Tannic acid-inspired paclitaxel nanoparticles for enhanced anticancer effects in breast cancer cells.

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ID: 99424
2019
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Abstract
Paclitaxel (PTX) is a gold standard chemotherapeutic agent for breast, ovarian, pancreatic and non-small cell lung carcinoma. However, in clinical use PTX can have adverse side effects or inadequate pharmacodynamic parameters, limiting its use. Nanotechnology is often employed to reduce the therapeutic dosage required for effective therapy, while also minimizing the systemic side effects of chemotherapy drugs. However, there is no nanoformulation of paclitaxel with chemosensitization motifs built in. With this objective, we screened eleven pharmaceutical excipients to develop an alternative paclitaxel nanoformulation using a self-assembly method. Based on the screening results, we observed tannic acid possesses unique properties to produce a paclitaxel nanoparticle formulation, i.e., tannic acid-paclitaxel nanoparticles. This stable TAP nanoformulation, referred to as TAP nanoparticles (TAP NPs), showed a spherical shape of ~ 102 nm and negative zeta potential of ~ -8.85. The presence of PTX in TAP NPs was confirmed by Fourier Transform Infrared (FTIR) spectra, thermogravimetric analyzer (TGA), and X-ray diffraction (XRD). Encapsulation efficiency of PTX in TAP NPs was determined to be ≥96%. Intracellular drug uptake of plain drug PTX on breast cancer cells (MDA-MB-231) shows more or less constant drug levels in 2 to 6 h, suggesting drug efflux by the P-gp transporters, over TAP NPs, in which PTX uptake was more than 95.52 ± 11.01% in 6 h, as analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Various biological assays such as proliferation, clonogenic formation, invasion, and migration confirm superior anticancer effects of TAP NPs over plain PTX at all tested concentrations. P-gp expression, beta-tubulin stabilization, Western blot, and microarray analysis further confirm the improved therapeutic potential of TAP NPs. These results suggest that the TAP nanoformulation provides an important reference for developing a therapeutic nanoformulation affording pronounced, enhanced effects in breast cancer therapy.
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chowdhury2019tannicjournal Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Chowdhury, Pallabita;Nagesh, Prashanth K B;Hatami, Elham;Wagh, Santosh;Dan, Nirnoy;Tripathi, Manish K;Khan, Sheema;Hafeez, Bilal B;Meibohm, Bernd;Chauhan, Subhash C;Jaggi, Meena;Yallapu, Murali M;
Journal Journal of colloid and interface science
Year 2019
DOI
S0021-9797(18)31148-2
URL
Keywords
Breast cancer nanoparticles drug delivery paclitaxel nanomedicine tannic acid cancer therapeutics

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