including SEM, TEM, TGA, DSC, and XRD. The nanocarriers demonstrated excellent stability, achieving a drug loading efficiency of 44.31 ± 0.21% and an encapsulation efficiency of 83.12 ± 0.08%. Distinct pH-responsive drug release behavior was observed, with cumulative olaparib release reaching 57.6 ± 0.34% at pH 4.0 and 47.3 ± 0.02% at pH 6.0 over 24 h, compared to 22.6 ± 0.14% at pH 7.4 over 72 h. Release kinetics, described by the Korsmeyer-Peppas model, indicated a mechanism driven by both diffusion and polymer relaxation. In vitro cytotoxicity assays on MCF-7 breast cancer cells revealed enhanced anticancer activity of Ola-Ch-SNs compared to free olaparib, achieving a GI₅₀ value below 10 µg/ml and reducing cell viability to 23.4 ± 0.3% at 80 µg/ml. These findings underscore the potential of Ola-Ch-SNs as an innovative, targeted drug delivery system for effective cancer therapy. We successfully developed pH-responsive chitosan-coated silica nanocarriers loaded with olaparib, showcasing remarkable cytotoxicity against breast cancer cells. This formulation holds promise for enhancing olaparib bioavailability and advancing targeted cancer therapies.