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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

The effect of PTX-loaded SLNs modified with HPCD on tumor volume and body weight.Notes: The changes of tumor volumes (A) and body weight (B) according to the administration of saline, PTX solution, or PTX-loaded SLNs modified with HPCD (PSC) (n=3, mean ± SD).Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
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f6-ijn-10-5397: The effect of PTX-loaded SLNs modified with HPCD on tumor volume and body weight.Notes: The changes of tumor volumes (A) and body weight (B) according to the administration of saline, PTX solution, or PTX-loaded SLNs modified with HPCD (PSC) (n=3, mean ± SD).Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Mentions: PTX solution, PSC, and a saline control were separately injected thrice (10 mg/kg each) on days 6, 13, and 20 after tumor inoculations. There were no significant differences in the sizes of tumors until day 23 between PTX solution- and PSC-treated mice (Figure 6A). However, tumor volume was remarkably small, that is, 309.6±18.7 mm3 or 264.5±23.5 mm3, respectively, when treated with PTX solution or PSC after 27 days. In particular, mice treated with PSC had smaller tumor volumes than those treated with PTX solution, indicating greater antitumor efficacy of PSC than that of PTX solution. This is most likely owing to the high cellular uptake and expected sustained release profiles of PTX from PSC within the tumor tissue based on the apoptosis results.


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)

The effect of PTX-loaded SLNs modified with HPCD on tumor volume and body weight.Notes: The changes of tumor volumes (A) and body weight (B) according to the administration of saline, PTX solution, or PTX-loaded SLNs modified with HPCD (PSC) (n=3, mean ± SD).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

f6-ijn-10-5397: The effect of PTX-loaded SLNs modified with HPCD on tumor volume and body weight.Notes: The changes of tumor volumes (A) and body weight (B) according to the administration of saline, PTX solution, or PTX-loaded SLNs modified with HPCD (PSC) (n=3, mean ± SD).Abbreviations: PTX, Paclitaxel; SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
Mentions: PTX solution, PSC, and a saline control were separately injected thrice (10 mg/kg each) on days 6, 13, and 20 after tumor inoculations. There were no significant differences in the sizes of tumors until day 23 between PTX solution- and PSC-treated mice (Figure 6A). However, tumor volume was remarkably small, that is, 309.6±18.7 mm3 or 264.5±23.5 mm3, respectively, when treated with PTX solution or PSC after 27 days. In particular, mice treated with PSC had smaller tumor volumes than those treated with PTX solution, indicating greater antitumor efficacy of PSC than that of PTX solution. This is most likely owing to the high cellular uptake and expected sustained release profiles of PTX from PSC within the tumor tissue based on the apoptosis results.

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