Biodegradable micelles enhance the antiglioma activity of curcumin in vitro and in vivo

Abstract

Curcumin (Cur), a natural polyphenol of Curcuma longa , has been recently reported to possess antitumor activities. However, due to its poor aqueous solubility and low biological availability, the clinical application of Cur is quite limited. The encapsulation of hydrophobic drugs into nanoparticles is an effective way to improve their pharmaceutical activities. In this research, nanomicelles loaded with Cur were formulated by a self-assembly method with biodegradable monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs). After encapsulation, the cellular uptake was increased and Cur could be released from MPEG-PLA micelles in a sustained manner. The Cur-loaded MPEG-PLA micelles (Cur/MPEG-PLA micelles) exhibited an enhanced toxicity on C6 and U251 glioma cells and induced more apoptosis on C6 glioma cells compared with free Cur. Moreover, the therapy efficiency of Cur/MPEG-PLA micelles was evaluated at length on a nude mouse model bearing glioma. The Cur/MPEG-PLA micelles were more effective on suppressing tumor growth compared with free Cur, which indicated that Cur/MPEG-PLA micelles improved the antiglioma activity of Cur in vivo. The results of immunohistochemical and immunofluorescent analysis indicated that the induction of apoptosis, antiangiogenesis, and inhibition of cell proliferation may contribute to the improvement in antiglioma effects. Our data suggested that Cur/MPEG-PLA may have potential clinic applications in glioma therapy.

Preventive Effect of Curcumin Against Chemotherapy-Induced Side-Effects

“…Up to now, some inorganic and organic materials including iron oxide, silicon dioxide, ferritin, albumin, chitosan, oligosaccharides, cyclodextrin (CD), PAMAM dendrimers, poly (lactide-co-glycolide) (PLGA), poly(alkyl cyanoacrylate) (PACA), d-α-tocopheryl polyethylene glycol 1000-block-poly (β-amino ester) (TPGS-PAE), and monomethoxy poly(ethylene glycol)-poly(lactide) copolymers (MPEG-PLAs) have been used to fabricate curcumin nanoformulations ( Acharya and Sahoo, 2011 ; Cui et al, 2013 ; Dilnawaz and Sahoo, 2013 ; Mollazade et al, 2013 ; Chen et al, 2014 ; Fang et al, 2014 ; Lou et al, 2014 ; Sankar et al, 2014 ; Poorghorban et al, 2015 ; Scarano et al, 2015 ; Wang et al, 2015 ; Chen et al, 2016 ; de Oliveira et al, 2016 ; Ndong Ntoutoume et al, 2016 ; Pawar et al, 2016b ; Zheng et al, 2016 ; Zhang et al, 2017 ; Yadav et al, 2018 ). These as-prepared curcumin nanoformulations have been proven to have enhanced anticancer efficacy as well as significant improvement in bioavailability and retention time ( Pramanik et al, 2012 ; Zheng et al, 2016 ; Falconieri et al, 2017 ; Thulasidasan et al, 2017 ). Zhang et al (2017) reported that a nanoparticle containing curcumin and DOX enhanced anticancer efficacy of DOX and reduced its systematic toxicity.…”

Curcumin Delays Retinal Degeneration by Regulating Microglia Activation in the Retina of rd1 Mice

“…In addition, Ayadi synthesized nanoparticles less than 10 nm in size to enable them to be excreted from the renal system and easily reach the necessary location [68]. Curcumin-loaded nanoparticles have already been used in several animal models of disease, especially cancer [68-74]. …”

Poly(Ethylene Glycol)–Polylactide Micelles for Cancer Therapy

“…Moreover, compared to free Cur, they induced more apoptosis on C6 glioma cells. The Cur-loaded micelles also effectively improved the anti-glioma activity of Cur in vivo (Zheng et al, 2016 ) (Figure 6 ). In another study, researchers constructed Cur-loaded pH-sensitive MPEG–PLAPAE micelles.…”

“…(B) In vitro release study and (C) representative images of subcutaneous tumors in each treatment group. Reproduced with permission from Zheng et al ( 2016 ).…”