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|Title:||Paclitaxel-loaded PLGA nanoparticles: Potentiation of anticancer activity by surface conjugation with wheat germ agglutinin||Authors:||Mo, Y.
Isopropyl myristate (IPM)
Wheat germ agglutinin (WGA)
|Issue Date:||28-Nov-2005||Citation:||Mo, Y., Lim, L.-Y. (2005-11-28). Paclitaxel-loaded PLGA nanoparticles: Potentiation of anticancer activity by surface conjugation with wheat germ agglutinin. Journal of Controlled Release 108 (2-3) : 244-262. ScholarBank@NUS Repository. https://doi.org/10.1016/j.jconrel.2005.08.013||Abstract:||Purpose: To potentiate the anticancer activity of paclitaxel-loaded PLGA nanoparticles through surface conjugation with wheat germ agglutinin (WGA). Methods: PLGA nanoparticles loaded with paclitaxel and isopropyl myristate (IPM) as release modifier were prepared by a solvent evaporation method. WGA was conjugated to the nanoparticle surface to give novel WIT-NP of 330 ± 3 nm. In vitro cytotoxicity of WIT-NP against malignant (A549 and H1299) and normal (CCL-186) pulmonary cell lines was evaluated alongside control formulations. IC50 doses were determined by the MTT assay, while cellular apoptosis was detected by cell nuclei staining and DeadEnd™ Fluorometric TUNEL assay. Cell cycle arrest was confirmed by flow cytometry. Cellular uptake of 3[H]-paclitaxel from the test and control formulations was also quantified. In vivo anticancer efficacy was evaluated in the SCID mice model engrafted with the A549 tumor nodule. Results: WIT-NP had superior anti-proliferation activity against the A549 and H1299 cell lines compared with conventional paclitaxel formulations as measured by IC50 doses. This was attributed to a more efficient intracellular accumulation of paclitaxel via WGA-receptor-mediated endocytosis and IPM-facilitated intracellular paclitaxel release. WIT-NP activity was associated with paclitaxel-induced apoptosis and cell arrest in the G2/M phase. A single intratumoral injection of WIT-NP at paclitaxel dose of 10 mg/kg inhibited the growth of A549 tumor nodules without inducing significant weight loss in the SCID mice over a period of 25 days. Tumor doubling time was greater than 25 days, compared with 11 days for nodules treated with conventional paclitaxel formulation. Conclusion: The formulation of WIT-NP, in which WGA is conjugated to the surface of paclitaxel and IPM-loaded PLGA nanoparticles, significantly potentiates the anticancer activity of paclitaxel.||Source Title:||Journal of Controlled Release||URI:||http://scholarbank.nus.edu.sg/handle/10635/106194||ISSN:||01683659||DOI:||10.1016/j.jconrel.2005.08.013|
|Appears in Collections:||Staff Publications|
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