A pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine)-decorated liposome system for protein delivery: An application for bladder cancer treatment

Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (s...

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Vydané v:	Journal of controlled release Ročník 238; s. 31 - 42
Hlavní autori:	Vila-Caballer, Marian, Codolo, Gaia, Munari, Fabio, Malfanti, Alessio, Fassan, Matteo, Rugge, Massimo, Balasso, Anna, de Bernard, Marina, Salmaso, Stefano
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	Netherlands Elsevier B.V 28.09.2016
Predmet:	Animals Antineoplastic Agents - administration & dosage biopharmaceuticals bladder Bladder cancer treatment bovine serum albumin Cell Line, Tumor composite polymers confocal microscopy Delayed-Action Preparations - metabolism epithelium Epithelium - metabolism ethylene glycol Female fluorescein Fluorescein-5-isothiocyanate - administration & dosage Fluorescein-5-isothiocyanate - analogs & derivatives Hydrogen-Ion Concentration lipids Liposomes - metabolism macrophages Mice Mice, Inbred C57BL neoplasm cells pH-responsive liposomes photons Polyethylene Glycols - metabolism Polymethacrylic Acids - metabolism Protein delivery Serum Albumin, Bovine - administration & dosage soybeans spectroscopy sulfadimethoxine Sulfonamides - metabolism transmission electron microscopy Tumour targeting Urinary Bladder - metabolism urinary bladder neoplasms Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - metabolism urine zeta potential Protein delivery pH-responsive liposomes Tumour targeting Bladder cancer treatment
ISSN:	0168-3659, 1873-4995, 1873-4995
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Abstract	Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine+cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model. The loading capacity was 1.3% w/w BSA/lipid. At pH7.4, all liposome formulations displayed a negative zeta-potential and were stable for several days. By pH decrease or addition to mouse urine, the zeta potential strongly decreased, and the liposomes underwent a rapid size increase and aggregation. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) analyses showed that the extent of the aggregation depended on the stearoyl-PEG-polySDM/lipid molar ratio. Cytofluorimetric analysis and confocal microscopy showed that at pH6.5, the incubation of MB49 mouse bladder cancer cells and macrophages with fluorescein isothiocyanate-labelled-BSA (FITC-BSA) loaded and N-(Lissamine Rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (rhodamine-DHPE) labelled 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/lipid molar ratio liposomes resulted in a time-dependent liposome association with the cells. At pH7.4, the association of BSA-loaded liposomes with the MB49 cells and macrophages was remarkably lower than at pH6.5. Confocal images of bladder sections revealed that 2h after the instillation, liposomes at pH7.4 and control non-responsive liposomes at pH7.4 or 6.5 did not associate nor delivered FITC-BSA to the bladder epithelium. On the contrary, the pH-responsive liposome formulation set at pH6.5 and soon administered to mice by bladder instillation showed that, 2h after administration, the pH-responsive liposomes efficiently delivered the loaded FITC-BSA to the bladder epithelium. [Display omitted]
AbstractList	Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine+cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model. The loading capacity was 1.3% w/w BSA/lipid. At pH7.4, all liposome formulations displayed a negative zeta-potential and were stable for several days. By pH decrease or addition to mouse urine, the zeta potential strongly decreased, and the liposomes underwent a rapid size increase and aggregation. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) analyses showed that the extent of the aggregation depended on the stearoyl-PEG-polySDM/lipid molar ratio. Cytofluorimetric analysis and confocal microscopy showed that at pH6.5, the incubation of MB49 mouse bladder cancer cells and macrophages with fluorescein isothiocyanate-labelled-BSA (FITC-BSA) loaded and N-(Lissamine Rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (rhodamine-DHPE) labelled 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/lipid molar ratio liposomes resulted in a time-dependent liposome association with the cells. At pH7.4, the association of BSA-loaded liposomes with the MB49 cells and macrophages was remarkably lower than at pH6.5. Confocal images of bladder sections revealed that 2h after the instillation, liposomes at pH7.4 and control non-responsive liposomes at pH7.4 or 6.5 did not associate nor delivered FITC-BSA to the bladder epithelium. On the contrary, the pH-responsive liposome formulation set at pH6.5 and soon administered to mice by bladder instillation showed that, 2h after administration, the pH-responsive liposomes efficiently delivered the loaded FITC-BSA to the bladder epithelium. [Display omitted] Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine+cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model. The loading capacity was 1.3% w/w BSA/lipid. At pH7.4, all liposome formulations displayed a negative zeta-potential and were stable for several days. By pH decrease or addition to mouse urine, the zeta potential strongly decreased, and the liposomes underwent a rapid size increase and aggregation. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) analyses showed that the extent of the aggregation depended on the stearoyl-PEG-polySDM/lipid molar ratio. Cytofluorimetric analysis and confocal microscopy showed that at pH6.5, the incubation of MB49 mouse bladder cancer cells and macrophages with fluorescein isothiocyanate-labelled-BSA (FITC-BSA) loaded and N-(Lissamine Rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (rhodamine-DHPE) labelled 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/lipid molar ratio liposomes resulted in a time-dependent liposome association with the cells. At pH7.4, the association of BSA-loaded liposomes with the MB49 cells and macrophages was remarkably lower than at pH6.5. Confocal images of bladder sections revealed that 2h after the instillation, liposomes at pH7.4 and control non-responsive liposomes at pH7.4 or 6.5 did not associate nor delivered FITC-BSA to the bladder epithelium. On the contrary, the pH-responsive liposome formulation set at pH6.5 and soon administered to mice by bladder instillation showed that, 2h after administration, the pH-responsive liposomes efficiently delivered the loaded FITC-BSA to the bladder epithelium. Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine+cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model. The loading capacity was 1.3% w/w BSA/lipid. At pH7.4, all liposome formulations displayed a negative zeta-potential and were stable for several days. By pH decrease or addition to mouse urine, the zeta potential strongly decreased, and the liposomes underwent a rapid size increase and aggregation. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) analyses showed that the extent of the aggregation depended on the stearoyl-PEG-polySDM/lipid molar ratio. Cytofluorimetric analysis and confocal microscopy showed that at pH6.5, the incubation of MB49 mouse bladder cancer cells and macrophages with fluorescein isothiocyanate-labelled-BSA (FITC-BSA) loaded and N-(Lissamine Rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (rhodamine-DHPE) labelled 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/lipid molar ratio liposomes resulted in a time-dependent liposome association with the cells. At pH7.4, the association of BSA-loaded liposomes with the MB49 cells and macrophages was remarkably lower than at pH6.5. Confocal images of bladder sections revealed that 2h after the instillation, liposomes at pH7.4 and control non-responsive liposomes at pH7.4 or 6.5 did not associate nor delivered FITC-BSA to the bladder epithelium. On the contrary, the pH-responsive liposome formulation set at pH6.5 and soon administered to mice by bladder instillation showed that, 2h after administration, the pH-responsive liposomes efficiently delivered the loaded FITC-BSA to the bladder epithelium.Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene glycol)5kDa-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (mPEG5kDa-DSPE) and stearoyl-poly(ethylene glycol)-poly(methacryloyl sulfadimethoxine) copolymer (stearoyl-PEG-polySDM), which possesses an apparent pKa of 7.2. Liposomes of 0.2:0.6:100, 0.5:1.5:100 and 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/(soybean phosphatidylcholine+cholesterol) molar ratios were loaded with bovine serum albumin (BSA) as a protein model. The loading capacity was 1.3% w/w BSA/lipid. At pH7.4, all liposome formulations displayed a negative zeta-potential and were stable for several days. By pH decrease or addition to mouse urine, the zeta potential strongly decreased, and the liposomes underwent a rapid size increase and aggregation. Photon correlation spectroscopy (PCS) and transmission electron microscopy (TEM) analyses showed that the extent of the aggregation depended on the stearoyl-PEG-polySDM/lipid molar ratio. Cytofluorimetric analysis and confocal microscopy showed that at pH6.5, the incubation of MB49 mouse bladder cancer cells and macrophages with fluorescein isothiocyanate-labelled-BSA (FITC-BSA) loaded and N-(Lissamine Rhodamine B sulfonyl)-1, 2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine triethylammonium salt (rhodamine-DHPE) labelled 1:3:100 mPEG5kDa-DSPE/stearoyl-PEG-polySDM/lipid molar ratio liposomes resulted in a time-dependent liposome association with the cells. At pH7.4, the association of BSA-loaded liposomes with the MB49 cells and macrophages was remarkably lower than at pH6.5. Confocal images of bladder sections revealed that 2h after the instillation, liposomes at pH7.4 and control non-responsive liposomes at pH7.4 or 6.5 did not associate nor delivered FITC-BSA to the bladder epithelium. On the contrary, the pH-responsive liposome formulation set at pH6.5 and soon administered to mice by bladder instillation showed that, 2h after administration, the pH-responsive liposomes efficiently delivered the loaded FITC-BSA to the bladder epithelium.
Author	Codolo, Gaia Salmaso, Stefano Fassan, Matteo de Bernard, Marina Malfanti, Alessio Balasso, Anna Vila-Caballer, Marian Munari, Fabio Rugge, Massimo
Author_xml	– sequence: 1 givenname: Marian surname: Vila-Caballer fullname: Vila-Caballer, Marian organization: Department of Biology, University of Padova, Via U. Bassi 58/B, 35121 Padova, Italy – sequence: 2 givenname: Gaia surname: Codolo fullname: Codolo, Gaia organization: Department of Biology, University of Padova, Via U. Bassi 58/B, 35121 Padova, Italy – sequence: 3 givenname: Fabio surname: Munari fullname: Munari, Fabio organization: Department of Biomedical Sciences, University of Padova, Via U. Bassi 58/B, 35121 Padova, Italy – sequence: 4 givenname: Alessio surname: Malfanti fullname: Malfanti, Alessio organization: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131 Padova, Italy – sequence: 5 givenname: Matteo surname: Fassan fullname: Fassan, Matteo organization: Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padova, Via A. Gabelli 61, 35121 Padova, Italy – sequence: 6 givenname: Massimo surname: Rugge fullname: Rugge, Massimo organization: Surgical Pathology and Cytopathology Unit, Department of Medicine, University of Padova, Via A. Gabelli 61, 35121 Padova, Italy – sequence: 7 givenname: Anna surname: Balasso fullname: Balasso, Anna organization: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131 Padova, Italy – sequence: 8 givenname: Marina surname: de Bernard fullname: de Bernard, Marina email: marina.debernard@unipd.it organization: Department of Biology, University of Padova, Via U. Bassi 58/B, 35121 Padova, Italy – sequence: 9 givenname: Stefano surname: Salmaso fullname: Salmaso, Stefano email: stefano.salmaso@unipd.it organization: Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Via F. Marzolo 5, 35131 Padova, Italy
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/27444816$$D View this record in MEDLINE/PubMed
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Keywords	Protein delivery pH-responsive liposomes Tumour targeting Bladder cancer treatment
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Snippet	Stealth pH-responsive liposomes for the delivery of therapeutic proteins to the bladder epithelium were prepared using methoxy-poly(ethylene...
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SubjectTerms	Animals Antineoplastic Agents - administration & dosage biopharmaceuticals bladder Bladder cancer treatment bovine serum albumin Cell Line, Tumor composite polymers confocal microscopy Delayed-Action Preparations - metabolism epithelium Epithelium - metabolism ethylene glycol Female fluorescein Fluorescein-5-isothiocyanate - administration & dosage Fluorescein-5-isothiocyanate - analogs & derivatives Hydrogen-Ion Concentration lipids Liposomes - metabolism macrophages Mice Mice, Inbred C57BL neoplasm cells pH-responsive liposomes photons Polyethylene Glycols - metabolism Polymethacrylic Acids - metabolism Protein delivery Serum Albumin, Bovine - administration & dosage soybeans spectroscopy sulfadimethoxine Sulfonamides - metabolism transmission electron microscopy Tumour targeting Urinary Bladder - metabolism urinary bladder neoplasms Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - metabolism urine zeta potential
Title	A pH-sensitive stearoyl-PEG-poly(methacryloyl sulfadimethoxine)-decorated liposome system for protein delivery: An application for bladder cancer treatment
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