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Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-β-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection.

Baek JS, Kim JH, Park JS, Cho CW - Int J Nanomedicine (2015)

Bottom Line: PSC were successfully prepared by hot-melted sonication and had smaller diameters than PS.PSC exhibited improved anticancer activity and cellular uptake in MCF-7 cells.Based on these results, PSC could be considered as a potential therapeutic PTX delivery system for breast cancer with low renal toxicity.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea.

ABSTRACT

Background: Paclitaxel (PTX) solid lipid nanoparticles (SLNs) modified with 2-hydroxypropyl-β-cyclodextrin (HPCD) were evaluated for their ability to enhance PTX absorption and reduce the nephrotoxicity accompanying intravenous administration.

Methods: PTX-loaded SLNs (PS) and PTX-loaded SLNs modified using HPCD (PSC) were prepared by hot-melted sonication. The anticancer activity of PSC was evaluated in MCF-7 cells, and confocal microscopy was used to quantify the cellular uptake. The pharmacokinetic profiles of PTX released from PSC after intravenous administration were studied in rats. Furthermore, kidney toxicity was determined by measuring the kidney size and plasma creatinine level.

Results: PSC were successfully prepared by hot-melted sonication and had smaller diameters than PS. PSC exhibited improved anticancer activity and cellular uptake in MCF-7 cells. Furthermore, PSC showed higher bioavailability in rats after intravenous administration than PTX solution; however, no significant differences in kidney toxicity were observed.

Conclusion: Based on these results, PSC could be considered as a potential therapeutic PTX delivery system for breast cancer with low renal toxicity.

No MeSH data available.


Related in: MedlinePlus

Apoptotic assay in MCF-7 cells treated with PTX solution, PTX-loaded SLNs, or PTX-loaded SLNs modified with HPCD corresponding 10 µM of PTX for 2 hours or 8 hours of incubation.Notes: (A) PTX solution for 2 hours, (B) PTX solution for 8 hours, (C) PTX-loaded SLNs for 2 hours; (D) PTX-loaded SLNs for 8 hours, (E) PTX-loaded SLNs modified with HPCD for 2 hours, (F) PTX-loaded SLNs modified with HPCD for 8 hours.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
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f3-ijn-10-5397: Apoptotic assay in MCF-7 cells treated with PTX solution, PTX-loaded SLNs, or PTX-loaded SLNs modified with HPCD corresponding 10 µM of PTX for 2 hours or 8 hours of incubation.Notes: (A) PTX solution for 2 hours, (B) PTX solution for 8 hours, (C) PTX-loaded SLNs for 2 hours; (D) PTX-loaded SLNs for 8 hours, (E) PTX-loaded SLNs modified with HPCD for 2 hours, (F) PTX-loaded SLNs modified with HPCD for 8 hours.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Mentions: Apoptotic effect of PTX was examined by staining PTX solution-, PS-, or PSC-treated MCF-7 cells with annexin V-FITC/PI (Figure 3). Apoptosis or programed cell death occurring after efficient cell damage plays an important role in the development and health of multicellular organisms. Dysregulation of apoptosis can disrupt the balance between cell growth and cell death and is thus an important step in cancer development.23 Evasion of apoptosis has been considered a hallmark of cancer.24 Treatment with PS or PSC for 8 hours dramatically increased the population of annexin V-positive cells to 26.0% or 44.5%, respectively, indicating the occurrence of late apoptosis in MCF-7 cells. Furthermore, PS and PSC increased the population of PI-positive cells to 17.0% and 20.9%, respectively. Notably, compared with PTX solution or PS, PSC exhibited 44.5% apoptotic cell death and 20.9% necrotic cell death because apoptosis and necrosis were more sustained at increased incubation time. Based on these results, we hypothesized that HPCD enhanced PTX-induced apoptosis in PSC, which is consistent with the cell proliferation data.


Modification of paclitaxel-loaded solid lipid nanoparticles with 2-hydroxypropyl-β-cyclodextrin enhances absorption and reduces nephrotoxicity associated with intravenous injection.

Baek JS, Kim JH, Park JS, Cho CW - Int J Nanomedicine (2015)

Apoptotic assay in MCF-7 cells treated with PTX solution, PTX-loaded SLNs, or PTX-loaded SLNs modified with HPCD corresponding 10 µM of PTX for 2 hours or 8 hours of incubation.Notes: (A) PTX solution for 2 hours, (B) PTX solution for 8 hours, (C) PTX-loaded SLNs for 2 hours; (D) PTX-loaded SLNs for 8 hours, (E) PTX-loaded SLNs modified with HPCD for 2 hours, (F) PTX-loaded SLNs modified with HPCD for 8 hours.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4554395&req=5

f3-ijn-10-5397: Apoptotic assay in MCF-7 cells treated with PTX solution, PTX-loaded SLNs, or PTX-loaded SLNs modified with HPCD corresponding 10 µM of PTX for 2 hours or 8 hours of incubation.Notes: (A) PTX solution for 2 hours, (B) PTX solution for 8 hours, (C) PTX-loaded SLNs for 2 hours; (D) PTX-loaded SLNs for 8 hours, (E) PTX-loaded SLNs modified with HPCD for 2 hours, (F) PTX-loaded SLNs modified with HPCD for 8 hours.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
Mentions: Apoptotic effect of PTX was examined by staining PTX solution-, PS-, or PSC-treated MCF-7 cells with annexin V-FITC/PI (Figure 3). Apoptosis or programed cell death occurring after efficient cell damage plays an important role in the development and health of multicellular organisms. Dysregulation of apoptosis can disrupt the balance between cell growth and cell death and is thus an important step in cancer development.23 Evasion of apoptosis has been considered a hallmark of cancer.24 Treatment with PS or PSC for 8 hours dramatically increased the population of annexin V-positive cells to 26.0% or 44.5%, respectively, indicating the occurrence of late apoptosis in MCF-7 cells. Furthermore, PS and PSC increased the population of PI-positive cells to 17.0% and 20.9%, respectively. Notably, compared with PTX solution or PS, PSC exhibited 44.5% apoptotic cell death and 20.9% necrotic cell death because apoptosis and necrosis were more sustained at increased incubation time. Based on these results, we hypothesized that HPCD enhanced PTX-induced apoptosis in PSC, which is consistent with the cell proliferation data.

Bottom Line: PSC were successfully prepared by hot-melted sonication and had smaller diameters than PS.PSC exhibited improved anticancer activity and cellular uptake in MCF-7 cells.Based on these results, PSC could be considered as a potential therapeutic PTX delivery system for breast cancer with low renal toxicity.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy and Institute of Drug Research and Development, Chungnam National University, Daejeon, South Korea.

ABSTRACT

Background: Paclitaxel (PTX) solid lipid nanoparticles (SLNs) modified with 2-hydroxypropyl-β-cyclodextrin (HPCD) were evaluated for their ability to enhance PTX absorption and reduce the nephrotoxicity accompanying intravenous administration.

Methods: PTX-loaded SLNs (PS) and PTX-loaded SLNs modified using HPCD (PSC) were prepared by hot-melted sonication. The anticancer activity of PSC was evaluated in MCF-7 cells, and confocal microscopy was used to quantify the cellular uptake. The pharmacokinetic profiles of PTX released from PSC after intravenous administration were studied in rats. Furthermore, kidney toxicity was determined by measuring the kidney size and plasma creatinine level.

Results: PSC were successfully prepared by hot-melted sonication and had smaller diameters than PS. PSC exhibited improved anticancer activity and cellular uptake in MCF-7 cells. Furthermore, PSC showed higher bioavailability in rats after intravenous administration than PTX solution; however, no significant differences in kidney toxicity were observed.

Conclusion: Based on these results, PSC could be considered as a potential therapeutic PTX delivery system for breast cancer with low renal toxicity.

No MeSH data available.


Related in: MedlinePlus