INTRODUCTION: An increasing research interest has been directed toward nanoparticle-based drug delivery systems for their advantages. The appropriate amalgamation of pH sensitivity and tumor targeting is a promising strategy to fabricate drug delivery systems with high efficiency, high selectivity and low toxicity. MATERIALS AND METHODS: A novel pH sensitive Cremophor-free paclitaxel formulation, Nanoxel(TM), was developed in which the drug is delivered as nanomicelles using a polymeric carrier that specifically targets tumors. The efficiency and mechanism of intracellular paclitaxel delivery by Nanoxel(TM) was compared with two other commercially available paclitaxel formulations: Abraxane(TM) and Intaxel(TM), using different cell lines representing target cancers [breast, ovary and non-small cell lung carcinoma (NSCLC)] by transmission electron microscopy and quantitative intracellular paclitaxel measurements by high performance liquid chromatography. RESULTS: The data obtained from the present study revealed that the uptake of nanoparticle-based formulations Nanoxel(TM) and Abraxane(TM) is mediated by the process of endocytosis and the uptake of paclitaxel was remarkably superior to Intaxel(TM) in all cell lines tested. Moreover, the intracellular uptake of paclitaxel in Nanoxel(TM)- and Abraxane(TM)-treated groups was comparable. Hence, the nanoparticle-based formulations of paclitaxel (Nanoxel(TM) and Abraxane(TM)) are endowed with higher efficiency to deliver the drug to target cells as compared to the conventional Cremophor-based formulation. CONCLUSION: Nanoxel(TM) appears to be of great promise in tumor targeting and may provide an advantage for paclitaxel delivery into cancer cells.
INTRODUCTION: An increasing research interest has been directed toward nanoparticle-based drug delivery systems for their advantages. The appropriate amalgamation of pH sensitivity and tumor targeting is a promising strategy to fabricate drug delivery systems with high efficiency, high selectivity and low toxicity. MATERIALS AND METHODS: A novel pH sensitive Cremophor-free paclitaxel formulation, Nanoxel(TM), was developed in which the drug is delivered as nanomicelles using a polymeric carrier that specifically targets tumors. The efficiency and mechanism of intracellular paclitaxel delivery by Nanoxel(TM) was compared with two other commercially available paclitaxel formulations: Abraxane(TM) and Intaxel(TM), using different cell lines representing target cancers [breast, ovary and non-small cell lung carcinoma (NSCLC)] by transmission electron microscopy and quantitative intracellular paclitaxel measurements by high performance liquid chromatography. RESULTS: The data obtained from the present study revealed that the uptake of nanoparticle-based formulations Nanoxel(TM) and Abraxane(TM) is mediated by the process of endocytosis and the uptake of paclitaxel was remarkably superior to Intaxel(TM) in all cell lines tested. Moreover, the intracellular uptake of paclitaxel in Nanoxel(TM)- and Abraxane(TM)-treated groups was comparable. Hence, the nanoparticle-based formulations of paclitaxel (Nanoxel(TM) and Abraxane(TM)) are endowed with higher efficiency to deliver the drug to target cells as compared to the conventional Cremophor-based formulation. CONCLUSION:Nanoxel(TM) appears to be of great promise in tumor targeting and may provide an advantage for paclitaxel delivery into cancer cells.
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