Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy
The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Kushwah, Varun [verfasserIn] |
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E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2018transfer abstract |
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| Umfang: |
13 |
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| Übergeordnetes Werk: |
Enthalten in: Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu - Shen, Zhen ELSEVIER, 2022, New York, NY |
|---|---|
| Übergeordnetes Werk: |
volume:14 ; year:2018 ; number:5 ; pages:1629-1641 ; extent:13 |
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| DOI / URN: |
10.1016/j.nano.2018.04.009 |
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| 520 | |a The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. | ||
| 520 | |a The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. | ||
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| 700 | 1 | |a Jain, Sanyog |4 oth | |
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10.1016/j.nano.2018.04.009 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000869.pica (DE-627)ELV04373765X (ELSEVIER)S1549-9634(18)30081-9 DE-627 ger DE-627 rakwb eng 333.7 570 690 VZ BIODIV DE-30 fid 48.00 bkl Kushwah, Varun verfasserin aut Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy 2018transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Katiyar, Sameer S. oth Agrawal, Ashish Kumar oth Gupta, Ramesh C. oth Jain, Sanyog oth Enthalten in Elsevier Shen, Zhen ELSEVIER Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu 2022 New York, NY (DE-627)ELV008639612 volume:14 year:2018 number:5 pages:1629-1641 extent:13 https://doi.org/10.1016/j.nano.2018.04.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 14 2018 5 1629-1641 13 |
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10.1016/j.nano.2018.04.009 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000869.pica (DE-627)ELV04373765X (ELSEVIER)S1549-9634(18)30081-9 DE-627 ger DE-627 rakwb eng 333.7 570 690 VZ BIODIV DE-30 fid 48.00 bkl Kushwah, Varun verfasserin aut Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy 2018transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Katiyar, Sameer S. oth Agrawal, Ashish Kumar oth Gupta, Ramesh C. oth Jain, Sanyog oth Enthalten in Elsevier Shen, Zhen ELSEVIER Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu 2022 New York, NY (DE-627)ELV008639612 volume:14 year:2018 number:5 pages:1629-1641 extent:13 https://doi.org/10.1016/j.nano.2018.04.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 14 2018 5 1629-1641 13 |
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10.1016/j.nano.2018.04.009 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000869.pica (DE-627)ELV04373765X (ELSEVIER)S1549-9634(18)30081-9 DE-627 ger DE-627 rakwb eng 333.7 570 690 VZ BIODIV DE-30 fid 48.00 bkl Kushwah, Varun verfasserin aut Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy 2018transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Katiyar, Sameer S. oth Agrawal, Ashish Kumar oth Gupta, Ramesh C. oth Jain, Sanyog oth Enthalten in Elsevier Shen, Zhen ELSEVIER Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu 2022 New York, NY (DE-627)ELV008639612 volume:14 year:2018 number:5 pages:1629-1641 extent:13 https://doi.org/10.1016/j.nano.2018.04.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 14 2018 5 1629-1641 13 |
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10.1016/j.nano.2018.04.009 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000869.pica (DE-627)ELV04373765X (ELSEVIER)S1549-9634(18)30081-9 DE-627 ger DE-627 rakwb eng 333.7 570 690 VZ BIODIV DE-30 fid 48.00 bkl Kushwah, Varun verfasserin aut Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy 2018transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Katiyar, Sameer S. oth Agrawal, Ashish Kumar oth Gupta, Ramesh C. oth Jain, Sanyog oth Enthalten in Elsevier Shen, Zhen ELSEVIER Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu 2022 New York, NY (DE-627)ELV008639612 volume:14 year:2018 number:5 pages:1629-1641 extent:13 https://doi.org/10.1016/j.nano.2018.04.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 14 2018 5 1629-1641 13 |
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10.1016/j.nano.2018.04.009 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000000869.pica (DE-627)ELV04373765X (ELSEVIER)S1549-9634(18)30081-9 DE-627 ger DE-627 rakwb eng 333.7 570 690 VZ BIODIV DE-30 fid 48.00 bkl Kushwah, Varun verfasserin aut Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy 2018transfer abstract 13 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. Katiyar, Sameer S. oth Agrawal, Ashish Kumar oth Gupta, Ramesh C. oth Jain, Sanyog oth Enthalten in Elsevier Shen, Zhen ELSEVIER Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu 2022 New York, NY (DE-627)ELV008639612 volume:14 year:2018 number:5 pages:1629-1641 extent:13 https://doi.org/10.1016/j.nano.2018.04.009 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-BIODIV SSG-OLC-PHA SSG-OPC-FOR 48.00 Land- und Forstwirtschaft: Allgemeines VZ AR 14 2018 5 1629-1641 13 |
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Enthalten in Similar assembly mechanisms but distinct co-occurrence patterns of free-living vs. particle-attached bacterial communities across different habitats and seasons in shallow, eutrophic Lake Taihu New York, NY volume:14 year:2018 number:5 pages:1629-1641 extent:13 |
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co-delivery of docetaxel and gemcitabine using pegylated self-assembled stealth nanoparticles for improved breast cancer therapy |
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Co-delivery of docetaxel and gemcitabine using PEGylated self-assembled stealth nanoparticles for improved breast cancer therapy |
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The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. |
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The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. |
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The present report deals with conjugation of dual drug; docetaxel (DTX) and gemcitabine (GEM) with linker poly-ethylene-glycol (PEG) to develop amphiphilic molecule having self-assembled property. The synthesized conjugate (DTX-PEG-GEM) demonstrated critical micelle concentration (CMC) in the range of 5–10 μg/ml which self-assembled to form NPs with size 124.2 ± 5.7. Remarkably higher coumarin-6 (C-6) fluorescence signals observed in case of C-6 loaded NPs, suggested enhanced cellular uptake via clathrin mediated endocytosis. Developed NPs demonstrated 4.8-fold higher AUC(0-∞) value of GEM in comparison with Gemzar®. Tumor growth inhibition study demonstrated significant reduction in tumor volume and higher survival rate with NPs. Moreover, NPs demonstrated significantly lower hepato- and nephro-toxicity, evident from both histopathological sections and biochemical markers level estimation, and hemolytic toxicity. Data in hand suggest enhanced therapeutic efficacy and reduced toxicity of developed NPs over conventional drugs, resulting in efficient combinatorial chemotherapeutic-regimen and patient compliance, which is still an unmet task. |
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