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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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Morphology and particle size distribution of PNPC. (a) Red line shows average results of freshly prepared PNPC samples (0–25% curcumin encapsulation in PNP). It shows three particle sizes, 18.3 ± 5.3, 65.5 ± 30, and 283 ± 112 nm. Green line shows average results of PNPC samples after one week at 25°C (0–25% curcumin encapsulation in PNP). It shows one particle size of 99.4 ± 42.6 nm. Blue line shows average result of all samples with two sizes, 18.3 ± 5.3 (they seem to be micelles) and 99.4 ± 65 nm (they seem to be polymersomes). (b) Atomic force microscopy (AFM) results. AFM image of redissolved PNPC after freeze-drying (0.05 mg/mL) also showed two particle forms and sizes. Smaller particles (<40 nm) seem to be micelles and larger particles (>40 nm) seem to be polymersomes.
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fig2: Morphology and particle size distribution of PNPC. (a) Red line shows average results of freshly prepared PNPC samples (0–25% curcumin encapsulation in PNP). It shows three particle sizes, 18.3 ± 5.3, 65.5 ± 30, and 283 ± 112 nm. Green line shows average results of PNPC samples after one week at 25°C (0–25% curcumin encapsulation in PNP). It shows one particle size of 99.4 ± 42.6 nm. Blue line shows average result of all samples with two sizes, 18.3 ± 5.3 (they seem to be micelles) and 99.4 ± 65 nm (they seem to be polymersomes). (b) Atomic force microscopy (AFM) results. AFM image of redissolved PNPC after freeze-drying (0.05 mg/mL) also showed two particle forms and sizes. Smaller particles (<40 nm) seem to be micelles and larger particles (>40 nm) seem to be polymersomes.

Mentions: The size, morphology, and polydispersity of the nanoparticles were evaluated using dynamic light-scattering technique (DLS) and AFM methods (Figure 2). The results show that two forms of particles were produced in the process of synthesis, micelles and polymersomes with the average size of 18.33 ± 5.32 nm and 99.44 ± 65 nm, respectively. The freshly prepared PNP with different curcumin content (0–25%) were monodisperse (PdI = 0.332 ± 0.13), with three particle forms 53.5% micelles (18.33 ± 5.3 nm), 38.8% polymersomes (65.5 ± 30 nm), and 7.5% polymersomes (283.6 ± 112 nm). However, after one week of incubation at 25°C, the particle forms changed to be more monodisperse (PdI = 0.182 ± 0.072) with 100% polymersomes (99.44 ± 42.56 nm). The results of AFM analysis show that the shape of PNPC was in accordance with DLS analysis (Figure 2(b)). However, compared to DLS analysis, the AFM results show the larger size of PNPC which can be attributed to the expansion of spherical micelles or vesicles (polymersomes) in mica surface after drying its solution. Moreover, the AFM results show that in PNPC graph the z-dimensional (height) bar is smaller than X- and Y-dimensional bars which support this claim (Supplemental Figure  4). The PNPC is indeed stable in the presence of oleate in this nanoformulation. The negative zeta-potential was found to be −29.3 ± 5.2 mV at concentration of 0.05 mg/mL (slightly higher concentration than CMC point; 0.03 mg/mL). This low zeta-potential is at optimum range for stability of PNPC and explains the reason of developing more uniform size distribution (PdI = 0.182 ± 0.072) after one week at room temperature [25, 26].


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)

Morphology and particle size distribution of PNPC. (a) Red line shows average results of freshly prepared PNPC samples (0–25% curcumin encapsulation in PNP). It shows three particle sizes, 18.3 ± 5.3, 65.5 ± 30, and 283 ± 112 nm. Green line shows average results of PNPC samples after one week at 25°C (0–25% curcumin encapsulation in PNP). It shows one particle size of 99.4 ± 42.6 nm. Blue line shows average result of all samples with two sizes, 18.3 ± 5.3 (they seem to be micelles) and 99.4 ± 65 nm (they seem to be polymersomes). (b) Atomic force microscopy (AFM) results. AFM image of redissolved PNPC after freeze-drying (0.05 mg/mL) also showed two particle forms and sizes. Smaller particles (<40 nm) seem to be micelles and larger particles (>40 nm) seem to be polymersomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Morphology and particle size distribution of PNPC. (a) Red line shows average results of freshly prepared PNPC samples (0–25% curcumin encapsulation in PNP). It shows three particle sizes, 18.3 ± 5.3, 65.5 ± 30, and 283 ± 112 nm. Green line shows average results of PNPC samples after one week at 25°C (0–25% curcumin encapsulation in PNP). It shows one particle size of 99.4 ± 42.6 nm. Blue line shows average result of all samples with two sizes, 18.3 ± 5.3 (they seem to be micelles) and 99.4 ± 65 nm (they seem to be polymersomes). (b) Atomic force microscopy (AFM) results. AFM image of redissolved PNPC after freeze-drying (0.05 mg/mL) also showed two particle forms and sizes. Smaller particles (<40 nm) seem to be micelles and larger particles (>40 nm) seem to be polymersomes.
Mentions: The size, morphology, and polydispersity of the nanoparticles were evaluated using dynamic light-scattering technique (DLS) and AFM methods (Figure 2). The results show that two forms of particles were produced in the process of synthesis, micelles and polymersomes with the average size of 18.33 ± 5.32 nm and 99.44 ± 65 nm, respectively. The freshly prepared PNP with different curcumin content (0–25%) were monodisperse (PdI = 0.332 ± 0.13), with three particle forms 53.5% micelles (18.33 ± 5.3 nm), 38.8% polymersomes (65.5 ± 30 nm), and 7.5% polymersomes (283.6 ± 112 nm). However, after one week of incubation at 25°C, the particle forms changed to be more monodisperse (PdI = 0.182 ± 0.072) with 100% polymersomes (99.44 ± 42.56 nm). The results of AFM analysis show that the shape of PNPC was in accordance with DLS analysis (Figure 2(b)). However, compared to DLS analysis, the AFM results show the larger size of PNPC which can be attributed to the expansion of spherical micelles or vesicles (polymersomes) in mica surface after drying its solution. Moreover, the AFM results show that in PNPC graph the z-dimensional (height) bar is smaller than X- and Y-dimensional bars which support this claim (Supplemental Figure  4). The PNPC is indeed stable in the presence of oleate in this nanoformulation. The negative zeta-potential was found to be −29.3 ± 5.2 mV at concentration of 0.05 mg/mL (slightly higher concentration than CMC point; 0.03 mg/mL). This low zeta-potential is at optimum range for stability of PNPC and explains the reason of developing more uniform size distribution (PdI = 0.182 ± 0.072) after one week at room temperature [25, 26].

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