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Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

Alizadeh AM, Sadeghizadeh M, Najafi F, Ardestani SK, Erfani-Moghadam V, Khaniki M, Rezaei A, Zamani M, Khodayari S, Khodayari H, Mohagheghi MA - Biomed Res Int (2015)

Bottom Line: In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05).These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models.Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran 14197-33141, Iran.

ABSTRACT
Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

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Related in: MedlinePlus

Light microscopic analysis of organs impressed from PNPC (125 mg/kg). Mild Kupffer cells hyperplasia and sinusoidal distention in favor of congestion were seen in the liver tissue [(A) (20x), (a) (40x)]. Moderate congestion, sinusoidal dilatation with preserved white lymphoid pulp was seen in the spleen tissue [(B) (20x), (b) (20x)]. The glomeruli were unremarkable but mild peritubular congestion and proteinaceous cast formations were noted in some kidney tubules [(C) (20x), (c) (40x)].
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fig6: Light microscopic analysis of organs impressed from PNPC (125 mg/kg). Mild Kupffer cells hyperplasia and sinusoidal distention in favor of congestion were seen in the liver tissue [(A) (20x), (a) (40x)]. Moderate congestion, sinusoidal dilatation with preserved white lymphoid pulp was seen in the spleen tissue [(B) (20x), (b) (20x)]. The glomeruli were unremarkable but mild peritubular congestion and proteinaceous cast formations were noted in some kidney tubules [(C) (20x), (c) (40x)].

Mentions: In order to obtain an accurate diagnosis of PNPC and PNP toxicity on microscopic levels, major organs were histopathologically evaluated. Compared with control, animals treated with 125 mg/kg PNPC and PNP developed slight abdominal ascites, kidney, liver, and spleen congestion after one-week consecutive injections. AST, ALT, ALP, and GGT drastic increases in these groups may be assumed as liver dysfunction. These changes were also congruent with elevated renal biomarkers. In the liver, mild Kupffer cells hyperplasia and sinusoidal distention in favor of congestion were seen (Figure 6(A)). In addition, we observed moderate congestion, sinusoidal dilatation with preserved white lymphoid pulp in the spleen tissue (Figure 6(B)). In the kidney, the glomeruli were unremarkable but mild peritubular congestion and proteinaceous cast formations were noted in some tubules (Figure 6(C)). In all of the histopathological examinations we observed minimal hepatic and renal toxicity. No histological abnormality was found in other major organs such as the brain, the heart, and the lung. Additionally, no significant pathologic changes were found in the major organs of animals treated with 31.25 mg/kg PNPC and lower doses compared with the control group, so 31.25 mg/kg dose was ruled out as the toxic dose.


Encapsulation of curcumin in diblock copolymer micelles for cancer therapy.

Alizadeh AM, Sadeghizadeh M, Najafi F, Ardestani SK, Erfani-Moghadam V, Khaniki M, Rezaei A, Zamani M, Khodayari S, Khodayari H, Mohagheghi MA - Biomed Res Int (2015)

Light microscopic analysis of organs impressed from PNPC (125 mg/kg). Mild Kupffer cells hyperplasia and sinusoidal distention in favor of congestion were seen in the liver tissue [(A) (20x), (a) (40x)]. Moderate congestion, sinusoidal dilatation with preserved white lymphoid pulp was seen in the spleen tissue [(B) (20x), (b) (20x)]. The glomeruli were unremarkable but mild peritubular congestion and proteinaceous cast formations were noted in some kidney tubules [(C) (20x), (c) (40x)].
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4352453&req=5

fig6: Light microscopic analysis of organs impressed from PNPC (125 mg/kg). Mild Kupffer cells hyperplasia and sinusoidal distention in favor of congestion were seen in the liver tissue [(A) (20x), (a) (40x)]. Moderate congestion, sinusoidal dilatation with preserved white lymphoid pulp was seen in the spleen tissue [(B) (20x), (b) (20x)]. The glomeruli were unremarkable but mild peritubular congestion and proteinaceous cast formations were noted in some kidney tubules [(C) (20x), (c) (40x)].
Mentions: In order to obtain an accurate diagnosis of PNPC and PNP toxicity on microscopic levels, major organs were histopathologically evaluated. Compared with control, animals treated with 125 mg/kg PNPC and PNP developed slight abdominal ascites, kidney, liver, and spleen congestion after one-week consecutive injections. AST, ALT, ALP, and GGT drastic increases in these groups may be assumed as liver dysfunction. These changes were also congruent with elevated renal biomarkers. In the liver, mild Kupffer cells hyperplasia and sinusoidal distention in favor of congestion were seen (Figure 6(A)). In addition, we observed moderate congestion, sinusoidal dilatation with preserved white lymphoid pulp in the spleen tissue (Figure 6(B)). In the kidney, the glomeruli were unremarkable but mild peritubular congestion and proteinaceous cast formations were noted in some tubules (Figure 6(C)). In all of the histopathological examinations we observed minimal hepatic and renal toxicity. No histological abnormality was found in other major organs such as the brain, the heart, and the lung. Additionally, no significant pathologic changes were found in the major organs of animals treated with 31.25 mg/kg PNPC and lower doses compared with the control group, so 31.25 mg/kg dose was ruled out as the toxic dose.

Bottom Line: In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05).These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models.Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Center, Tehran University of Medical Sciences, Tehran 14197-33141, Iran.

ABSTRACT
Application of nanoparticles has recently promising results for water insoluble agents like curcumin. In this study, we synthesized polymeric nanoparticle-curcumin (PNPC) and then showed its efficiency, drug loading, stability, and safety. Therapeutic effects of PNPC were also assessed on two cell lines and in an animal model of breast cancer. PNPC remarkably suppressed mammary and hepatocellular carcinoma cells proliferation (P < 0.05). Under the dosing procedure, PNPC was safe at 31.25 mg/kg and lower doses. Higher doses demonstrated minimal hepatocellular and renal toxicity in paraclinical and histopathological examinations. Tumor take rate in PNPC-treated group was 37.5% compared with 87.5% in control (P < 0.05). Average tumor size and weight were significantly lower in PNPC group than control (P < 0.05). PNPC increased proapoptotic Bax protein expression (P < 0.05). Antiapoptotic Bcl-2 protein expression, however, was lower in PNPC-treated animals than the control ones (P < 0.05). In addition, proliferative and angiogenic parameters were statistically decreased in PNPC-treated animals (P < 0.05). These results highlight the suppressing role for PNPC in in vitro and in vivo tumor growth models. Our findings provide credible evidence for superior biocompatibility of the polymeric nanocarrier in pharmacological arena together with an excellent tumor-suppressing response.

Show MeSH
Related in: MedlinePlus