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

Pallabita Chowdhury, Prashanth K.B. Nagesh, Elham Hatami, Santosh Wagh, Nirnoy Dan, Manish Tripathi, Sheema Khan, Bilal Hafeez, Bernd Meibohm, Subhash Chauhan, Meena Jaggi, Murali Yallapu

Research output: Contribution to journalArticle

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.

LanguageEnglish (US)
Pages133-148
Number of pages16
JournalJournal of Colloid and Interface Science
Volume535
DOIs
StatePublished - Feb 1 2019

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Drug dosage
Drug interactions
Medical nanotechnology
Chemotherapy
Tannins
Liquid chromatography
Paclitaxel
Drug delivery
Encapsulation
Flavonoids
Self assembly
Mass spectrometry
Cells
Nanoparticles
Pharmaceutical Preparations
Pharmacodynamics
Excipients
Zeta potential
Tubulin
Microarrays

All Science Journal Classification (ASJC) codes

  • Electronic, Optical and Magnetic Materials
  • Biomaterials
  • Surfaces, Coatings and Films
  • Colloid and Surface Chemistry

Cite this

Tannic acid-inspired paclitaxel nanoparticles for enhanced anticancer effects in breast cancer cells. / Chowdhury, Pallabita; Nagesh, Prashanth K.B.; Hatami, Elham; Wagh, Santosh; Dan, Nirnoy; Tripathi, Manish; Khan, Sheema; Hafeez, Bilal; Meibohm, Bernd; Chauhan, Subhash; Jaggi, Meena; Yallapu, Murali.

In: Journal of Colloid and Interface Science, Vol. 535, 01.02.2019, p. 133-148.

Research output: Contribution to journalArticle

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AU - Wagh, Santosh

AU - Dan, Nirnoy

AU - Tripathi, Manish

AU - Khan, Sheema

AU - Hafeez, Bilal

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AU - Jaggi, Meena

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