Limits...
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

Plasma concentration-time profile of DTX after intravenous administration at a dose of 10 mg/kg of free DTX (□), or DTX-LPH nanoparticles (■).Note: Data shows mean ± SD (n=4).Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard devaition.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4552257&req=5

f7-ijn-10-5249: Plasma concentration-time profile of DTX after intravenous administration at a dose of 10 mg/kg of free DTX (□), or DTX-LPH nanoparticles (■).Note: Data shows mean ± SD (n=4).Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard devaition.

Mentions: As shown in Figure 7 and Table 2, the plasma concentration of DTX was markedly higher for the entirety of the studied period when delivered using LPH than when delivered alone. Free DTX readily disappeared from the blood stream within 6 hours of drug administration. The corresponding pharmacokinetic parameters also revealed the superior systemic performance of DTX-LPH. For instance, DTX-LPH showed 3.4-fold higher AUC0–∞ than free DTX. LPH significantly increased the half-life (t1/2~4.39) of DTX compared with the free drug (t1/2~1.09). The prolonged blood circulation profile of LPH was mainly attributed to the shielding effect of PEG, the excellent stability of the carrier/drug formulation in blood circulation, and the negative surface charge of the nanoparticles.35,36 Additionally, nanosized particles might be able to evade the macrophage system in the systemic blood circulation.


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)

Plasma concentration-time profile of DTX after intravenous administration at a dose of 10 mg/kg of free DTX (□), or DTX-LPH nanoparticles (■).Note: Data shows mean ± SD (n=4).Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard devaition.
© Copyright Policy
Related In: Results  -  Collection

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

f7-ijn-10-5249: Plasma concentration-time profile of DTX after intravenous administration at a dose of 10 mg/kg of free DTX (□), or DTX-LPH nanoparticles (■).Note: Data shows mean ± SD (n=4).Abbreviations: DTX, docetaxel; DTX-LPH, docetaxel-loaded lipid polymer hybrid; SD, standard devaition.
Mentions: As shown in Figure 7 and Table 2, the plasma concentration of DTX was markedly higher for the entirety of the studied period when delivered using LPH than when delivered alone. Free DTX readily disappeared from the blood stream within 6 hours of drug administration. The corresponding pharmacokinetic parameters also revealed the superior systemic performance of DTX-LPH. For instance, DTX-LPH showed 3.4-fold higher AUC0–∞ than free DTX. LPH significantly increased the half-life (t1/2~4.39) of DTX compared with the free drug (t1/2~1.09). The prolonged blood circulation profile of LPH was mainly attributed to the shielding effect of PEG, the excellent stability of the carrier/drug formulation in blood circulation, and the negative surface charge of the nanoparticles.35,36 Additionally, nanosized particles might be able to evade the macrophage system in the systemic blood circulation.

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