Treatment of metastatic lymph nodes (LNs) is challenging due to their unique architecture and biophysical traits. Systemic chemotherapy fails to impede tumor progression in LNs due to poor drug uptake and retention by LNs, resulting in fatal systemic metastasis. To effectively treat LN metastasis, achieving specific and prolonged retention of chemotherapy drugs in the tumor-draining LNs is essential. The lymphatic drug-delivery system (LDDS) is an ultrasound-guided drug-delivery methodology for administration of drugs to LNs that addresses these requirements. However, early-stage metastatic LNs have an additional set of drug transport barriers, such as elevated intranodal pressure and viscosity, that negatively impact drug diffusion. In the present study, using formulations of elevated osmotic pressure and viscosity relative to saline, we sought to favorably alter the LN's physical environment and study its impact on pharmacokinetics and consequently the therapeutic efficacy of carboplatin delivered using the LDDS. Our study confirmed the capability of a drug formulation with elevated osmotic pressure and viscosity to alter the architecture of LNs, as it caused notable expansion of the lymphatic sinus. Additionally, the study delineated an optimal range of osmotic pressure and viscosity, centered around 1897 kPa and 11.5 mPa·s, above and below which therapeutic efficacy was found to decline markedly. These findings suggest that formulation osmotic pressure and viscosity are parameters that require critical consideration as they can both hinder and promote tumorigenesis. The facile formulation reported here has wide-ranging applicability across cancer spectrums and is thus anticipated to be of great clinical benefit.

中文翻译：

---

药物制剂增强了通过淋巴药物递送系统给药的卡铂的治疗反应

由于其独特的结构和生物物理特性，转移性淋巴结 (LN) 的治疗具有挑战性。由于 LN 的药物摄取和保留不良，全身化疗无法阻止 LN 中的肿瘤进展，从而导致致命的全身转移。为了有效治疗 LN 转移，实现化疗药物在肿瘤引流 LN 中的特异性和长期保留至关重要。淋巴药物输送系统 (LDDS) 是一种超声引导的药物输送方法，用于向淋巴结给药以满足这些要求。然而，早期转移性 LNs 有一组额外的药物传输障碍，例如升高的结内压力和粘度，这会对药物扩散产生负面影响。在本研究中，使用相对于盐水提高渗透压和粘度的制剂，我们试图有利地改变 LN 的物理环境，并研究其对药代动力学的影响，从而研究使用 LDDS 递送的卡铂的治疗效果。我们的研究证实了渗透压和粘度升高的药物制剂能够改变 LN 的结构，因为它会导致淋巴窦显着扩张。此外，该研究描绘了渗透压和粘度的最佳范围，以 1897 kPa 和 11.5 mPa·s 为中心，高于和低于该范围治疗效果会显着下降。这些发现表明，制剂渗透压和粘度是需要认真考虑的参数，因为它们既可以阻碍也可以促进肿瘤发生。