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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

Cellular uptake into MCF-7 cells treated with Nile red solution, Nile red-loaded SLNs, or Nile red-loaded SLNs modified with HPCD for 2 hours or 8 hours of incubation.Notes: (A) Nile red solution for 2 hours, (B) Nile red solution for 8 hours, (C) Nile red-loaded SLNs for 2 hours, (D) Nile red-loaded SLNs for 8 hours, (E) Nile red-loaded SLNs modified with HPCD for 2 hours, (F) Nile red-loaded SLNs modified with HPCD for 8 hours.Abbreviations: SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
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f2-ijn-10-5397: Cellular uptake into MCF-7 cells treated with Nile red solution, Nile red-loaded SLNs, or Nile red-loaded SLNs modified with HPCD for 2 hours or 8 hours of incubation.Notes: (A) Nile red solution for 2 hours, (B) Nile red solution for 8 hours, (C) Nile red-loaded SLNs for 2 hours, (D) Nile red-loaded SLNs for 8 hours, (E) Nile red-loaded SLNs modified with HPCD for 2 hours, (F) Nile red-loaded SLNs modified with HPCD for 8 hours.Abbreviations: SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.

Mentions: To observe cellular uptake by confocal microscopy, MCF-7 cells were treated with Nile red solution, NS, or NSC (Figure 2). NS and NSC exhibited more fluorescence than Nile red solution at all incubation times. Furthermore, NSC showed the highest fluorescence among the tested formulations. The enhanced uptake of Nile red from NSC might be owing to the increased solubility of Nile red by HPCD in the cell membranes. Yamazaki and Ito reported that high-solubility materials such as PEG can facilitate the cellular uptake of nanoparticles.21 Furthermore, particle size and shape were previously reported to significantly affect cellular uptake.22 Our previous study reported that the particle size of PSC was 251.4±12.0 nm. Therefore, the small PSC particle size might improve the rate and amount of cellular uptake.19 Because NSC was prepared using the same method as that of PSC, the high fluorescence observed for NSC is consistent with the results obtained previously.


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)

Cellular uptake into MCF-7 cells treated with Nile red solution, Nile red-loaded SLNs, or Nile red-loaded SLNs modified with HPCD for 2 hours or 8 hours of incubation.Notes: (A) Nile red solution for 2 hours, (B) Nile red solution for 8 hours, (C) Nile red-loaded SLNs for 2 hours, (D) Nile red-loaded SLNs for 8 hours, (E) Nile red-loaded SLNs modified with HPCD for 2 hours, (F) Nile red-loaded SLNs modified with HPCD for 8 hours.Abbreviations: 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

f2-ijn-10-5397: Cellular uptake into MCF-7 cells treated with Nile red solution, Nile red-loaded SLNs, or Nile red-loaded SLNs modified with HPCD for 2 hours or 8 hours of incubation.Notes: (A) Nile red solution for 2 hours, (B) Nile red solution for 8 hours, (C) Nile red-loaded SLNs for 2 hours, (D) Nile red-loaded SLNs for 8 hours, (E) Nile red-loaded SLNs modified with HPCD for 2 hours, (F) Nile red-loaded SLNs modified with HPCD for 8 hours.Abbreviations: SLNs, solid lipid nanoparticles; HPCD, 2-hydroxypropyl-β-cyclodextrin.
Mentions: To observe cellular uptake by confocal microscopy, MCF-7 cells were treated with Nile red solution, NS, or NSC (Figure 2). NS and NSC exhibited more fluorescence than Nile red solution at all incubation times. Furthermore, NSC showed the highest fluorescence among the tested formulations. The enhanced uptake of Nile red from NSC might be owing to the increased solubility of Nile red by HPCD in the cell membranes. Yamazaki and Ito reported that high-solubility materials such as PEG can facilitate the cellular uptake of nanoparticles.21 Furthermore, particle size and shape were previously reported to significantly affect cellular uptake.22 Our previous study reported that the particle size of PSC was 251.4±12.0 nm. Therefore, the small PSC particle size might improve the rate and amount of cellular uptake.19 Because NSC was prepared using the same method as that of PSC, the high fluorescence observed for NSC is consistent with the results obtained previously.

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