Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

Abstract

Purpose Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)- block -poly ( d , l -lactide) (mPEG-PDLLA). Methods PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated. Results The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was −19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC 0−t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications. Conclusion These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.

Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

“…The improved anticancer efficiency of this CA-polymer micellar system has been determined in BEL7402 and A549 cell-bearing nude mice, and the underlying mechanisms were suggested including the size reduction and improved stability of micelles by adding CA, which make them favorable for passive targeting to the tumor. Besides, CA enhanced the circulation time of micelles in the bloodstream, but also affected the transmembrane permeability and thus enhanced the cellular uptake, which both favored the accumulation of micelles in tumors ( Zhang et al, 2017 ).…”

Folic Acid Conjugated Polyglutamic Acid Drug Vehicle Synthesis through Deep Eutectic Solvent for Targeted Release of Paclitaxel

“…These results are in accordance with the previous anti‐tumor activity studies: almost total inhibition of cell viability and high cellular uptake were achieved at 100μg/mL of PTX loaded polymeric micelles after 24 h incubation. The incorporation of NaC in these micelles enhanced cellular uptakes in tumor cells . Nanomicelles are generally internalized into the cells via phagocytosis or endocytosis .…”

Intelligent polymeric micelles for multidrug co-delivery and cancer therapy

“…Accordingly, various cancer-specific homing molecules modified PMs were designed for accurately co-delivery of multidrug [52,53]. Usually, these molecules were capable of specifically recognizing and target certain tumour-specific antigens and the receptor that are overexpressed by cancer cells but rarely expressed or under-expressed on normal cells [54,55].…”