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Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells.

Tran TH, Ramasamy T, Choi JY, Nguyen HT, Pham TT, Jeong JH, Ku SK, Choi HG, Yong CS, Kim JO - Int J Nanomedicine (2015)

Bottom Line: The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX.The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice.The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.

ABSTRACT
The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.

No MeSH data available.


Related in: MedlinePlus

Physical properties of DTX-LPH nanoparticles.Notes: (A) Transmission electron micrograph, (B) atomic force micrograph, (C) X-ray diffraction patterns, and (D) in vitro drug release (data are expressed as mean ± SD, n=3).Abbreviations: DTX, docetaxel; LPH, lipid polymer hybrid; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard deviation.
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f2-ijn-10-5249: Physical properties of DTX-LPH nanoparticles.Notes: (A) Transmission electron micrograph, (B) atomic force micrograph, (C) X-ray diffraction patterns, and (D) in vitro drug release (data are expressed as mean ± SD, n=3).Abbreviations: DTX, docetaxel; LPH, lipid polymer hybrid; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard deviation.

Mentions: The morphology of DTX-LPH is shown in Figure 2A and B. Transmission electron microscopy images revealed a nanosized, spherical-shaped, compact core-shell structure with a size consistent with the DLS data. A similar result was observed using atomic force microscopy, which also provided the 3D shape of the nanoparticles. X-ray diffraction analysis was performed to evaluate the physical status of drug and formulation (Figure 2C). The diffractogram for free DTX showed numerous sharp, intense peaks reflecting its high crystallinity. The lack of a characteristic peak in blank LPH and DTX-LPH indicates that the drug is in the amorphous form or molecularly dispersed after encapsulation.10


Tumor-targeting, pH-sensitive nanoparticles for docetaxel delivery to drug-resistant cancer cells.

Tran TH, Ramasamy T, Choi JY, Nguyen HT, Pham TT, Jeong JH, Ku SK, Choi HG, Yong CS, Kim JO - Int J Nanomedicine (2015)

Physical properties of DTX-LPH nanoparticles.Notes: (A) Transmission electron micrograph, (B) atomic force micrograph, (C) X-ray diffraction patterns, and (D) in vitro drug release (data are expressed as mean ± SD, n=3).Abbreviations: DTX, docetaxel; LPH, lipid polymer hybrid; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard deviation.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4552257&req=5

f2-ijn-10-5249: Physical properties of DTX-LPH nanoparticles.Notes: (A) Transmission electron micrograph, (B) atomic force micrograph, (C) X-ray diffraction patterns, and (D) in vitro drug release (data are expressed as mean ± SD, n=3).Abbreviations: DTX, docetaxel; LPH, lipid polymer hybrid; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard deviation.
Mentions: The morphology of DTX-LPH is shown in Figure 2A and B. Transmission electron microscopy images revealed a nanosized, spherical-shaped, compact core-shell structure with a size consistent with the DLS data. A similar result was observed using atomic force microscopy, which also provided the 3D shape of the nanoparticles. X-ray diffraction analysis was performed to evaluate the physical status of drug and formulation (Figure 2C). The diffractogram for free DTX showed numerous sharp, intense peaks reflecting its high crystallinity. The lack of a characteristic peak in blank LPH and DTX-LPH indicates that the drug is in the amorphous form or molecularly dispersed after encapsulation.10

Bottom Line: The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX.The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice.The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Yeungnam University, Dae-Dong, South Korea.

ABSTRACT
The attachment of polyethylene glycol (PEG) increases the circulation time of drug-containing nanoparticles; however, this also negatively affects cellular uptake. To overcome this problem, unique lipid polymer hybrid (LPH) nanoparticles were developed with a pH-responsive PEG layer that detached prior to cell uptake. Docetaxel (DTX) was incorporated into the lipid core of the nanoparticles, which was then shielded with the pH-responsive block co-polymer polyethylene glycol-b-polyaspartic acid (PEG-b-PAsp) using a modified emulsion method. The optimized LPH nanoparticles were ~200 nm and had a narrow size distribution. Drug release from DTX-loaded LPH (DTX-LPH) nanoparticles was pH-sensitive, which is beneficial for tumor targeting. More importantly, DTX-LPH nanoparticles were able to effectively induce apoptosis in cancer cells. The negative surface charge and PEG shell of vehicle remarkably enhanced the blood circulation and physiological activity of DTX-LPH nanoparticles compared with that of free DTX. The nanoparticles were also found to reduce the size of tumors in tumor-bearing xenograft mice. The in vivo anticancer effect of DTX-LPH nanoparticles was further confirmed by the elevated levels of caspase-3 and poly ADP ribose polymerase found in the tumors after treatment. Thus, the results suggest that this novel LPH system could be an effective new treatment for cancer.

No MeSH data available.


Related in: MedlinePlus