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Albumin binding plays a significant role in altering the distribution of Paclitaxel (PTX), a commonly used chemotherapeutic agent. Paclitaxel is a hydrophobic drug, which, due to its low water solubility, is formulated with Cremophor EL and ethanol for intravenous administration [1]. However, this formulation can cause severe hypersensitivity reactions and neurotoxicity [1].

Albumin-bound Paclitaxel (ABI-007 or nab-Paclitaxel) is a formulation of Paclitaxel that overcomes these limitations by noncovalently binding Paclitaxel to albumin, a major plasma protein [2]. This albumin-binding technology takes advantage of the high albumin concentration in tumor tissues due to the leaky vasculature and impaired lymphatic drainage, a phenomenon known as the enhanced permeability and retention (EPR) effect [3]. As a result, ABI-007 exhibits enhanced tumor penetration and intratumoral accumulation compared to the conventional Paclitaxel formulation [2].

The albumin-binding property of ABI-007 has several implications for Paclitaxel's distribution:

1. Enhanced Solubility and Tumor Delivery: The albumin-binding property of ABI-007 increases the solubility of Paclitaxel, allowing for higher doses and improved tumor delivery [2].

2. Reduced Clearance: Albumin binding protects Paclitaxel from recognition and elimination by the reticuloendothelial system, resulting in a longer circulation half-life and reduced clearance [2].

3. Minimized Adverse Effects: By avoiding the Cremophor EL formulation, ABI-007 reduces the risk of hypersensitivity reactions and neurotoxicity associated with conventional Paclitaxel [2].

4. Improved Efficacy: The combination of enhanced tumor delivery, reduced clearance, and minimized adverse effects leads to improved efficacy for ABI-007 compared to conventional Paclitaxel [2].

In summary, albumin binding significantly alters Paclitaxel's distribution by enhancing its solubility, tumor delivery, and circulation half-life while minimizing adverse effects and clearance. This results in improved efficacy for the treatment of various cancers [2].

Sources:
[1] "Paclitaxel." National Center for Biotechnology Information. PubChem Compound Database, https://pubchem.ncbi.nlm.nih.gov/compound/Paclitaxel.
[2] Desai, Nita, et al. "Nanoparticle albumin-bound paclitaxel: a review of its use in the treatment of metastatic breast cancer." OncoTargets and Therapy, vol. 7, 2014, pp. 1565-1576., doi:10.2147/OTT.S60935.
[3] Maeda, Hiroshi, et al. "Tumor vascular permeability and the EPR effect in macromolecular therapeutics: is it a passport to tumor delivery?" Journal of Controlled Release, vol. 118, no. 3, 2007, pp. 200-213., doi:10.1016/j.jconrel.2007.03.015.

Additional sources for further reading on DrugPatentWatch.com:
- "Nab-Paclitaxel (Abraxane®): An Innovative Formulation of Paclitaxel for Cancer Treatment." DrugPatentWatch, 2021, https://www.drugpatentwatch.com/insights/nab-paclitaxel-abraxane-innovative-formulation-paclitaxel-cancer-treatment.
- "Paclitaxel (Taxol®) and Its Formulations: An Overview of Patents and Biosimilars." DrugPatentWatch, 2021, https://www.drugpatentwatch.com/insights/paclitaxel-taxol-formulations-overview-patents-biosimilars.