Gupta Ankita, Kushwaha Swatantra K S, Mishra Amit
Dr. APJ Abdul Kalam Technical University, Lucknow, 226031 India.
Department of Pharmaceutics, Bombay College of Pharmacy, Mumbai, 400098 India.
3 Biotech. 2025 Jun;15(6):190. doi: 10.1007/s13205-025-04364-9. Epub 2025 May 27.
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.
本研究聚焦于开发和评估一种创新的壳聚糖接枝二氧化硅纳米载体，其包裹着聚（ADP - 核糖）聚合酶（PARP）抑制剂奥拉帕尼，旨在实现对乳腺癌细胞的靶向递送。该制剂旨在提高癌症治疗的精准度和疗效。通过溶胶 - 凝胶法合成二氧化硅纳米载体（SNs），随后使用γ - 缩水甘油醚氧基丙基三甲氧基硅烷（GPTMS）作为偶联剂，用壳聚糖进行包覆。奥拉帕尼（Ola）成功载入壳聚糖接枝二氧化硅纳米载体（Ola - Ch - SNs）。使用X射线衍射（XRD）、透射电子显微镜（TEM）、动态光散射（DLS）和热重 - 差示扫描量热法（TGA - DSC）等技术对所得纳米载体进行表征。在不同pH条件下于磷酸盐缓冲盐水（PBS）中评估药物释放曲线，同时使用磺酰罗丹明B（SRB）测定法在MCF - 7乳腺癌细胞中测量细胞毒性。成功合成了均匀的、对pH敏感的负载奥拉帕尼的壳聚糖包覆二氧化硅纳米载体（Ola - Ch - SNs），并使用包括扫描电子显微镜（SEM）、透射电子显微镜（TEM）、热重分析（TGA）、差示扫描量热法（DSC）和X射线衍射（XRD）在内的先进技术对其进行表征。纳米载体表现出优异的稳定性，载药效率达到44.31±0.21%，包封率达到83.12±0.08%。观察到明显的pH响应性药物释放行为，在24小时内，pH 4.0时奥拉帕尼的累积释放率达到57.6±0.34%，pH 6.0时达到47.3±0.02%，而在pH 7.4时72小时内为22.6±0.14%。由Korsmeyer - Peppas模型描述的释放动力学表明，其机制是由扩散和聚合物松弛共同驱动的。对MCF - 7乳腺癌细胞进行的体外细胞毒性试验表明，与游离奥拉帕尼相比，Ola - Ch - SNs的抗癌活性增强，在80μg/ml时实现低于10μg/ml的半数生长抑制浓度（GI₅₀）值，并将细胞活力降低至23.4±0.3%。这些发现强调了Ola - Ch - SNs作为一种创新的、靶向药物递送系统用于有效癌症治疗的潜力。我们成功开发了负载奥拉帕尼的pH响应性壳聚糖包覆二氧化硅纳米载体，对乳腺癌细胞显示出显著的细胞毒性。该制剂有望提高奥拉帕尼的生物利用度并推进靶向癌症治疗。
