<p>Elaboration and characterization of curcumin-loaded Tri-CL-mPEG three-arm copolymeric nanoparticles by a microchannel technology</p>

Abstract

Purpose: Clinical applications of curcumin (Cur) have been greatly restricted due to its low solubility and poor systemic bioavailability. Three-arm amphiphilic copolymer tricarballylic acid-poly (ε-caprolactone)-methoxypolyethylene glycol (Tri-CL-mPEG) nanoparticles (NPs) were designed to improve the solubility and bioavailability of Cur. The present study adopted a microchannel system to precisely control the preparation of self-assembly polymeric NPs via liquid flow-focusing and gas displacing method. Methods: The amphiphilic three-arm copolymer Tri-CL-mPEG was synthesized and self-assembled into nearly spherical NPs, yielding Cur encapsulated into NP cores (Cur-NPs). The obtained NPs were evaluated for physicochemical properties, morphology, toxicity, cellular uptake by A549 cells, release in vitro, biodistribution, and pharmacokinetics in vivo. Results: Rapidly fabricated and isodispersed Cur-NPs prepared by this method had an average diameter of 116±3 nm and a polydispersity index of 0.197±0.008. The drug loading capacity and entrapment efficiency of Cur-NPs were 5.58±0.23% and 91.42±0.39%, respectively. In vitro release experiments showed sustained release of Cur, with cumulative release values of 40.1% and 66.1% at pH 7.4 and pH 5.0, respectively, after 10 days post-incubation. The results of cellular uptake, biodistribution, and in vivo pharmacokinetics experiments demonstrated that Cur-NPs exhibited better biocompatibility and bioavailability, while additionally enabling greater cellular uptake and prolonged circulation with possible spleen, lung, and kidney targeting effects when compared to the properties of free Cur. Conclusion: These results indicate that Tri-CL-mPEG NPs are promising in clinical applications as a controllable delivery system for hydrophobic drugs.

Curcumin-Loaded Hybrid Nanoparticles: Microchannel-Based Preparation and Antitumor Activity in a Mouse Model

“…Tri-CL-mPEG was synthesized as previously described, 38 and the reaction procedure is shown in Figure 1A . Specifically, 1,2,3-propanetricarboxylic acid, ε-caprolactone and Sn(Oct) 2 were allowed to react in a nitrogen atmosphere for 24 h at 120°C.…”

“…Tri-CL-mPEG was synthesized as previously described, 38 and the reaction procedure is shown in Figure 1A…”

Star polyester-based folate acid-targeting nanoparticles for doxorubicin and curcumin co-delivery to combat multidrug-resistant breast cancer

“…However, the emergence of MDR (by the P-gp pathway; Li et al, 2018 ), strong cell toxicity, and poor targeting selection have seriously hindered its clinical application. Curcumin (CUR) is a low-toxicity natural drug made of polyphenols extracted from Zingiberaceae plants (Wu et al, 2019 ) and is less effective against cancer than first-line chemotherapy but has broad-spectrum effects (Guo et al, 2018 ; Zhang et al, 2018 ; Barati et al, 2019 ; Guo et al, 2019 , 2020 ). Hou et al ( 2019 ) and Lv et al ( 2016 ) have shown that CUR is an excellent P-gp inhibitor that effectively maintains a high DOX concentration in drug-resistant human breast cancer MCF-7/ADR cells.…”

Matrix metalloprotein-triggered, cell penetrating peptide-modified star-shaped nanoparticles for tumor targeting and cancer therapy

“…In this study, we selected curcumin (Cur) for use as a model drug owing to its exceptional anti-cancer activity, safety profile, and lack of ability to induce multidrug resistance. However, its poor water solubility, poor absorption, and rapid clearance have greatly inhibited its clinical application [20]. To overcome these disadvantages of Cur, we aimed to develop an enzyme-triggered CPP-mediated NP (MePEG-Peptide-Tri-CL) to improve cancer chemotherapy using Cur.…”