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Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid.

Li J, Chen T, Deng F, Wan J, Tang Y, Yuan P, Zhang L - Int J Nanomedicine (2015)

Bottom Line: Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface.Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups.Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis.

View Article: PubMed Central - PubMed

Affiliation: Chongqing Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

ABSTRACT
We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity.

No MeSH data available.


Related in: MedlinePlus

Effect of free GA on the ability of Ccn-BNP-GA to bind to HepG2 cells over 24 hours.Notes: *P<0.05 compared with Ccn-sus, #P<0.05 compared with free GA + Ccn-BNP-GA. The results are expressed as the mean ± standard deviation (n=3).Abbreviations: Ccn-sus, curcumin suspension; Ccn-BNPs, curcumin-loaded albumin nanoparticles; Ccn-BNP-GA, curcumin-loaded albumin nanoparticles surface-functionalized with GA; GA, glycyrrhetinic acid.
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f8-ijn-10-5475: Effect of free GA on the ability of Ccn-BNP-GA to bind to HepG2 cells over 24 hours.Notes: *P<0.05 compared with Ccn-sus, #P<0.05 compared with free GA + Ccn-BNP-GA. The results are expressed as the mean ± standard deviation (n=3).Abbreviations: Ccn-sus, curcumin suspension; Ccn-BNPs, curcumin-loaded albumin nanoparticles; Ccn-BNP-GA, curcumin-loaded albumin nanoparticles surface-functionalized with GA; GA, glycyrrhetinic acid.

Mentions: In this study, HPLC was used to measure intracellular drug concentrations and to detect whether the Ccn-loaded formulations could be endocytosed into HepG2 cells. As shown in Figure 8, the amounts of intracellular Ccn of Ccn suspension and Ccn-BNPs were 52.22±11.04 ng/105 cells and 56.10±11.57 ng/105 cells, respectively. However, Ccn-BNP-GA achieved a significantly higher drug concentration than non-conjugated nanoparticles probably because of the strong binding interactions between GA and its receptors. Further, we conducted a competitive binding experiment with addition of free GA in advance. As a consequence, the concentrations of Ccn decreased significantly in contrast with the groups without free GA. The presence of free GA as an inhibitor hindered the binding of GA to its receptors. The cell uptake results showed that Ccn-BNP-GA could be actively targeted to GA-positive cells.


Synthesis, characterization, and in vitro evaluation of curcumin-loaded albumin nanoparticles surface-functionalized with glycyrrhetinic acid.

Li J, Chen T, Deng F, Wan J, Tang Y, Yuan P, Zhang L - Int J Nanomedicine (2015)

Effect of free GA on the ability of Ccn-BNP-GA to bind to HepG2 cells over 24 hours.Notes: *P<0.05 compared with Ccn-sus, #P<0.05 compared with free GA + Ccn-BNP-GA. The results are expressed as the mean ± standard deviation (n=3).Abbreviations: Ccn-sus, curcumin suspension; Ccn-BNPs, curcumin-loaded albumin nanoparticles; Ccn-BNP-GA, curcumin-loaded albumin nanoparticles surface-functionalized with GA; GA, glycyrrhetinic acid.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556296&req=5

f8-ijn-10-5475: Effect of free GA on the ability of Ccn-BNP-GA to bind to HepG2 cells over 24 hours.Notes: *P<0.05 compared with Ccn-sus, #P<0.05 compared with free GA + Ccn-BNP-GA. The results are expressed as the mean ± standard deviation (n=3).Abbreviations: Ccn-sus, curcumin suspension; Ccn-BNPs, curcumin-loaded albumin nanoparticles; Ccn-BNP-GA, curcumin-loaded albumin nanoparticles surface-functionalized with GA; GA, glycyrrhetinic acid.
Mentions: In this study, HPLC was used to measure intracellular drug concentrations and to detect whether the Ccn-loaded formulations could be endocytosed into HepG2 cells. As shown in Figure 8, the amounts of intracellular Ccn of Ccn suspension and Ccn-BNPs were 52.22±11.04 ng/105 cells and 56.10±11.57 ng/105 cells, respectively. However, Ccn-BNP-GA achieved a significantly higher drug concentration than non-conjugated nanoparticles probably because of the strong binding interactions between GA and its receptors. Further, we conducted a competitive binding experiment with addition of free GA in advance. As a consequence, the concentrations of Ccn decreased significantly in contrast with the groups without free GA. The presence of free GA as an inhibitor hindered the binding of GA to its receptors. The cell uptake results showed that Ccn-BNP-GA could be actively targeted to GA-positive cells.

Bottom Line: Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface.Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups.Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis.

View Article: PubMed Central - PubMed

Affiliation: Chongqing Medicine Engineering Research Center, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, School of Pharmacy, Chongqing Medical University, Chongqing, People's Republic of China.

ABSTRACT
We have designed and developed curcumin (Ccn)-loaded albumin nanoparticles (BNPs) surface-functionalized with glycyrrhetinic acid (Ccn-BNP-GA) for GA receptor-mediated targeting. Ccn-BNP-GA was prepared by conjugating GA as a hepatoma cell-specific binding molecule onto the surface of BNPs. Ccn-BNP-GA showed a narrow distribution with an average size of 258.8±6.4 nm, a regularly spherical shape, an entrapment efficiency of 88.55%±5.54%, and drug loading of 25.30%±1.58%. The density of GA as the ligand conjugated to BNPs was 140.48±2.784 μg/g bovine serum albumin. Cytotoxicity assay results indicated that Ccn-BNP-GA was significantly more cytotoxic to HepG2 cells and in a concentration-dependent manner. Ccn-BNP-GA also appeared to be taken up to a greater extent by HepG2 cells than undecorated groups, which might be due to the high affinity of GA for GA receptors on the HepG2 cell surface. These cytotoxicity assay results were corroborated by analysis of cell apoptosis and the cell cycle. Further, Ccn-BNP-GA showed an approximately twofold higher rate of cell apoptosis than the other groups. Moreover, proliferation of HepG2 cells was arrested in G2/M phase based on cell cycle analysis. These results, which were supported by the GA receptor-mediated endocytosis mechanism, indicate that BNPs surface-functionalized with GA could be used in targeted cancer treatment with high efficacy, sufficient targeting, and reduced toxicity.

No MeSH data available.


Related in: MedlinePlus