Preparation and Evaluation of Doxorubicin-Loaded Micelles Based on Glycyrrhetinic Acid Modified Gelatin Conjugates for Targeting Hepatocellular Carcinoma

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent fatal diseases and the incidence of HCC is increasing worldwide. Polymeric micelles with targeting groups have drawn great attention as carriers for drug delivery in HCC therapy. Herein, novel glycyrrhetinic acid modified gelatin (GA-GEL) conjugates with three substitution degrees were synthesized and characterized. Doxorubicin (DOX) was applied as a model drug. DOX-loaded GA-GEL (DOX/GA-GEL) micelles were prepared by an emulsionsolvent evaporation method. The mean diameters of DOX/GA-GEL micelles were in the range of 195-235 nm. The encapsulation efficiency of DOX/GA-GEL micelles was 63.6%-96.2%, and the loading content was 8.3%-12.5%. Drug release from DOX-loaded micelles exhibited a biphasic manner in phosphate buffer solution (PBS) at pH 7.4. DOX/GA-GEL could be efficiently accumulated into human liver cancer HepG2 cells. The IC 50 values of DOX/GA-GEL-2 and DOX⋅HCl in HepG2 cells were 0.33 and 0.66 g/mL, respectively. In vivo imaging analysis demonstrated that the fluorescence signals of DiR-labeled GA-GEL-2 micelles were mainly distributed in liver and H22 orthotopic tumor, indicating that GA-GEL had the liver-targeting activity. Compared to DOX⋅HCl, DOX/GA-GEL-2 exhibited better antitumor activity in H22 orthotopic mice. Therefore, these results indicated that GA-GEL could be used as carrier of hydrophobic drug for targeting HCC.

Characterization and Evaluation of Bone-Derived Nanoparticles as a Novel pH-Responsive Carrier for Delivery of Doxorubicin into Breast Cancer Cells

“…Other DDSs for treating cancer including polymers, micelles, lipid, CeO 2 , etc. also exhibited good binding affinity for DOX [ 58 , 62 , 63 , 64 ].…”

Micellar Drug Delivery Systems Based on Natural Biopolymers

“…Furthermore, it appeared that these micelles exhibited higher cellular toxicity to MDA-MB-231 cancerous cells than in normal cells (NIH-3T3). Novel glycyrrhetinic acid modified gelatin (GA-Gel) conjugates with three substitution degrees were synthesized and used for the preparation of Dox-loaded micellar systems by an emulsion–solvent evaporation method [ 160 ]. The encapsulation efficiency was 63.6–96.2%, and the loading content was 8.3–12.5%.…”

Fabrication of novel combinatorial drug encapsulated micelles for enhanced tumor targeting in intestinal cancer in mouse model

“…The decades of nanoscale research has resulted in several nanotheranostics and nanotherapeutics techniques being developed for the treatment of cancer (Bertrand, Wu, Xu, Kamaly, & Farokhzad, 2014;D. Fan et al, 2018) nanoscale drug delivery system is the polymeric micelles which comprises a core (inner realm) and shell (outer realm; Bromberg, 2008;Ji et al, 2018;Kataoka, Harada, & Nagasaki, 2001).…”

“…Polymeric micelles have a unique advantage of being able to enclose the unstable drug in the core realm to avoid contact from the gastrointestinal contents which may damage or degrade it. Thus mixed micelles are being much sought after as they offer much‐needed stability of drug, improved release, and uptake of drug at the target tumor site, prolong its circulation time, and also are cytocompatible (Ebrahim Attia et al, ; D. Fan et al, ; Ji et al, ). Over decades, it has also been found that the micelles may reduce the potential side effects of the drug and thereby improve the therapeutic effects.…”

“…The decades of nanoscale research has resulted in several nanotheranostics and nanotherapeutics techniques being developed for the treatment of cancer (Bertrand, Wu, Xu, Kamaly, & Farokhzad, ; D. Fan et al, ). These are either being researched upon or have already reached the stage of clinical studies.…”