National Institutes of Health, Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, Bethesda, MD, USA.
Fischell Department of Bioengineering, University of Maryland, College Park, MD, USA.
Sci Rep. 2024 Jun 10;14(1):13352. doi: 10.1038/s41598-024-64189-z.
Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.
肝癌是全球第五大癌症相关死亡原因。与静脉注射相比,直接向肿瘤内注射抗癌药物可能会提高治疗效果并减轻不良反应。肿瘤内注射存在一些挑战,例如液体药物制剂可能无法保持局部定位,并且体积分布不可预测。因此,药物输送差异很大,高度依赖于技术。本研究开发并表征了一种 X 射线可成像泊洛沙姆 407(POL)药物输送凝胶,实现了实时反馈。利用三种针状设备,将 POL 或对照碘造影剂溶液注入离体牛肝中。利用锥形束计算机断层扫描(CBCT)评估 3D 分布。无论注射速率如何,POL 凝胶的 3D 分布均表现为局部球形形态。此外,根据注射技术,可有意改变凝胶的 3D 共形分布。当将阿霉素(DOX)加载到 POL 并注入时,光学成像上 DOX 的分布与 CBCT 上碘的分布相匹配,表明 DOX 和碘在组织中的定位具有空间一致性。这种制剂的可控性和局部沉积最终可能会减少对操作人员技术的依赖,减少全身副作用,并通过更可预测的标准化输送,提高治疗的可重复性。