Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer
In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanop...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Chaudhari, Dasharath [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Anmerkung: |
© Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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| Übergeordnetes Werk: |
Enthalten in: Drug Delivery and Translational Research - New York, NY [u.a.] : Springer, 2011, 13(2022), 4 vom: 17. Dez., Seite 1074-1087 |
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| Übergeordnetes Werk: |
volume:13 ; year:2022 ; number:4 ; day:17 ; month:12 ; pages:1074-1087 |
| Links: |
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| DOI / URN: |
10.1007/s13346-022-01273-9 |
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| Katalog-ID: |
SPR049530100 |
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| 520 | |a In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract | ||
| 650 | 4 | |a Adenosine |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Paclitaxel |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Triple-negative breast cancer |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a PLGA nanoparticles |7 (dpeaa)DE-He213 | |
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| 700 | 1 | |a Yadav, Vivek |4 aut | |
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| 700 | 1 | |a Bhargavi, Nallamothu |4 aut | |
| 700 | 1 | |a Jain, Sanyog |0 (orcid)0000-0002-0688-9563 |4 aut | |
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| 912 | |a GBV_ILN_2068 | ||
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10.1007/s13346-022-01273-9 doi (DE-627)SPR049530100 (SPR)s13346-022-01273-9-e DE-627 ger DE-627 rakwb eng Chaudhari, Dasharath verfasserin aut Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract Adenosine (dpeaa)DE-He213 Paclitaxel (dpeaa)DE-He213 Triple-negative breast cancer (dpeaa)DE-He213 PLGA nanoparticles (dpeaa)DE-He213 Adenosine receptor (dpeaa)DE-He213 Kuche, Kaushik aut Yadav, Vivek aut Ghadi, Rohan aut Date, Tushar aut Bhargavi, Nallamothu aut Jain, Sanyog (orcid)0000-0002-0688-9563 aut Enthalten in Drug Delivery and Translational Research New York, NY [u.a.] : Springer, 2011 13(2022), 4 vom: 17. Dez., Seite 1074-1087 (DE-627)644739592 (DE-600)2590155-2 2190-3948 nnns volume:13 year:2022 number:4 day:17 month:12 pages:1074-1087 https://dx.doi.org/10.1007/s13346-022-01273-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 4 17 12 1074-1087 |
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10.1007/s13346-022-01273-9 doi (DE-627)SPR049530100 (SPR)s13346-022-01273-9-e DE-627 ger DE-627 rakwb eng Chaudhari, Dasharath verfasserin aut Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract Adenosine (dpeaa)DE-He213 Paclitaxel (dpeaa)DE-He213 Triple-negative breast cancer (dpeaa)DE-He213 PLGA nanoparticles (dpeaa)DE-He213 Adenosine receptor (dpeaa)DE-He213 Kuche, Kaushik aut Yadav, Vivek aut Ghadi, Rohan aut Date, Tushar aut Bhargavi, Nallamothu aut Jain, Sanyog (orcid)0000-0002-0688-9563 aut Enthalten in Drug Delivery and Translational Research New York, NY [u.a.] : Springer, 2011 13(2022), 4 vom: 17. Dez., Seite 1074-1087 (DE-627)644739592 (DE-600)2590155-2 2190-3948 nnns volume:13 year:2022 number:4 day:17 month:12 pages:1074-1087 https://dx.doi.org/10.1007/s13346-022-01273-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 4 17 12 1074-1087 |
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10.1007/s13346-022-01273-9 doi (DE-627)SPR049530100 (SPR)s13346-022-01273-9-e DE-627 ger DE-627 rakwb eng Chaudhari, Dasharath verfasserin aut Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract Adenosine (dpeaa)DE-He213 Paclitaxel (dpeaa)DE-He213 Triple-negative breast cancer (dpeaa)DE-He213 PLGA nanoparticles (dpeaa)DE-He213 Adenosine receptor (dpeaa)DE-He213 Kuche, Kaushik aut Yadav, Vivek aut Ghadi, Rohan aut Date, Tushar aut Bhargavi, Nallamothu aut Jain, Sanyog (orcid)0000-0002-0688-9563 aut Enthalten in Drug Delivery and Translational Research New York, NY [u.a.] : Springer, 2011 13(2022), 4 vom: 17. Dez., Seite 1074-1087 (DE-627)644739592 (DE-600)2590155-2 2190-3948 nnns volume:13 year:2022 number:4 day:17 month:12 pages:1074-1087 https://dx.doi.org/10.1007/s13346-022-01273-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 4 17 12 1074-1087 |
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10.1007/s13346-022-01273-9 doi (DE-627)SPR049530100 (SPR)s13346-022-01273-9-e DE-627 ger DE-627 rakwb eng Chaudhari, Dasharath verfasserin aut Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract Adenosine (dpeaa)DE-He213 Paclitaxel (dpeaa)DE-He213 Triple-negative breast cancer (dpeaa)DE-He213 PLGA nanoparticles (dpeaa)DE-He213 Adenosine receptor (dpeaa)DE-He213 Kuche, Kaushik aut Yadav, Vivek aut Ghadi, Rohan aut Date, Tushar aut Bhargavi, Nallamothu aut Jain, Sanyog (orcid)0000-0002-0688-9563 aut Enthalten in Drug Delivery and Translational Research New York, NY [u.a.] : Springer, 2011 13(2022), 4 vom: 17. Dez., Seite 1074-1087 (DE-627)644739592 (DE-600)2590155-2 2190-3948 nnns volume:13 year:2022 number:4 day:17 month:12 pages:1074-1087 https://dx.doi.org/10.1007/s13346-022-01273-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 4 17 12 1074-1087 |
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10.1007/s13346-022-01273-9 doi (DE-627)SPR049530100 (SPR)s13346-022-01273-9-e DE-627 ger DE-627 rakwb eng Chaudhari, Dasharath verfasserin aut Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract Adenosine (dpeaa)DE-He213 Paclitaxel (dpeaa)DE-He213 Triple-negative breast cancer (dpeaa)DE-He213 PLGA nanoparticles (dpeaa)DE-He213 Adenosine receptor (dpeaa)DE-He213 Kuche, Kaushik aut Yadav, Vivek aut Ghadi, Rohan aut Date, Tushar aut Bhargavi, Nallamothu aut Jain, Sanyog (orcid)0000-0002-0688-9563 aut Enthalten in Drug Delivery and Translational Research New York, NY [u.a.] : Springer, 2011 13(2022), 4 vom: 17. Dez., Seite 1074-1087 (DE-627)644739592 (DE-600)2590155-2 2190-3948 nnns volume:13 year:2022 number:4 day:17 month:12 pages:1074-1087 https://dx.doi.org/10.1007/s13346-022-01273-9 lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_120 GBV_ILN_138 GBV_ILN_150 GBV_ILN_151 GBV_ILN_152 GBV_ILN_161 GBV_ILN_170 GBV_ILN_171 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_250 GBV_ILN_281 GBV_ILN_285 GBV_ILN_293 GBV_ILN_370 GBV_ILN_602 GBV_ILN_636 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2031 GBV_ILN_2034 GBV_ILN_2037 GBV_ILN_2038 GBV_ILN_2039 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2093 GBV_ILN_2106 GBV_ILN_2107 GBV_ILN_2108 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2144 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2188 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2446 GBV_ILN_2470 GBV_ILN_2472 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_2548 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4046 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4246 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4328 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4336 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 AR 13 2022 4 17 12 1074-1087 |
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Enthalten in Drug Delivery and Translational Research 13(2022), 4 vom: 17. Dez., Seite 1074-1087 volume:13 year:2022 number:4 day:17 month:12 pages:1074-1087 |
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Chaudhari, Dasharath @@aut@@ Kuche, Kaushik @@aut@@ Yadav, Vivek @@aut@@ Ghadi, Rohan @@aut@@ Date, Tushar @@aut@@ Bhargavi, Nallamothu @@aut@@ Jain, Sanyog @@aut@@ |
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Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. 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Chaudhari, Dasharath |
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Chaudhari, Dasharath misc Adenosine misc Paclitaxel misc Triple-negative breast cancer misc PLGA nanoparticles misc Adenosine receptor Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer |
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Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer Adenosine (dpeaa)DE-He213 Paclitaxel (dpeaa)DE-He213 Triple-negative breast cancer (dpeaa)DE-He213 PLGA nanoparticles (dpeaa)DE-He213 Adenosine receptor (dpeaa)DE-He213 |
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exploring paclitaxel-loaded adenosine-conjugated pegylated plga nanoparticles for targeting triple-negative breast cancer |
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Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer |
| abstract |
In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstractGer |
In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
| abstract_unstemmed |
In present investigation, we developed paclitaxel (PTX)-loaded adenosine (ADN)-conjugated PLGA nanoparticles for combating triple-negative breast cancer (TNBC), where ADN acts as a substrate for adenosine receptors (AR) that are overexpressed in TNBC. Using synthesized PLGA-PEG-ADN, PTX-loaded nanoparticles (PTX ADN-PEG-PLGA NPs) were prepared via emulsion diffusion evaporation process that rendered particles of size 135 ± 12 nm, PDI of 0.119 ± 0.03, and entrapment-efficiency of 79.26 ± 2.52%. The NPs showed higher %cumulative release at pH 5.5 over 7.4 with Higuchi release kinetics. The PTX ADN-PEG-PLGA NPs showed ~ 4.87- and 5.22-fold decrease in %hemolysis in comparison to free PTX and $ Intaxel^{®} $, indicating their hemocompatible nature. The ADN modification assisted cytoplasmic internalization of particles via AR-mediated endocytosis that resulted in ~ 3.77- and 3.51-fold reduction in $ IC_{50} $ and showed apoptosis index of 0.93 and 1.18 in MDA-MB-231 and 4T1 cells respectively. The pharmacokinetic profile of ADN-PEG-PLGA NPs revealed higher AUC and t1/2 than $ Intaxel^{®} $ and $ Nanoxel^{®} $ pharmacodynamic activity showed ~ 18.90-fold lower %tumor burden than control. The kidney and liver function biomarkers showed insignificant change in the levels, when treated with PTX ADN-PEG-PLGA NPs and exhibited no histological alterations in the liver, spleen, and kidney. Overall, the optimized particles were found to be biocompatible with improved anti-TNBC activity. Graphical Abstract © Controlled Release Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law. |
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Exploring paclitaxel-loaded adenosine-conjugated PEGylated PLGA nanoparticles for targeting triple-negative breast cancer |
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https://dx.doi.org/10.1007/s13346-022-01273-9 |
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Kuche, Kaushik Yadav, Vivek Ghadi, Rohan Date, Tushar Bhargavi, Nallamothu Jain, Sanyog |
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Kuche, Kaushik Yadav, Vivek Ghadi, Rohan Date, Tushar Bhargavi, Nallamothu Jain, Sanyog |
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10.1007/s13346-022-01273-9 |
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| score |
7.4006996 |