Biodegradable polymeric micelles coencapsulating paclitaxel and honokiol: a strategy for breast cancer therapy in vitro and in vivo

Abstract

The combination of chemotherapy drugs attracts more attention in clinical cancer trials. However, the poor water solubility of chemotherapeutic drugs restricts their anticancer application. In order to improve antitumor efficiency and reduce side effects of free drugs, we prepared paclitaxel (PTX) and honokiol (HK) combination methoxy poly(ethylene glycol)–poly(caprolactone) micelles (P–H/M) by solid dispersion method against breast cancer. The particle size of P–H/M was 28.7±2.5 nm, and transmission electron microscope image confirmed that P–H/M were spherical in shape with small particle size. After being encapsulated in micelles, the release of PTX or HK showed a sustained behavior in vitro. In addition, both the cytotoxicity and the cellular uptake of P–H/M were increased in 4T1 cells, and P–H/M induced more apoptosis than PTX-loaded micelles or HK-loaded micelles, as analyzed by flow cytometry assay and Western blot. Furthermore, the antitumor effect of P–H/M was significantly improved compared with PTX-loaded micelles or HK-loaded micelles in vivo. P–H/M were more effective in inhibiting tumor proliferation, inducing tumor apoptosis, and decreasing the density of microvasculature. Moreover, bioimaging analysis showed that drug-loaded polymeric micelles could accumulate more in tumor tissues compared with the free drug. Our results suggested that P–H/M may have potential applications in breast cancer therapy.

Honokiol: A Review of Its Anticancer Potential and Mechanisms

“…Due to the low water solubility and bioavailability of honokiol, multiple studies have been performed to develop proper honokiol delivery systems to improve its pharmacological effectiveness. A few studies have been performed to develop efficient drug carriers to deliver honokiol to its respective target, including the development of nanoparticles [224][225][226], micelles [227][228][229], and liposomes [73,171,223].…”

“…Wang et al [228] prepared paclitaxel (PTX) and honokiol (HK) combination methoxy poly(ethylene glycol) poly(caprolactone) micelles (P-H/M) via the solid dispersion method against breast cancer (4T1). The particle size of P-H/M was 28.7 ± 2.5 nm and spherical in shape.…”

Surface-enhanced Raman scattering investigation of targeted delivery and controlled release of gemcitabine

“…Additionally, through multifunctionalization, nanocarriers can contain not only anticancer payloads but also ligands that preferentially bind to surface receptor proteins of cancer cells and mediate endocytosis of the nanocarrier. These key advantages have recently attracted considerable interest 7764 santiago et al and led to the development of various nanocarrier-based systems, including micellar, [11][12][13] liposome, 14,15 polymer, [16][17][18] noble metal, 4,5,19 and other 2,20 nanocarriers. Here, we present an investigation into a nanocarrier-based targeted drug delivery system for the anticancer drug gemcitabine (GEM) administration.…”

Dual tumor-targeted poly(lactic-<em>co</em>-glycolic acid)&ndash;polyethylene glycol&ndash;folic acid nanoparticles: a novel biodegradable nanocarrier for secure and efficient antitumor drug delivery

“…In the last few decades, rapid development of biodegradable polymeric carriers has attracted considerable attention, because of their versatile functional construction and biocompatibility for wide applications in biomedicine, such as drug delivery, gene delivery, tissue engineering, diagnosis, antibacterial/antifouling properties, and medical devices. [1][2][3][4][5][6][7][8][9] With regard to security, with rational design, biodegradable polymeric carriers are able to degrade into friendly biological catabolites, which is particularly important to reduce systemic cytotoxicity caused by the carrier. On the other hand, simplex biodegradable carriers cannot always meet rigorous demands, owing to the extremely hostile and complex environments in vivo.…”