Coencapsulated Doxorubicin and Bromotetrandrine Lipid Nanoemulsions in Reversing Multidrug Resistance in Breast Cancer in Vitro and in Vivo

Abstract

Multidrug resistance has remained a major cause of treatment failure in chemotherapy due to the presence of P-glycoproteins (P-gp) that actively pump drugs from inside the cell to the outside. P-gp inhibitors were developed and coadministered with chemotherapeutic drugs to overcome the effect of efflux pumps thus enhancing the chemosensitivity of therapeutics. Our study aimed at developing a lipid nanoemulsion system for the coencapsulation of doxorubicin (DOX) and bromotetrandrine (W198) to reverse multidrug resistance (MDR) in breast cancer. W198 was a potent P-gp inhibitor, and DOX was selected as a model compound which is a common substrate for P-gp. Coencapsulated DOX and W198 lipid nanoemulsions (DOX/W198-LNs) displayed significantly enhanced cytotoxicity in DOX-resistant human breast cancer cells (MCF-7/ADR) compared with DOX loaded lipid nanoemulsions (DOX-LNs) (p < 0.05), which is due to the enhanced intracellular uptake of DOX in MCF-7/ADR cells. The biodistribution study was performed using a nude mice xenograft model, which demonstrates enhanced tumor uptake of DOX in the DOX/W198-LN treated group. Compared with DOX solution, DOX/W198-LNs showed reduced cardiac toxicity and gastrointestinal injury in rats. Taken together, DOX/W198-LNs represent a promising formulation for overcoming MDR in breast cancer.

The chemotherapeutic potential of doxorubicin-loaded PEG-b-PLGA nanopolymersomes in mouse breast cancer model

“…Nanocarriers, especially polymeric NPs, can significantly enhance the anti-tumor efficiency of various chemotherapeutic drugs based on the enhanced permeation and retention (EPR) effect [14][15][16][17][18].…”

Targeted delivery of celastrol to mesangial cells is effective against mesangioproliferative glomerulonephritis

“…The ability of CLT and CLT-AN to induce apoptosis in HBZY-1 cells was measured quantitatively based on FITC-Annexin V and PI double staining 63 . HBZY-1 cells were seeded in the same way as for the cell cycle distribution assay.…”

<p>Paclitaxel-Loaded Macrophage Membrane Camouflaged Albumin Nanoparticles for Targeted Cancer Therapy</p>

“…Nanoparticles have high drug-loading capacity, good storage stability, enhanced cytotoxicity, and may circumvent the multidrug resistance in tumor cells. [8][9][10][11] With a well-designed nanoparticle shell, drug-loaded nanoparticles are indicated to prolong the circulation of small molecule drugs in the blood circulation, which could facilitate the extravasation and passive targeting to the tumor site with an enhanced permeability and retention effect. 11,12 To achieve tumor-targeted drug delivery, a common strategy is to modify nanoparticles with targeting ligands such as antibodies and peptides.…”