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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

Cell proliferation of PTX-loaded SLNs (A) and PTX-loaded SLNs modified with HPCD (B) at 5 µM or 10 µM PTX concentration for 24 hours, 48 hours, or 72 hours incubation by MTT assay (n=3, mean ± SD). *P<0.05; **P<0.01.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
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f1-ijn-10-5397: Cell proliferation of PTX-loaded SLNs (A) and PTX-loaded SLNs modified with HPCD (B) at 5 µM or 10 µM PTX concentration for 24 hours, 48 hours, or 72 hours incubation by MTT assay (n=3, mean ± SD). *P<0.05; **P<0.01.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Mentions: The antiproliferation efficiency of PS or PSC was investigated in MCF-7 cells. Incubation of MCF-7 cells for 24 hours, 48 hours, or 72 hours with PSC containing PTX at concentrations up to 10 µM efficiently inhibited proliferation. Both PS and PSC exhibited concentration- and time-dependent inhibitory effects (Figure 1). As a reference, the viability of Caco-2 cells treated with PTX solution for 72 hours was 71.45.19 The inhibition efficiency of PS and PSC containing 5 µM and 10 µM PTX increased upon increasing the incubation time from 24 hours to 48 hours. The cell viability after treatment with PSC significantly decreased upon increasing the incubation time up to 72 hours at both PTX concentrations. These results indicated that PSC exhibited a sustained and prolonged cytotoxic effect in MCF-7 cells.


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)

Cell proliferation of PTX-loaded SLNs (A) and PTX-loaded SLNs modified with HPCD (B) at 5 µM or 10 µM PTX concentration for 24 hours, 48 hours, or 72 hours incubation by MTT assay (n=3, mean ± SD). *P<0.05; **P<0.01.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

f1-ijn-10-5397: Cell proliferation of PTX-loaded SLNs (A) and PTX-loaded SLNs modified with HPCD (B) at 5 µM or 10 µM PTX concentration for 24 hours, 48 hours, or 72 hours incubation by MTT assay (n=3, mean ± SD). *P<0.05; **P<0.01.Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
Mentions: The antiproliferation efficiency of PS or PSC was investigated in MCF-7 cells. Incubation of MCF-7 cells for 24 hours, 48 hours, or 72 hours with PSC containing PTX at concentrations up to 10 µM efficiently inhibited proliferation. Both PS and PSC exhibited concentration- and time-dependent inhibitory effects (Figure 1). As a reference, the viability of Caco-2 cells treated with PTX solution for 72 hours was 71.45.19 The inhibition efficiency of PS and PSC containing 5 µM and 10 µM PTX increased upon increasing the incubation time from 24 hours to 48 hours. The cell viability after treatment with PSC significantly decreased upon increasing the incubation time up to 72 hours at both PTX concentrations. These results indicated that PSC exhibited a sustained and prolonged cytotoxic effect in MCF-7 cells.

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