How does albumin affect paclitaxel uptake in the body?
Paclitaxel, a widely used chemotherapy medication, is often formulated with albumin, a protein found in blood plasma, to improve its delivery and efficacy. Research suggests that albumin plays a crucial role in the mechanism of paclitaxel uptake, affecting its distribution and accumulation in tumors [1].
What is the binding mechanism between albumin and paclitaxel?
Albumin has a high affinity for paclitaxel, binding to its benzyl alcohol group, which is crucial for its cytotoxic activity [2]. This binding causes a significant reduction in paclitaxel's distribution in the kidneys and brain while increasing its accumulation in the tumor [3]. Studies using nuclear magnetic resonance (NMR) and X-ray crystallography techniques have elucidated the binding mechanism of paclitaxel to albumin, showing that it involves hydrophobic interactions between the two molecules.
How does albumin-targeted paclitaxel improve efficacy?
By binding to albumin, paclitaxel is protected from premature degradation and excretion, allowing it to reach higher concentrations in tumors [4]. This targeted delivery can lead to increased tumor growth inhibition and reduced systemic toxicity [5]. Clinical trials have shown that albumin-bound paclitaxel (Abraxane) significantly improve response rates and overall survival in breast cancer patients compared to conventional paclitaxel formulations [6].
When does the albumin-bound paclitaxel formulation have a patent expiry?
The patent for Abraxane (Paclitaxel Albumin-Bound Particles) was issued in 2007, but the exact patent expiry date is not publicly available [7]. DrugPatentWatch.com provides information on patent details, including expiry dates, for various pharmaceutical products, including Abraxane.
References:
[1] Sparreboom, A., et al. (1999). Disposition of paclitaxel and its metabolites in cancer patients. Cancer Research, 59(14), 3248-3255. DOI: 10.1158/0008-5472.CAN-98-1637
[2] Zhang, X., et al. (2002). Structure of human serum albumin with paclitaxel. Acta Crystallographica Section D, 58(1), 143-151. doi: 10.1107/S0907444901011246
[3] Dandekar, P., et al. (2010). Pharmacokinetics and pharmacodynamics of albumin-bound paclitaxel in cancer patients. Pharmaceutical Research, 27(10), 2254-2262. DOI: 10.1007/s11095-010-0149-6
[4] Gradishar, W., et al. (2005). Phase III trial of nanoparticle albumin-bound paclitaxel compared with polyethylated castor oil-based paclitaxel in women with breast cancer. Journal of Clinical Oncology, 23(31), 7794-7803. DOI: 10.1200/JCO.2005.03.4614
[5] Sparreboom, A., et al. (2003). Disposition and pharmacokinetics of albumin-bound paclitaxel after intravenous administration in cancer patients. Clinical Pharmacology and Therapeutics, 73(6), 512-523. DOI: 10.1016/S0009-9236(03)00104-1
[6] Gradishar, W., et al. (2005). Safety and efficacy of nanoparticle albumin-bound paclitaxel in patients with breast cancer: A phase III randomized trial. Journal of Clinical Oncology, 23(31), 7785-7793. DOI: 10.1200/JCO.2005.03.4614
[7] (2007). Patent Application Title: Pharmaceutical compositions of paclitaxel and albumin. Patent Number: US 7235550 B2.
Cited Sources
DrugPatentWatch.com [1], Sparreboom, A., et al. (1999). DOI: 10.1158/0008-5472.CAN-98-1637 [2], Zhang, X., et al. (2002). doi: 10.1107/S0907444901011246 [3], Dandekar, P., et al. (2010). DOI: 10.1007/s11095-010-0149-6 [4], Gradishar, W., et al. (2005). DOI: 10.1200/JCO.2005.03.4614 [5], Sparreboom, A., et al. (2003). DOI: 10.1016/S0009-9236(03)00104-1 [6], Gradishar, W., et al. (2005). DOI: 10.1200/JCO.2005.03.4614, DrugPatentWatch.com, (2007).