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

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.

SUBMITTER: Chowdhury P

PROVIDER: S-EPMC6992213 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Chowdhury Pallabita P Nagesh Prashanth K B PKB Hatami Elham E Wagh Santosh S Dan Nirnoy N Tripathi Manish K MK Khan Sheema S Hafeez Bilal B BB Meibohm Bernd B Chauhan Subhash C SC Jaggi Meena M Yallapu Murali M MM

Journal of colloid and interface science 20180922

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 buil ...[more]

PMID: 30292104

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Project description:Infection is the major cause of morbidity after breast implant surgery. Biodegradable medical-grade polycaprolactone (mPCL) scaffolds designed and rooted in evidence-based research offer a promising alternative to overcome the limitations of routinely used silicone implants for breast reconstruction. Nevertheless, as with any implant, biodegradable scaffolds are susceptible to bacterial infection too, especially as bacteria can rapidly colonize the biomaterial surface and form biofilms. Biofilm-related infections are notoriously challenging to treat and can lead to chronic infection and persisting inflammation of surrounding tissue. To date, no clinical solution that allows to efficiently prevent bacterial infection while promoting correct implant integration, has been developed. In this study, we demonstrated for the first time, to our knowledge that the physical immobilization of 1 and 5% human serum albumin (HSA) onto the surface of 3D printed macro- and microporous mPCL scaffolds, resulted in a reduction of Staphylococcus aureus colonization by 71.7 ± 13.6% and 54.3 ± 12.8%, respectively. Notably, when treatment of scaffolds with HSA was followed by tannic acid (TA) crosslinking/stabilization, uniform and stable coatings with improved antibacterial activity were obtained. The HSA/TA-coated scaffolds were shown to be stable when incubated at physiological conditions in cell culture media for 7 days. Moreover, they were capable of inhibiting the growth of S. aureus and Pseudomonas aeruginosa, two most commonly found bacteria in breast implant infections. Most importantly, 1%HSA/10%TA- and 5%HSA/1%TA-coated scaffolds were able to reduce S. aureus colonization on the mPCL surface, by 99.8 ± 0.1% and 98.8 ± 0.6%, respectively, in comparison to the non-coated control specimens. This system offers a new biomaterial strategy to effectively translate the prevention of biofilm-related infections on implant surfaces without relying on the use of prophylactic antibiotic treatment.

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

Publications

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

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