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PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers.
Biomaterials 2013; 34(5):1591-600B

Abstract

Paclitaxel (PTX) is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its therapeutic benefit is often limited by severe side effects. We have developed a micelle-based PTX formulation based on a simple conjugate derived from polyethylene glycol 5000 (PEG(5K)) and embelin (EB). Embelin is a natural product and exhibits antitumor activity through blocking the activity of X-linked inhibitor of apoptosis protein (XIAP). PEG(5K)-EB₂ conjugate self-assembles to form stable micelles in aqueous solution and efficiently encapsulates hydrophobic drugs such as PTX. PEG(5K)-EB₂ micelles have a relatively low CMC of 0.002 mg/mL (0.35 μM) with sizes in the range of 20 ∼ 30 nm with or without loaded PTX. In vitro cell uptake study showed that the PEG(5K)-EB₂ micelles were efficiently taken up by tumor cells. In vitro release study showed that PTX formulated in PEG(5K)-EB₂ micelles was slowly released over 5 days with much slower release kinetics than that of Taxol formulation. PTX formulated in PEG(5K)-EB₂ micelles exhibited more potent cytotoxicity than Taxol in several cultured tumor cell lines. Total body near infrared fluorescence (NIRF) imaging showed that PEG(5K)-EB₂ micelles were selectively accumulated at tumor site with minimal uptake in major organs including liver and spleen. PTX-loaded PEG(5K)-EB₂ micelles demonstrated an excellent safety profile with a maximum tolerated dose (MTD) of 100-120 mg PTX/kg in mice, which was significantly higher than that for Taxol (15-20 mg PTX/kg). Finally, PTX formulated in PEG(5K)-EB₂ micelles showed superior antitumor activity compared to Taxol in murine models of breast and prostate cancers.

Authors+Show Affiliations

Center for Pharmacogenetics, University of Pittsburgh School of Pharmacy, Pittsburgh, PA 15261, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

23182923

Citation

Lu, Jianqin, et al. "PEG-derivatized Embelin as a Nanomicellar Carrier for Delivery of Paclitaxel to Breast and Prostate Cancers." Biomaterials, vol. 34, no. 5, 2013, pp. 1591-600.
Lu J, Huang Y, Zhao W, et al. PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. Biomaterials. 2013;34(5):1591-600.
Lu, J., Huang, Y., Zhao, W., Marquez, R. T., Meng, X., Li, J., ... Li, S. (2013). PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. Biomaterials, 34(5), pp. 1591-600. doi:10.1016/j.biomaterials.2012.10.073.
Lu J, et al. PEG-derivatized Embelin as a Nanomicellar Carrier for Delivery of Paclitaxel to Breast and Prostate Cancers. Biomaterials. 2013;34(5):1591-600. PubMed PMID: 23182923.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - PEG-derivatized embelin as a nanomicellar carrier for delivery of paclitaxel to breast and prostate cancers. AU - Lu,Jianqin, AU - Huang,Yixian, AU - Zhao,Wenchen, AU - Marquez,Rebecca T, AU - Meng,Xiaojie, AU - Li,Jiang, AU - Gao,Xiang, AU - Venkataramanan,Raman, AU - Wang,Zhou, AU - Li,Song, Y1 - 2012/11/23/ PY - 2012/09/18/received PY - 2012/10/30/accepted PY - 2012/11/28/entrez PY - 2012/11/28/pubmed PY - 2013/5/17/medline SP - 1591 EP - 600 JF - Biomaterials JO - Biomaterials VL - 34 IS - 5 N2 - Paclitaxel (PTX) is one of the most effective chemotherapeutic agents for a wide spectrum of cancers, but its therapeutic benefit is often limited by severe side effects. We have developed a micelle-based PTX formulation based on a simple conjugate derived from polyethylene glycol 5000 (PEG(5K)) and embelin (EB). Embelin is a natural product and exhibits antitumor activity through blocking the activity of X-linked inhibitor of apoptosis protein (XIAP). PEG(5K)-EB₂ conjugate self-assembles to form stable micelles in aqueous solution and efficiently encapsulates hydrophobic drugs such as PTX. PEG(5K)-EB₂ micelles have a relatively low CMC of 0.002 mg/mL (0.35 μM) with sizes in the range of 20 ∼ 30 nm with or without loaded PTX. In vitro cell uptake study showed that the PEG(5K)-EB₂ micelles were efficiently taken up by tumor cells. In vitro release study showed that PTX formulated in PEG(5K)-EB₂ micelles was slowly released over 5 days with much slower release kinetics than that of Taxol formulation. PTX formulated in PEG(5K)-EB₂ micelles exhibited more potent cytotoxicity than Taxol in several cultured tumor cell lines. Total body near infrared fluorescence (NIRF) imaging showed that PEG(5K)-EB₂ micelles were selectively accumulated at tumor site with minimal uptake in major organs including liver and spleen. PTX-loaded PEG(5K)-EB₂ micelles demonstrated an excellent safety profile with a maximum tolerated dose (MTD) of 100-120 mg PTX/kg in mice, which was significantly higher than that for Taxol (15-20 mg PTX/kg). Finally, PTX formulated in PEG(5K)-EB₂ micelles showed superior antitumor activity compared to Taxol in murine models of breast and prostate cancers. SN - 1878-5905 UR - https://www.unboundmedicine.com/medline/citation/23182923/PEG_derivatized_embelin_as_a_nanomicellar_carrier_for_delivery_of_paclitaxel_to_breast_and_prostate_cancers_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0142-9612(12)01239-2 DB - PRIME DP - Unbound Medicine ER -