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Purpose The established two-analyte integrated population pharmacokinetic model was applied to assess the impact of intrinsic/extrinsic factors on the pharmacokinetics (PK) of polatuzumab vedotin (pola) in patients with non-Hodgkin lymphoma (NHL) following bodyweight-based dosing. Methods Model simulations based on individual empirical Bayes estimates were used to evaluate the impact of intrinsic/extrinsic factors as patient subgroups on Cycle 6 exposures. Intrinsic factors included bodyweight, age, sex, hepatic and renal functions. Extrinsic factors included rituximab/obinutuzumab or bendamustine combination with pola and manufacturing process. The predicted impact on exposures along with the established exposure-response relationships were used to assess clinical relevance. Results No clinically meaningful differences in Cycle 6 pola exposures were found for the following subgroups: bodyweight 100–146 kg versus 38–versus versus male, mild hepatic impairment versus normal, mild-to-moderate renal impairment versus normal. Co-administration of rituximab/obinutuzumab or bendamustine, and change in the pola manufacturing process, also had no meaningful impact on PK. Conclusions In patients with NHL, bodyweight-based dosing is adequate, and no further dose adjustment is recommended for the heavier subgroup (100–146 kg). In addition, no dose adjustments are recommended for other subgroups based on intrinsic/extrinsic factors evaluated.

The focus of this research was to formulate and evaluate a theranostic liposomal delivery system using indocyanine green (ICG) as a photosensitizer, triggered by near infrared (NIR) irradiation, for in vivo photodynamic therapy (PDT) of breast cancer.Cytotoxicity of PDT using liposomal ICG (LPICG) as well as free ICG (FRICG) was evaluated in the human MDA-MB-468 triple-negative breast cancer (TNBC) cell line. NIR irradiation-induced increase in temperature was also monitored both in vitro and in vivo. Quantitative pharmacokinetic profile and fluorescence imaging-based biodistribution patterns of both formulations were obtained using the human TNBC xenograft model in nude mice. Overall safety, tolerability, and long-term anti-tumor efficacy of LPICG versus FRICG-mediated PDT was evaluated.Significant loss of cell viability was achieved following photoactivation of LPICG via NIR irradiation. Temperatures of irradiated LPICG increased with increasing concentrations of loaded ICG, which correlated with significant rise of temperature compared to PBS in vivo (p 0.01). Pharmacokinetic assessment revealed a significant increase in systemic distribution and circulation half-life of LPICG, and NIR fluorescence imaging demonstrated enhanced accumulation of liposomes within the tumor region. Tumor growth in mice treated with LPICG followed by NIR irradiation was significantly reduced compared to those treated with FRICG, saline, and irradiation alone.In vivo photodynamic therapy using LPICG demonstrated targeted biodistribution and superior anti-tumor efficacy in a human TNBC xenograft model compared to FRICG. In addition, this unique delivery system exhibited a promising role in NIR image-guided delivery and real-time biodistribution monitoring of formulation with ICG serving as the fluorescent probe.

To engineer optimized near-infrared (NIR) active thermosensitive liposomes to potentially achieve image-guided delivery of chemotherapeutic agents.Thermosensitive liposomes were surface-coated with either polyethylene glycol or dextran. Differential scanning calorimetry and calcein release studies were conducted to optimize liposomal release, and flow cytometry was employed to determine the in vitro macrophage uptake of liposomes. Indocyanine green (ICG) was encapsulated as the NIR dye to evaluate the in vivo biodistribution in tumor-bearing mice.The optimized thermosensitive liposome formulation consists of DPPC, SoyPC, and cholesterol in the 100:50:30 molar ratio. Liposomes with dextran and polyethylene glycol demonstrated similar thermal release properties; however in vitro macrophage uptake was greater with dextran. Non-invasive in vivo NIR imaging showed tumor accumulation of liposomes with both coatings, and ex vivo NIR imaging correlated well with actual ICG concentrations in various organs of healthy mice.The optimized thermosensitive liposome formulation demonstrated stability at 37 °C and efficient burst release at 40 and 42 °C. Dextran exhibited potential for application as a surface coating in thermosensitive liposome formulations. In vivo studies suggest that liposomal encapsulation of ICG permits reliable, real-time monitoring of liposome biodistribution through non-invasive NIR imaging.