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Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.

Wang B, Lv L, Wang Z, Jiang Y, Lv W, Liu X, Wang Z, Zhao Y, Xin H, Xu Q - Sci Rep (2015)

Bottom Line: The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively.The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation.Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.

No MeSH data available.


Related in: MedlinePlus

Change in body weight of animals as a function of time in healthy ICR mice.Mice were injected i.v. administration with 100 mg/kg blank Pep-NP or negative control (Saline) for 6 days, one dose per day (n = 5).
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f9: Change in body weight of animals as a function of time in healthy ICR mice.Mice were injected i.v. administration with 100 mg/kg blank Pep-NP or negative control (Saline) for 6 days, one dose per day (n = 5).

Mentions: The systemic toxicity of blank Pep-NP was evaluated in healthy mice. Compared with the saline group, no deaths and obvious body weight loss were observed in all test groups during the study period (Fig. 9). The tissue sections of heart, liver, spleen, lung, kidney and brain stained with H&E showed no any apparent change in cellular structure and no necrosis, congestion or hydropic degeneration was observed compared with the saline group (Fig. 10). Moreover, there was no significant difference about the serum aspartate transaminase (AST), alanine transaminase (ALT), urea nitrogen (BUN) and creatinine levels between Pep-NP and saline group (Table 4), indicating that no inflammatory reactions occurred in these tissues. Taken together, our results exhibited that intravenous successive administration of 100 mg/kg Pep-NP for 6 days did not cause systemic toxicity.


Improved anti-glioblastoma efficacy by IL-13Rα2 mediated copolymer nanoparticles loaded with paclitaxel.

Wang B, Lv L, Wang Z, Jiang Y, Lv W, Liu X, Wang Z, Zhao Y, Xin H, Xu Q - Sci Rep (2015)

Change in body weight of animals as a function of time in healthy ICR mice.Mice were injected i.v. administration with 100 mg/kg blank Pep-NP or negative control (Saline) for 6 days, one dose per day (n = 5).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4645113&req=5

f9: Change in body weight of animals as a function of time in healthy ICR mice.Mice were injected i.v. administration with 100 mg/kg blank Pep-NP or negative control (Saline) for 6 days, one dose per day (n = 5).
Mentions: The systemic toxicity of blank Pep-NP was evaluated in healthy mice. Compared with the saline group, no deaths and obvious body weight loss were observed in all test groups during the study period (Fig. 9). The tissue sections of heart, liver, spleen, lung, kidney and brain stained with H&E showed no any apparent change in cellular structure and no necrosis, congestion or hydropic degeneration was observed compared with the saline group (Fig. 10). Moreover, there was no significant difference about the serum aspartate transaminase (AST), alanine transaminase (ALT), urea nitrogen (BUN) and creatinine levels between Pep-NP and saline group (Table 4), indicating that no inflammatory reactions occurred in these tissues. Taken together, our results exhibited that intravenous successive administration of 100 mg/kg Pep-NP for 6 days did not cause systemic toxicity.

Bottom Line: The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively.The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation.Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days).

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmacy, Nanjing Medical University, Nanjing 211166, China.

ABSTRACT
Glioma presents one of the most malignant brain tumors, and the therapeutic effect is often limited due to the existence of brain tumor barrier. Based on interleukin-13 receptor α2 (IL-13Rα2) over-expression on glioma cell, it was demonstrated to be a potential receptor for glioma targeting. In this study, Pep-1-conjugated PEGylated nanoparticles loaded with paclitaxel (Pep-NP-PTX) were developed as a targeting drug delivery system for glioma treatment. The Pep-NP-PTX presented satisfactory size of 95.78 nm with narrow size distribution. Compared with NP-PTX, Pep-NP-PTX exhibited significantly enhanced cellular uptake in C6 cells (p < 0.001). The in vitro anti-proliferation evaluation showed that the IC50 were 146 ng/ml and 349 ng/ml of Pep-NP-PTX and NP-PTX, respectively. The in vivo fluorescent image results indicated that Pep-NP had higher specificity and efficiency in intracranial tumor accumulation. Following intravenous administration, Pep-NP-PTX could enhance the distribution of PTX in vivo glioma section, 1.98, 1.91 and 1.53-fold over that of NP-PTX group after 0.5, 1 and 4 h, respectively. Pep-NP-PTX could improve the anti-glioma efficacy with a median survival time of 32 days, which was significantly longer than that of PTX-NP (23 days) and Taxol(®) (22 days). In conclusion, Pep-NP-PTX is a potential targeting drug delivery system for glioma treatment.

No MeSH data available.


Related in: MedlinePlus