Abstract 2141: IG-001 utilization of albumin mediated transport and its potential application in difficult to perfuse tumors.
Authors: Motamed Kouros , Hwang Larn , Hsiao Chao , Trieu Vuong 
Published: August 2014

Abstract
Study Purpose: nab-paclitaxel (Abraxane), though a breakthrough in paclitaxel formulation, has inherent problems associated with any biologics. IG-001, being a chemical polymer bound nanoparticle paclitaxel instead of biological polymer, is being developed as the next generation nanoparticle paclitaxel. Its target indications are difficult to perfuse hypoxic tumors such as pancreatic cancer, taking advantage of its ability to rapidly deliver paclitaxel to the targeted tissue via albumin mediated transport. Evidence for its ability to utilize albumin-mediated transport as previously described for nab-paclitaxel is presented.
Methods: Stability of IG-001 nanoparticles was evaluated in PBS, plasma, and blood. Tissue pharmacokinetics (PK) and distribution in rodents were also evaluated. Clinical PK of the various formulations were also compared. The pharmacokinetic parameters were estimated by using the noncompartmental open model and the WinNonlin program (Pharsight, CA). Descriptive statistics were computed for PK assessment. Regression analysis of AUCinf vs. dose was performed to gain an appreciation of dose proportionality.
Results: The dissolution profile of IG-001 was similar to that of nab-paclitaxel―being controlled primarily by the solubility limit of paclitaxel. The dissolution profile confirmed that once injected into the circulation, both formulations quickly dissolved into paclitaxel complexed with endogenous circulating albumin. Hence, both formulations appear to be equally capable of utilizing the natural albumin transport system. The PK profiles in rodent and human were similar between the two formulations with large Vss and low AUC/dose relative to the Cremophor-based formulation Taxol. In tumor bearing mice, IG-001 has AUC of 1.54 ug*hr/ml/mg/kg versus Taxol of 4.25 ug*h/ml/mg/kg. Yet tumor AUC of 74.28 ug*h/ml/mg/kg versus 107.00 ug*hr/ml/mg/kg. The ratio of tumor AUC/plasma AUC was 48.2 and 25.2 for IG-001 and Taxol, respectively, with IG-001 having a 1.9 higher tumor penetration than Taxol. In comparison, the ratio of tumor AUC/plasma AUC was 5.1 and 2.6 for nab-paclitaxel and Taxol, respectively, with nab-paclitaxel having a 2.0 higher tumor penetration than Taxol. Nab-paclitaxel and IG-001 exhibit comparable dose proportionality demonstrating the ability to utilize albumin pathway to deliver paclitaxel to tissues unhindered by Cremophor micelles of Taxol. In human, IG-001 exhibited the AUC/dose value of 0.06 uM*h/mg/m2 across the dose levels of 135-390 mg/m2 a dose proportional characteristic of nab-paclitaxel.
Conclusions: A non-albumin-based paclitaxel formulation (IG-001) was found to have similar properties to the albumin-based paclitaxel formulation (nab-paclitaxel). Its clinical development could give us the next generation paclitaxel nanoparticle formulation that can be more readily modified than nab-paclitaxel (Abraxane).
Citation Format: Kouros Motamed, Larn Hwang, Chao Hsiao, Vuong Trieu. IG-001 utilization of albumin mediated transport and its potential application in difficult to perfuse tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2141. doi:10.1158/1538-7445.AM2013-2141