Abstract
As per the World Health Organization, cancer is the second leading cause of death globally and is responsible for an estimated 9.6 million deaths in 2018. More than 2 million cases of lung and breast cancer have been reported in 2018. Paclitaxel is a natural product based anti-mitotic agent useful for the treatment of lung cancer, ovarian cancer and breast cancer. Paclitaxel exhibits low oral bioavailability due to poor aqueous solubility and poor permeability. Paclitaxel is the first blockbuster anticancer drug with annual sales of more than US $1 billion in 1997. Taxol®, Abraxane® and Genexol PM® are commercial injectable preparations of paclitaxel with a drug loading of not more than 17% w/w. The toxicity issues of Cremophor® EL used in Taxol® led to the development of different delivery systems sans Cremophor® EL. The maximum tolerated dose of Taxol® is 135 mg/m2. Taxol® exhibited hypersensitivity reactions and required use of special IVEX-2 filter to avoid leaching of plasticizer into the product. Genexol PM® was physically unstable and was ineffective against multidrug-resistant tumor treatment. Abraxane® exhibited limited tumor exposure, tumor uptake, tumor regression and higher half-maximal inhibitory concentration.
In this chapter, we reviewed the literature of paclitaxel delivery systems. Micelles, liposomes, nanoparticles, lipid systems, microparticles, emulsions, solid dispersions, cyclodextrin complexes, implants, prodrugs and hybrid systems have been reported for paclitaxel delivery. The major points of our analysis of the literature are (1) Efficiency of solubility enhancement of paclitaxel was found in the decreasing order for prodrugs, mixed micelles, cyclodextrin complexes and solid dispersions, (2) The oral bioavailability enhancement for nanoparticles, micelles and emulsions of paclitaxel was found to be 7-fold, 5-fold and 4-fold respectively, (3) Decreasing order of reduction in tumor growth was found in emulsion, liposome, prodrug and nanoparticulate delivery system of paclitaxel as compared to that with Taxol®, (4) Genexol PM® and Abraxane® do not require special filters to avoid leaching of plasticizer into the product, (5) Genexol PM® and Abraxane® being free from Cremophor® EL do not exhibit hypersensitivity reaction, (6) Paclitaxel mixed micelles composed of poly (ethylene glycol-co-lactic acid) and D-α-tocopheryl polyethylene glycol 1000 succinate were effective against multidrug-resistant tumor cells in contrast to Genexol PM®, (7) Recombinant chimeric polypeptide conjugated paclitaxel nanoparticles exhibited 2-fold systemic tumor exposure, tumor uptake as compared to Abraxane® and almost complete tumor regression, (8) Paclitaxel loaded polycaprolactone-co-D-α-tocopheryl polyethylene glycol 1000 succinate nanoparticles exhibited 8-fold lower half maximal inhibitory concentration as compared to Abraxane®, (9) Paclitaxel delivery systems such as implants, nanoparticles, solid dispersions, lipid nanoparticles and micelles have been reported with more than 20% drug loading, (10) The maximum tolerated dose of Genexol PM® and Abraxane® could be increased from 135 mg/m2 to 300 mg/m2, and (11) Orally effective paclitaxel formulations such as DHP107 and Oraxol® are under phase II clinical trials.
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The authors PA, SK, KV acknowledge scholarship provided by Department of Pharmaceuticals, Government of India.
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A, P., Kar, S., Vignesh, K., Kolhe, U.D. (2020). An Overview of Paclitaxel Delivery Systems. In: Saneja, A., Panda, A., Lichtfouse, E. (eds) Sustainable Agriculture Reviews 43. Sustainable Agriculture Reviews, vol 43. Springer, Cham. https://doi.org/10.1007/978-3-030-41838-0_6
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