A novel EUS-guided Intratumoral Delivery of Submicron Particle Paclitaxel for the Treatment of Locally Advanced Pancreatic Cancer. A Prospective Safety, Tolerability and Preliminary Efficacy Study.
Background: NanoPac® is patented submicron particle paclitaxel in stable powder form without coating or carrier agents. In a previous PK study, healthy male rats inhaled a single exposure of nebulized NanoPac® (0.37 mg/kg or 1.0 mg/kg) or IV Abraxane® (5.0 mg/kg) with a final necropsy time-point at 14 days. T1/2 of NanoPac® and Abraxane were 56hrs and 20hrs with drug present at 14 days and not after 3 days, respectively. Tissue examined from the last time point were microscopically indistinguishable from non-treated controls.
NanOlogy™, a clinical-stage pharmaceutical development company, was formed in 2015 to increase the effectiveness and safety of CT through targeted delivery. Based on a proprietary submicron particle production technology, the company has developed stable, uncoated submicron particles of the taxanes, paclitaxel and docetaxel, as investigational drugs, which can be administered directly to the site of disease via injection, instillation, or inhalation.
Inhaled chemotherapeutics may enhance pulmonary drug exposure to malignant lesions in the lung without substantially contributing to systemic toxicities. The pharmacokinetic profile of inhaled submicron particle paclitaxel (NanoPac) in healthy rodent plasma and lung tissue is evaluated here to determine administration proof-of-principle.
Suspensions of submicron particle taxanes (Figure 1) allow for direct administration of high, sustained levels of chemotherapeutics at the site of disease. Intratumoral (IT) injections of submicron particles of pure docetaxel (NanoDoce) into clear cell renal carcinoma (786-O), transitional cell bladder carcinoma (UM-UC-3) and prostate carcinoma (PC-3) xenografts were evaluated.