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. 2018 Apr 3:13:1945-1962.
doi: 10.2147/IJN.S153763. eCollection 2018.

In vitro/vivo drug release and anti-diabetic cardiomyopathy properties of curcumin/PBLG-PEG-PBLG nanoparticles

Fei Tong  1 , Rongkui Chai  1 , Haiying Jiang  1 , Bo Dong  1
Affiliations

In vitro/vivo drug release and anti-diabetic cardiomyopathy properties of curcumin/PBLG-PEG-PBLG nanoparticles

Fei Tong et al. Int J Nanomedicine. .

Retraction in

Abstract

Background: The objective of this study was to survey the therapeutic function of curcumin-encapsulated poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gammabenzyl l-glutamate) (PBLG-PEG-PBLG) (P) on diabetic cardiomyopathy (DCM) via cross regulation effect of calcium-sensing receptor (CaSR) and endogenous cystathionine-γ-lyase (CSE)/hydrogen sulfide (H2S).

Methods: Diabetic rats were preconditioned with 20 mg/kg curcumin or curcumin/P complex continuously for 8 weeks. The blood and myocardiums were collected, the level of serum H2S was observed, and the [Ca2+]i content was measured in myocardial cells, and hematoxylin-eosin, CaSR, CSE, and calmodulin (CaM) expression were detected.

Results: Both curcumin and curcumin/P pretreatment alleviated pathological morphological damage of myocardium, increased H2S and [Ca2+]i levels, and upregulated the expression of CaSR, CSE, and CaM as compared to DCM group, while curcumin/P remarkably augmented this effect.

Conclusion: PBLG-PEG-PBLG could improve water-solubility and bioactivity of curcumin and curcumin/PBLG-PEG-PBLG significantly alleviated diabetic cardiomyopathy.

Keywords: CSE; CaSR; PBLG-PEG-PBLG; curcumin; diabetic cardiomyopathy.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this study.

Figures

Figure 1
Figure 1
The structure of PBLG-PEG-PBLG (P). Abbreviation: P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly (gamma-benzyl l-glutamate).
Figure 2
Figure 2
The TEM images of P and curcumin/P. Notes: (A) TEM of PBLG-PEG-PBLG; (B) TEM of curcumin/PBLG-PEG-PBLG. Abbreviations: TEM, transmission electron microscopy; P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate).
Figure 3
Figure 3
The cumulative releasing profile of free curcumin and curcumin from curcumin/P complexes and results are expressed as mean ± standard deviation. Abbreviation: P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly (gamma-benzyl l-glutamate).
Figure 4
Figure 4
Blood curcumin concentrations of curcumin and curcumin from curcumin/P complexes in rats and results are expressed as mean ± standard deviation. Abbreviation: P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly (gamma-benzyl l-glutamate).
Figure 5
Figure 5
(A) Histopathologic assessment of myocardial damage; (B) blood glucose, Chol, and TG levels; (C) serum insulin level. Notes: (A) Light microscope images (×100) in Sham group (a), DM-4w group (b), and DM-8w group (c). The quantitative analysis of histopathologic assessment is shown in “d”. Results are expressed as mean ± SD. A significant increase from Sham group is denoted by *p<0.01, and a significant increase from DW-4w group is denoted by **p<0.01. (B) The blood of Sham, DM-4w, and DM-8w groups were collected, and the levels of blood glucose, Chol, and TG were measured. Results are expressed as mean ± SD. A significant increase from Sham group is denoted by *p<0.01, and a significant increase from DW-4w group is denoted by **p<0.01. (C) The blood of Sham, DM-4w, and DM-8w groups were collected and the levels of serum insulin were measured. Results are expressed as mean ± SD. A significant increase from Sham group is denoted by *p<0.01, and a significant increase from DW-4w groups is denoted by **p<0.01. Abbreviations: DM, diabetes mellitus; Chol, cholesterol; TG, triglyceride; SD, standard deviation.
Figure 6
Figure 6
(A) CaSR expression in Sham, DM-4w, and DM-8w groups; (B) CSE expression in Sham, DM-4w, and DM-8w groups; (C) CaSR expression in Sham and DM-8w+CaRS groups; (D) CSE expression in Sham and DM-8w+CaRS groups; (E) CSE expression in Sham and DM-8w+CaRS+PAG groups. Notes: (A) CaSR expression in Sham group (a), DM-4w group (b), and DM-8w group (c). The quantitative analysis of CaSR expression is shown in “d”. Results are expressed as mean ± SD. (B) CSE expression in Sham group (a), DM-4w group (b), and DM-8w group (c). The quantitative analysis of CSE expression is shown in “d”. Results are expressed as mean ± SD. (C) CaSR expression in Sham group (a), DM-8w+CaRS group (b). The quantitative analysis of CaSR expression is shown in “c”. Results are expressed as mean ± SD. (D) CSE expression in Sham group (a) and DM-8w+CaRS group (b). The quantitative analysis of CSE expression is shown in “c”. Results are expressed as mean ± SD. (E) CSE expression in Sham group (a) and DM-8w+CaRS+PAG group (b). The quantitative analysis of CSE expression is shown in “c”. Results are expressed as mean ± SD. Magnification is ×100. A significant decrease from Sham group is denoted by *p<0.01, and a significant decrease from DW-4w group is denoted by **p<0.01. Abbreviations: CaSR, calcium-sensing receptor; DM, diabetes mellitus; CSE, cystathionine-γ-lyase; CaRS, calcium-sensing receptor stimulator; PAG, DL-propargylglycine.
Figure 7
Figure 7
(A) Histopathologic assessment of myocardial damage; (B) CaSR expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (C) CSE expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (D) H2S level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (E) [Ca2+]i level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (F) CaM expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups. Notes: (A) Light microscope images (×100) in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of histopathological assessment is shown in “i”. The histopathologic damage in DM-8w group is higher than that in Sham group (p<0.01), and the histopathologic damage in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is lower than that in DM-8w group (p<0.01); the histopathologic damage in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly lower than that in DM-8w group (p<0.01). (B) CaSR expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/ P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CaSR expression is shown in “B-i”. The CaSR expression in DM-8w group is lower than that in Sham group (p<0.01), and the CaSR expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CaSR expression in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). (C) CSE expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CSE expression is shown in “C-i”. The CSE expression in DM-8w group is lower than that in Sham group (p<0.01), and the CSE expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CSE expression in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). (D) The blood of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups were collected and the levels of H2S were measured. Results are expressed as mean ± SD. (E) The cardiac cells of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups were collected and the levels of [Ca2+]i were measured. Results are expressed as mean ± SD. (F) CaM expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CaM expression is shown in “i”. The CaM expression in DM-8w group is lower than that in Sham group (p<0.01), and the CaM expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CaM expression in Curcumin/P group, Curcumin/ P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). A significant decrease from Sham group is denoted by *p<0.01, a significant increase from DM-8w group is denoted by **p<0.01, and a significant increase from DM-8w group is denoted by ***p<0.01. Abbreviations: CaSR, calcium-sensing receptor; DM, diabetes mellitus; CSE, cystathionine-γ-lyase; CaRS, calcium-sensing receptor stimulator; CaRI, calcium-sensing receptor inhibitor; CaM, calmodulin; P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate); SD, standard deviation.
Figure 7
Figure 7
(A) Histopathologic assessment of myocardial damage; (B) CaSR expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (C) CSE expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (D) H2S level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (E) [Ca2+]i level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (F) CaM expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups. Notes: (A) Light microscope images (×100) in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of histopathological assessment is shown in “i”. The histopathologic damage in DM-8w group is higher than that in Sham group (p<0.01), and the histopathologic damage in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is lower than that in DM-8w group (p<0.01); the histopathologic damage in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly lower than that in DM-8w group (p<0.01). (B) CaSR expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/ P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CaSR expression is shown in “B-i”. The CaSR expression in DM-8w group is lower than that in Sham group (p<0.01), and the CaSR expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CaSR expression in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). (C) CSE expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CSE expression is shown in “C-i”. The CSE expression in DM-8w group is lower than that in Sham group (p<0.01), and the CSE expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CSE expression in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). (D) The blood of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups were collected and the levels of H2S were measured. Results are expressed as mean ± SD. (E) The cardiac cells of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups were collected and the levels of [Ca2+]i were measured. Results are expressed as mean ± SD. (F) CaM expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CaM expression is shown in “i”. The CaM expression in DM-8w group is lower than that in Sham group (p<0.01), and the CaM expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CaM expression in Curcumin/P group, Curcumin/ P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). A significant decrease from Sham group is denoted by *p<0.01, a significant increase from DM-8w group is denoted by **p<0.01, and a significant increase from DM-8w group is denoted by ***p<0.01. Abbreviations: CaSR, calcium-sensing receptor; DM, diabetes mellitus; CSE, cystathionine-γ-lyase; CaRS, calcium-sensing receptor stimulator; CaRI, calcium-sensing receptor inhibitor; CaM, calmodulin; P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate); SD, standard deviation.
Figure 7
Figure 7
(A) Histopathologic assessment of myocardial damage; (B) CaSR expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (C) CSE expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (D) H2S level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (E) [Ca2+]i level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups; (F) CaM expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups. Notes: (A) Light microscope images (×100) in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of histopathological assessment is shown in “i”. The histopathologic damage in DM-8w group is higher than that in Sham group (p<0.01), and the histopathologic damage in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is lower than that in DM-8w group (p<0.01); the histopathologic damage in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly lower than that in DM-8w group (p<0.01). (B) CaSR expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/ P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CaSR expression is shown in “B-i”. The CaSR expression in DM-8w group is lower than that in Sham group (p<0.01), and the CaSR expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CaSR expression in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). (C) CSE expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CSE expression is shown in “C-i”. The CSE expression in DM-8w group is lower than that in Sham group (p<0.01), and the CSE expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CSE expression in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). (D) The blood of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups were collected and the levels of H2S were measured. Results are expressed as mean ± SD. (E) The cardiac cells of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups were collected and the levels of [Ca2+]i were measured. Results are expressed as mean ± SD. (F) CaM expression in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The quantitative analysis of CaM expression is shown in “i”. The CaM expression in DM-8w group is lower than that in Sham group (p<0.01), and the CaM expression in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is higher than that in DM-8w group (p<0.01); the CaM expression in Curcumin/P group, Curcumin/ P+CaRS group, and Curcumin/P+CaRI group is significantly higher than that in DM-8w group (p<0.01). A significant decrease from Sham group is denoted by *p<0.01, a significant increase from DM-8w group is denoted by **p<0.01, and a significant increase from DM-8w group is denoted by ***p<0.01. Abbreviations: CaSR, calcium-sensing receptor; DM, diabetes mellitus; CSE, cystathionine-γ-lyase; CaRS, calcium-sensing receptor stimulator; CaRI, calcium-sensing receptor inhibitor; CaM, calmodulin; P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate); SD, standard deviation.
Figure 8
Figure 8
(A) Histopathologic assessment of myocardial damage; (B) H2S level in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+PAG, Curcumin/P+PAG, Curcumin+ CaRS+PAG, and Curcumin/P+CaRS+PAG groups; (C) CSE expression in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+PAG, Curcumin/P+PAG, Curcumin+CaRS+PAG, and Curcumin/P+CaRS+PAG groups. Notes: (A) Light microscope images (×100) in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+PAG group (e), Curcumin/P+PAG group (f), Curcumin+CaRS+PAG group (g), and Curcumin/P+CaRS+PAG group (h). The quantitative analysis of histopathologic assessment is showed in “i”. The histopathologic damage in DM-8w group is higher than that in Sham group (p<0.01), and the histopathologic damage in Curcumin group, Curcumin+PAG group, and Curcumin+CaRS+PAG group is lower than that in Sham group (p<0.01); the histopathologic damage in Curcumin/P group, Curcumin/P+PAG group, and Curcumin/P+CaRS+PAG group is significantly lower than that in Sham group (p<0.01). (B) The blood of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+PAG, Curcumin/P+PAG, Curcumin+CaRS+PAG, and Curcumin/ P+CaRS+PAG groups were collected and the levels of H2S were measured. Results are expressed as mean ± SD. (C) The cardiac tissues of Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+PAG, Curcumin/P+PAG, Curcumin+CaRS+PAG, and Curcumin/P+CaRS+PAG groups and the expression of CSE were measured. Results are expressed as mean ± SD. A significant decrease from Sham group is denoted by *p<0.01, a significant increase from DM-8w group is denoted by **p<0.01, and a significant increase from DM-8w group is denoted by ***p<0.01. Abbreviations: CaSR, calcium-sensing receptor; DM, diabetes mellitus; CSE, cystathionine-γ-lyase; CaRS, calcium-sensing receptor stimulator; PAG, DL-propargylglycine; CaM, calmodulin; P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate); SD, standard deviation.
Figure 9
Figure 9
(A) Apoptosis assessment of cardiac cells in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+CaRS, Curcumin/P+CaRS, Curcumin+CaRI, and Curcumin/P+CaRI groups. (B) Apoptosis assessment of cardiac cell in Sham, DM-8w, Curcumin, Curcumin/P, Curcumin+PAG, Curcumin/P+PAG, Curcumin+CaRS+PAG, and Curcumin/ P+CaRS+PAG groups. Notes: (A) Apoptosis in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+CaRS group (e), Curcumin/P+CaRS group (f), Curcumin+CaRI group (g), and Curcumin/P+CaRI group (h). The apoptosis in DM-8w group is higher than that in Sham group, and the apoptosis in Curcumin group, Curcumin+CaRS group, and Curcumin+CaRI group is lower than that in DM-8w group; the apoptosis in Curcumin/P group, Curcumin/P+CaRS group, and Curcumin/P+CaRI group is significantly lower than that in DM-8w group. (B) Apoptosis in Sham group (a), DM-8w group (b), Curcumin group (c), Curcumin/P group (d), Curcumin+PAG group (e), Curcumin/P+PAG group (f), Curcumin+CaRS+PAG group (g), and Curcumin/P+CaRS+PAG group (h). The apoptosis in DM-8w group is higher than that in Sham group, and the apoptosis in Curcumin group, Curcumin+PAG group, and Curcumin+CaRS+PAG group is lower than that in DM-8w group; the apoptosis in Curcumin/P group, Curcumin/P+PAG group, and Curcumin/P+CaRS+PAG group is significantly lower than that in DM-8w group. Magnification is ×100. Abbreviations: CaSR, calcium sensing receptor; DM, diabetes mellitus; CaRS, calcium-sensing receptor stimulator; CaRI, calcium-sensing receptor inhibitor; P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate); PAG, DL-propargylglycine.
Scheme 1
Scheme 1
Encapsulation of curcumin by PBLG-PEG-PBLG (P). Abbreviation: P, poly(gamma-benzyl l-glutamate)-poly(ethylene glycol)-poly(gamma-benzyl l-glutamate).
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