Micellization of Antineoplastic Agent to Significantly Upregulate Efficacy and Security

Abstract

The amphiphilic diblock copolymer composed of methoxy poly(ethylene glycol) and racemic oligoleucine was synthesized which formed into micelle with uniform size in aqueous environment. Doxorubicin (DOX) was loaded into micelle aided by noncovalent interactions with high drug loading efficiency. The DOX-loaded micelle (referred as M-DOX) demonstrated the sustained drug release in vitro and excellent antiproliferative capability toward both MG63 and Saos-2 cells. Furthermore, for both MG63 and Saos-2-xenografted BALB/c nude mouse models, M-DOX exhibited enhanced intratumoral distribution, improved antitumor efficacy, and reduced side effects compared with free DOX. Therefore, the polypeptide micelle showed a bright prospect for controlled delivery of antitumor drugs in vivo.

Epirubicin-Complexed Polypeptide Micelle Effectively and Safely Treats Hepatocellular Carcinoma

“…Even dealt with the maximum concentration of 100.0 μg·mL −1 for 72 h, the cells could keep their viability for more than 90%. It indicated that the polypeptide-based block copolymer was a kind of safe materials for nanocarrier construction as reported previously [14,30]. On drug-related MTT assay, both free EPI and mPEG-b-PGA/EPI exhibited typically time-and agent concentration-dependent cytotoxicity effects ( Figure 6).…”

“…However, the increase amplitude in the mPEG-b-PGA/EPI group, whose red fluorescence intensity was nearly close to that of free EPI group, was more obviously. This might attribute to the increased endocytosis of loading micelle and the rapid EPI release in endosomes where the pH is much lower than that in normal physiological microenvironment, while free EPI effused quickly after uptake [30]. The date of FCM further confirmed the results of CLSM ( Figure 5).…”

“…To detect the influence of mPEG-b-PGA on the biodistribution of EPI, the ex vivo fluorescence imaging tests of isolated tumors and major organs (i.e., heart, liver, spleen, lung, and kidney) were performed at 6 or 12 h post-injection into H22 HCC-xenografted BALB/c mice. As shown in Figure 8, liver and kidney appeared strong EPI fluorescence after the administration of EPI formulations, suggesting that both of them were mainly metabolized by liver and kidney [17,30]. It is worth mentioning that the fluorescence intensities of tumor and test organs were observed to fall in the free EPI group when the time extended from 6 to 12 h, while that in the mPEG-b-PGA/EPI group increased somewhat.…”

Polymer Nanoparticle-Based Chemotherapy for Spinal Malignancies

“…The two studies described above indicate that the DOX-loaded nanoparticles can potentially be used to treat spinal malignancies, including primary (e.g., fibrosarcoma) and metastatic (e.g., breast cancer) ones. Additionally, Ding's group synthesized three poly(ethylene glycol)-polyleucine (PEG-PLeu) di-or triblock copolymers through ring-opening polymerization (ROP) of leucine N-carboxyanhydride (Leu NCA) with amino-terminated PEG as a macroinitiator [60,61]. DOX was loaded into micelles through a nanoprecipitation technique.…”

Nanoparticles for Improved Delivery of Poorly Soluble Drugs

“…pH-responsive polyion complex micelles [40,41], cholesterolenhanced, amphiphilic di, tri block copolymer [42][43][44], thermoresponsive polypeptide [45], galactopeptide micelles [37] have demonstrated enhanced cellular internalization and receptormediated tumor cellular proliferation inhibition in malignancy chemotherapy. PEG-PLGA copolymers have shown potential applications as drug delivery platforms in vivo with enhanced stabilities during circulation and accelerated drug release at targeting lesion sites [46,47].…”