مطالعه عددی اثربخشی درمانی تزریق بولوس و پیوسته بر دارو رسانی به تومور جامد عروقی

نوع مقاله : مقاله پژوهشی

نویسندگان

دانشکده مهندسی مکانیک، دانشگاه صنعتی خواجه نصیرالدین طوسی، تهران، ایران

چکیده

رسانش مؤثر داروها به سلول‌های تومور برای موفقیت اغلب درمان‌های ضد سرطان ضروری است. در این مطالعه، مدلسازی دوبعدی توزیع غلظت فضایی-زمانی دوکسوروبیسین تحت تزریق بولوس و پیوسته ارائه شده است. شبیه‌سازی‌های ریاضی با در نظر گرفتن فرآیندهای فیزیکی و بیوشیمیایی اصلی در دارورسانی به سلول‌های تومور انجام شده است. اثربخشی ضد سرطان از طریق تغییرات در تراکم سلول‌های تومور بر اساس غلظت‌های درون سلولی پیش‌بینی‌شده ارزیابی شد. برخلاف اکثر مدل‌های محاسباتی که توزیع عروق خونی در تومور را یکنواخت فرض کردند، شبکه عروقی با استفاده از یک روش رگزایی جوانه‌زنی تولید می‌شود. نتایج نشان می‌دهد داروها در مناطقی که تراکم عروقی بالاست، بیشتر تجمع می‌کنند و در نتیجه سمیت سلولی دارو بهبود می‌یابد. در مقایسه با تزریق بولوس، تزریق پیوسته منجر به حفظ طولانی‌تر سطح بالای غلظت درون سلولی دارو در تومور می‌شود که در بهبود اثر سمیت موثرتر است. اگرچه تزریق بولوس منجر به 90 درصد پیک غلظت خارج سلولی بالاتر می‌شود، خطر ایجاد عوارض جانبی شدید وجود دارد. همچنین، تزریق پیوسته با نگه‌داشتن دوکسوروبیسین در سطح بالاتر در تومور، منجر به افزایش اثربخشی ضد سرطانی در پایان درمان در حدود 26 درصد نسبت به اثربخشی تزریق بولوس می‌شود.

کلیدواژه‌ها


عنوان مقاله [English]

Numerical Study of Therapeutic Effectiveness of Bolus Injection and Continuous Infusion on Drug Delivery to Vascularized Solid Tumor

نویسندگان [English]

  • Majid Soltani
  • Mohammad Kiani Shahvandi
Department of Mechanical Engineering, K. N. Toosi University of Technology, Tehran, Iran
چکیده [English]

Effective delivery of drugs to tumor cells is essential for the success of most anticancer therapies. In this study, two-dimensional modeling for spatiotemporal distribution of doxorubicin concentration under bolus injection and the continuous infusion is presented. Mathematical simulations have been performed considering the main physical and biochemical processes in drug delivery to tumor cells. Anticancer effectiveness is evaluated through changes in tumor cell density based on predicted intracellular concentrations. Unlike most computational models, which assume a uniform distribution of blood vessels in the tumor, the vascular network is produced using a sprouting angiogenesis method. The results demonstrate that the drugs accumulate more in areas with high vascular density, resulting in improved drug cytotoxicity. Compared to bolus injection, continuous infusion leads to longer high level maintenance of intracellular drug concentrations in the tumor, which is more effective in improving the cytotoxic effect. Although bolus injection leads to a 90% higher extracellular concentration peak, there is the risk of severe side effects. Also, continuous infusion by keeping doxorubicin at a higher level in the tumor leads to improved anticancer effectiveness by about 26% relative to the effectiveness of bolus injection at the end of the treatment.
 

کلیدواژه‌ها [English]

  • Chemotherapy
  • Doxorubicin
  • Drug delivery
  • Solid tumor
  • Vascular network
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