Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma
The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective th...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Janjua, Taskeen Iqbal [verfasserIn] Cao, Yuxue [verfasserIn] Ahmed-Cox, Aria [verfasserIn] Raza, Aun [verfasserIn] Moniruzzaman, Md [verfasserIn] Akhter, Dewan Taslima [verfasserIn] Fletcher, Nicholas L. [verfasserIn] Kavallaris, Maria [verfasserIn] Thurecht, Kristofer J. [verfasserIn] Popat, Amirali [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Journal of controlled release - New York, NY [u.a.] : Elsevier, 1984, 357, Seite 161-174 |
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| Übergeordnetes Werk: |
volume:357 ; pages:161-174 |
| DOI / URN: |
10.1016/j.jconrel.2023.03.040 |
|---|
| Katalog-ID: |
ELV061104833 |
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| 245 | 1 | 0 | |a Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
| 264 | 1 | |c 2023 | |
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| 520 | |a The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. | ||
| 650 | 4 | |a Glioblastoma | |
| 650 | 4 | |a Targeted drug delivery | |
| 650 | 4 | |a Blood brain barrier | |
| 650 | 4 | |a Mesoporous silica | |
| 650 | 4 | |a Lactoferrin | |
| 650 | 4 | |a Temozolomide | |
| 650 | 4 | |a Large pore | |
| 650 | 4 | |a Ultra-small nanoparticle | |
| 650 | 4 | |a Silica functionalisation | |
| 650 | 4 | |a 3D glioblastoma model | |
| 650 | 4 | |a Optical imaging | |
| 650 | 4 | |a Brain imaging | |
| 700 | 1 | |a Cao, Yuxue |e verfasserin |4 aut | |
| 700 | 1 | |a Ahmed-Cox, Aria |e verfasserin |4 aut | |
| 700 | 1 | |a Raza, Aun |e verfasserin |4 aut | |
| 700 | 1 | |a Moniruzzaman, Md |e verfasserin |4 aut | |
| 700 | 1 | |a Akhter, Dewan Taslima |e verfasserin |4 aut | |
| 700 | 1 | |a Fletcher, Nicholas L. |e verfasserin |4 aut | |
| 700 | 1 | |a Kavallaris, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Thurecht, Kristofer J. |e verfasserin |4 aut | |
| 700 | 1 | |a Popat, Amirali |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of controlled release |d New York, NY [u.a.] : Elsevier, 1984 |g 357, Seite 161-174 |h Online-Ressource |w (DE-627)300589220 |w (DE-600)1482453-X |w (DE-576)081952589 |x 1873-4995 |7 nnns |
| 773 | 1 | 8 | |g volume:357 |g pages:161-174 |
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| 912 | |a GBV_ILN_2009 | ||
| 912 | |a GBV_ILN_2010 | ||
| 912 | |a GBV_ILN_2011 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2015 | ||
| 912 | |a GBV_ILN_2020 | ||
| 912 | |a GBV_ILN_2021 | ||
| 912 | |a GBV_ILN_2025 | ||
| 912 | |a GBV_ILN_2026 | ||
| 912 | |a GBV_ILN_2027 | ||
| 912 | |a GBV_ILN_2034 | ||
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| 912 | |a GBV_ILN_2048 | ||
| 912 | |a GBV_ILN_2049 | ||
| 912 | |a GBV_ILN_2050 | ||
| 912 | |a GBV_ILN_2055 | ||
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| 912 | |a GBV_ILN_2059 | ||
| 912 | |a GBV_ILN_2061 | ||
| 912 | |a GBV_ILN_2064 | ||
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| 912 | |a GBV_ILN_2106 | ||
| 912 | |a GBV_ILN_2110 | ||
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| 912 | |a GBV_ILN_2153 | ||
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| 912 | |a GBV_ILN_2232 | ||
| 912 | |a GBV_ILN_2336 | ||
| 912 | |a GBV_ILN_2470 | ||
| 912 | |a GBV_ILN_2507 | ||
| 912 | |a GBV_ILN_4035 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
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| 912 | |a GBV_ILN_4249 | ||
| 912 | |a GBV_ILN_4251 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4306 | ||
| 912 | |a GBV_ILN_4307 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4322 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4326 | ||
| 912 | |a GBV_ILN_4333 | ||
| 912 | |a GBV_ILN_4334 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4393 | ||
| 912 | |a GBV_ILN_4700 | ||
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10.1016/j.jconrel.2023.03.040 doi (DE-627)ELV061104833 (ELSEVIER)S0168-3659(23)00207-9 DE-627 ger DE-627 rda eng 540 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl 58.28 bkl Janjua, Taskeen Iqbal verfasserin aut Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. Glioblastoma Targeted drug delivery Blood brain barrier Mesoporous silica Lactoferrin Temozolomide Large pore Ultra-small nanoparticle Silica functionalisation 3D glioblastoma model Optical imaging Brain imaging Cao, Yuxue verfasserin aut Ahmed-Cox, Aria verfasserin aut Raza, Aun verfasserin aut Moniruzzaman, Md verfasserin aut Akhter, Dewan Taslima verfasserin aut Fletcher, Nicholas L. verfasserin aut Kavallaris, Maria verfasserin aut Thurecht, Kristofer J. verfasserin aut Popat, Amirali verfasserin aut Enthalten in Journal of controlled release New York, NY [u.a.] : Elsevier, 1984 357, Seite 161-174 Online-Ressource (DE-627)300589220 (DE-600)1482453-X (DE-576)081952589 1873-4995 nnns volume:357 pages:161-174 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 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_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 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_2034 GBV_ILN_2037 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 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_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ 58.28 Pharmazeutische Technologie VZ AR 357 161-174 |
| spelling |
10.1016/j.jconrel.2023.03.040 doi (DE-627)ELV061104833 (ELSEVIER)S0168-3659(23)00207-9 DE-627 ger DE-627 rda eng 540 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl 58.28 bkl Janjua, Taskeen Iqbal verfasserin aut Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. Glioblastoma Targeted drug delivery Blood brain barrier Mesoporous silica Lactoferrin Temozolomide Large pore Ultra-small nanoparticle Silica functionalisation 3D glioblastoma model Optical imaging Brain imaging Cao, Yuxue verfasserin aut Ahmed-Cox, Aria verfasserin aut Raza, Aun verfasserin aut Moniruzzaman, Md verfasserin aut Akhter, Dewan Taslima verfasserin aut Fletcher, Nicholas L. verfasserin aut Kavallaris, Maria verfasserin aut Thurecht, Kristofer J. verfasserin aut Popat, Amirali verfasserin aut Enthalten in Journal of controlled release New York, NY [u.a.] : Elsevier, 1984 357, Seite 161-174 Online-Ressource (DE-627)300589220 (DE-600)1482453-X (DE-576)081952589 1873-4995 nnns volume:357 pages:161-174 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 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_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 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_2034 GBV_ILN_2037 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 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_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ 58.28 Pharmazeutische Technologie VZ AR 357 161-174 |
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10.1016/j.jconrel.2023.03.040 doi (DE-627)ELV061104833 (ELSEVIER)S0168-3659(23)00207-9 DE-627 ger DE-627 rda eng 540 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl 58.28 bkl Janjua, Taskeen Iqbal verfasserin aut Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. Glioblastoma Targeted drug delivery Blood brain barrier Mesoporous silica Lactoferrin Temozolomide Large pore Ultra-small nanoparticle Silica functionalisation 3D glioblastoma model Optical imaging Brain imaging Cao, Yuxue verfasserin aut Ahmed-Cox, Aria verfasserin aut Raza, Aun verfasserin aut Moniruzzaman, Md verfasserin aut Akhter, Dewan Taslima verfasserin aut Fletcher, Nicholas L. verfasserin aut Kavallaris, Maria verfasserin aut Thurecht, Kristofer J. verfasserin aut Popat, Amirali verfasserin aut Enthalten in Journal of controlled release New York, NY [u.a.] : Elsevier, 1984 357, Seite 161-174 Online-Ressource (DE-627)300589220 (DE-600)1482453-X (DE-576)081952589 1873-4995 nnns volume:357 pages:161-174 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 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_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 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_2034 GBV_ILN_2037 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 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_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ 58.28 Pharmazeutische Technologie VZ AR 357 161-174 |
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10.1016/j.jconrel.2023.03.040 doi (DE-627)ELV061104833 (ELSEVIER)S0168-3659(23)00207-9 DE-627 ger DE-627 rda eng 540 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl 58.28 bkl Janjua, Taskeen Iqbal verfasserin aut Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. Glioblastoma Targeted drug delivery Blood brain barrier Mesoporous silica Lactoferrin Temozolomide Large pore Ultra-small nanoparticle Silica functionalisation 3D glioblastoma model Optical imaging Brain imaging Cao, Yuxue verfasserin aut Ahmed-Cox, Aria verfasserin aut Raza, Aun verfasserin aut Moniruzzaman, Md verfasserin aut Akhter, Dewan Taslima verfasserin aut Fletcher, Nicholas L. verfasserin aut Kavallaris, Maria verfasserin aut Thurecht, Kristofer J. verfasserin aut Popat, Amirali verfasserin aut Enthalten in Journal of controlled release New York, NY [u.a.] : Elsevier, 1984 357, Seite 161-174 Online-Ressource (DE-627)300589220 (DE-600)1482453-X (DE-576)081952589 1873-4995 nnns volume:357 pages:161-174 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 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_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 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_2034 GBV_ILN_2037 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 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_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ 58.28 Pharmazeutische Technologie VZ AR 357 161-174 |
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10.1016/j.jconrel.2023.03.040 doi (DE-627)ELV061104833 (ELSEVIER)S0168-3659(23)00207-9 DE-627 ger DE-627 rda eng 540 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl 58.28 bkl Janjua, Taskeen Iqbal verfasserin aut Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. Glioblastoma Targeted drug delivery Blood brain barrier Mesoporous silica Lactoferrin Temozolomide Large pore Ultra-small nanoparticle Silica functionalisation 3D glioblastoma model Optical imaging Brain imaging Cao, Yuxue verfasserin aut Ahmed-Cox, Aria verfasserin aut Raza, Aun verfasserin aut Moniruzzaman, Md verfasserin aut Akhter, Dewan Taslima verfasserin aut Fletcher, Nicholas L. verfasserin aut Kavallaris, Maria verfasserin aut Thurecht, Kristofer J. verfasserin aut Popat, Amirali verfasserin aut Enthalten in Journal of controlled release New York, NY [u.a.] : Elsevier, 1984 357, Seite 161-174 Online-Ressource (DE-627)300589220 (DE-600)1482453-X (DE-576)081952589 1873-4995 nnns volume:357 pages:161-174 GBV_USEFLAG_U GBV_ELV SYSFLAG_U FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 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_150 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 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_2034 GBV_ILN_2037 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4242 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_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ 58.28 Pharmazeutische Technologie VZ AR 357 161-174 |
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Janjua, Taskeen Iqbal @@aut@@ Cao, Yuxue @@aut@@ Ahmed-Cox, Aria @@aut@@ Raza, Aun @@aut@@ Moniruzzaman, Md @@aut@@ Akhter, Dewan Taslima @@aut@@ Fletcher, Nicholas L. @@aut@@ Kavallaris, Maria @@aut@@ Thurecht, Kristofer J. @@aut@@ Popat, Amirali @@aut@@ |
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Janjua, Taskeen Iqbal |
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Janjua, Taskeen Iqbal ddc 540 ssgn 15,3 fid PHARM bkl 44.40 bkl 58.28 misc Glioblastoma misc Targeted drug delivery misc Blood brain barrier misc Mesoporous silica misc Lactoferrin misc Temozolomide misc Large pore misc Ultra-small nanoparticle misc Silica functionalisation misc 3D glioblastoma model misc Optical imaging misc Brain imaging Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
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540 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl 58.28 bkl Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma Glioblastoma Targeted drug delivery Blood brain barrier Mesoporous silica Lactoferrin Temozolomide Large pore Ultra-small nanoparticle Silica functionalisation 3D glioblastoma model Optical imaging Brain imaging |
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ddc 540 ssgn 15,3 fid PHARM bkl 44.40 bkl 58.28 misc Glioblastoma misc Targeted drug delivery misc Blood brain barrier misc Mesoporous silica misc Lactoferrin misc Temozolomide misc Large pore misc Ultra-small nanoparticle misc Silica functionalisation misc 3D glioblastoma model misc Optical imaging misc Brain imaging |
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ddc 540 ssgn 15,3 fid PHARM bkl 44.40 bkl 58.28 misc Glioblastoma misc Targeted drug delivery misc Blood brain barrier misc Mesoporous silica misc Lactoferrin misc Temozolomide misc Large pore misc Ultra-small nanoparticle misc Silica functionalisation misc 3D glioblastoma model misc Optical imaging misc Brain imaging |
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ddc 540 ssgn 15,3 fid PHARM bkl 44.40 bkl 58.28 misc Glioblastoma misc Targeted drug delivery misc Blood brain barrier misc Mesoporous silica misc Lactoferrin misc Temozolomide misc Large pore misc Ultra-small nanoparticle misc Silica functionalisation misc 3D glioblastoma model misc Optical imaging misc Brain imaging |
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Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
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Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
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Janjua, Taskeen Iqbal Cao, Yuxue Ahmed-Cox, Aria Raza, Aun Moniruzzaman, Md Akhter, Dewan Taslima Fletcher, Nicholas L. Kavallaris, Maria Thurecht, Kristofer J. Popat, Amirali |
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efficient delivery of temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
| title_auth |
Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
| abstract |
The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. |
| abstractGer |
The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. |
| abstract_unstemmed |
The prognosis of brain cancers such as glioblastoma remains poor despite numerous advancements in the field of neuro-oncology. The presence of the blood brain barrier (BBB) along with the highly invasive and aggressive nature of glioblastoma presents a difficult challenge for developing effective therapies. Temozolomide (TMZ) is a first line agent used in the clinic for glioblastoma and it has been useful in increasing patient survival rates. However, TMZ suffers from issues related to its pharmacokinetics, such as a short plasma half-life (2 h), is subjected to P-gp efflux, and has limited extravasation from blood to brain (∼20%). It has been postulated that reducing its efflux and increasing glioblastoma tissue exposure to TMZ could prove useful in treating glioblastoma and preventing tumour recurrence. Herein, ultra-small, large pore silica nanoparticles (USLP) have been loaded with TMZ, surface PEGlyated to reduce efflux and decorated with the cascade targeting protein lactoferrin for efficient uptake across the BBB and into glioblastoma. Our results demonstrate that USLP improves permeability of BBB in vitro as evidenced using a transwell model which mimics endothelial tight junctions with permeation being enhanced using PEGylated particles. Data from TMZ loaded USLP in vitro transwell BBB model also suggests that the USLP formulations can significantly reduce the efflux ratio of TMZ. In vitro apoptosis studies on glioblastoma cell lines U87 and GL261 were conducted which showed an improvement in TMZ induced glioblastoma apoptosis with USLP formulations compared to pure TMZ. Finally, a proof-of-concept preclinical mouse study demonstrated that when given intravenously at 50 mg/kg, USLP particles showed accumulation in the brain within a few hours without any obvious pathophysiological changes in vital organs as assessed via histology. Overall, the data suggests our innovative delivery system is efficient in extravasation from blood and permeating the BBB and has potential to improve efficacy of TMZ in glioblastoma therapy. |
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Efficient delivery of Temozolomide using ultrasmall large-pore silica nanoparticles for glioblastoma |
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Cao, Yuxue Ahmed-Cox, Aria Raza, Aun Moniruzzaman, Md Akhter, Dewan Taslima Fletcher, Nicholas L. Kavallaris, Maria Thurecht, Kristofer J. Popat, Amirali |
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Cao, Yuxue Ahmed-Cox, Aria Raza, Aun Moniruzzaman, Md Akhter, Dewan Taslima Fletcher, Nicholas L. Kavallaris, Maria Thurecht, Kristofer J. Popat, Amirali |
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| doi_str |
10.1016/j.jconrel.2023.03.040 |
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2024-07-06T17:13:14.972Z |
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