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<p>Intratumoral administration of liposomal chemotherapy improves local specificity in comparison with systemic delivery, but tumor architecture and infusion-induced elevated interstitial fluid pressure limit distribution. This study quantified how infusion strategy, needle design, vascular normalization (VN), and necrotic-core morphology affect fluid transport and pH-sensitive liposomal doxorubicin pharmacokinetics in a subcutaneous breast tumor. A multi-physics finite element framework was developed for a three-layer spherical domain (necrotic core, viable tumor, healthy tissue; radii 5, 10, and 20&#xa0;mm) coupling interstitial flow with microvascular exchange and convection–diffusion-reaction model for nanoliposomes, drug release, binding, metabolism, and cellular internalization. Three infusion architectures delivered 0.1&#xa0;ml of 2&#xa0;mg/ml liposomal doxorubicin: end-hole needle (EHN), five-needle multisite infusion (MSI), and spiral multi-side-hole design (MSH). Pre-infusion simulations showed peak interstitial pressure in the necrotic core (~ 1.53&#xa0;kPa) with velocities significant only near the tumor-healthy interface. Infusion created extreme hypertension (~ 5.8&#xa0;MPa) and strong advection near the outlets. VN reduced the baseline pressure but increased the infusion-site pressure (~ 28.86&#xa0;MPa) with minimal impact on the nanoliposome distribution. Necrotic core size weakly affected infusion pressure, but strongly influenced particle filling, with smaller cores promoting faster saturation. MSI and MSH reduced needle-tip pressure by ~ 70–52% versus EHN and improved viable-tumor delivery; EHN trapped liposomes in the core. Sensitivity analysis confirmed infusion strategy (ή = 1.2) and needle type (ή = 0.95) as the primary pressure determinants. Multi-port/multisite infusion provides a more efficient approach than VN, supporting needle selection based on necrotic core size and lesion geometry.</p>

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Impact of infusion strategies and tumor morphology on the pharmacokinetics of liposomal drug distribution: a quantitative analysis of mass diffusion in intratumoral drug delivery

  • 期刊论文

  • 发表日期：

    2026年5月23日

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  • Aishik Dinda,
  • Sujit Nath

摘要

Intratumoral administration of liposomal chemotherapy improves local specificity in comparison with systemic delivery, but tumor architecture and infusion-induced elevated interstitial fluid pressure limit distribution. This study quantified how infusion strategy, needle design, vascular normalization (VN), and necrotic-core morphology affect fluid transport and pH-sensitive liposomal doxorubicin pharmacokinetics in a subcutaneous breast tumor. A multi-physics finite element framework was developed for a three-layer spherical domain (necrotic core, viable tumor, healthy tissue; radii 5, 10, and 20 mm) coupling interstitial flow with microvascular exchange and convection–diffusion-reaction model for nanoliposomes, drug release, binding, metabolism, and cellular internalization. Three infusion architectures delivered 0.1 ml of 2 mg/ml liposomal doxorubicin: end-hole needle (EHN), five-needle multisite infusion (MSI), and spiral multi-side-hole design (MSH). Pre-infusion simulations showed peak interstitial pressure in the necrotic core (~ 1.53 kPa) with velocities significant only near the tumor-healthy interface. Infusion created extreme hypertension (~ 5.8 MPa) and strong advection near the outlets. VN reduced the baseline pressure but increased the infusion-site pressure (~ 28.86 MPa) with minimal impact on the nanoliposome distribution. Necrotic core size weakly affected infusion pressure, but strongly influenced particle filling, with smaller cores promoting faster saturation. MSI and MSH reduced needle-tip pressure by ~ 70–52% versus EHN and improved viable-tumor delivery; EHN trapped liposomes in the core. Sensitivity analysis confirmed infusion strategy (ή = 1.2) and needle type (ή = 0.95) as the primary pressure determinants. Multi-port/multisite infusion provides a more efficient approach than VN, supporting needle selection based on necrotic core size and lesion geometry.