TY  - JOUR
AU  - Cvjetinović, Đorđe
AU  - Pan, Xiaohan
AU  - Petrović, Jelena
AU  - Schumann, Dorothea
PY  - 2024
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/13179
AB  - Sorption and desorption of Al(III) on a series of different extraction resins (LN, LN2, LN3, TK100, TK101, TK201) in acidic HNO3 media containing high concentrations of V(IV,V) was investigated. Static batch studies were conducted as a way of obtaining preliminary distribution coefficient (Kd) values that were further used to develop dynamic tests on real samples. It was shown that a complete separation and recovery of Al(III) from V(V) under acidic conditions (pH = 2) is possible by utilizing LN resin. Active “hot” dynamic studies with 26Al (≈10 Bq) as a radiotracer and real waste samples were conducted to further investigate and confirm the results of the inactive “cold” experiments. Utilizing this separation procedure, we have successfully removed all traces of 26Al (∼10−9 g) radiotracer from the bulk vanadium matrix.
T2  - Microchemical Journal
T1  - Optimizing a radiochemical separation of 26Al from an acidic V-rich matrix
VL  - 200
SP  - 110477
DO  - 10.1016/j.microc.2024.110477
ER  - 

@article{
author = "Cvjetinović, Đorđe and Pan, Xiaohan and Petrović, Jelena and Schumann, Dorothea",
year = "2024",
abstract = "Sorption and desorption of Al(III) on a series of different extraction resins (LN, LN2, LN3, TK100, TK101, TK201) in acidic HNO3 media containing high concentrations of V(IV,V) was investigated. Static batch studies were conducted as a way of obtaining preliminary distribution coefficient (Kd) values that were further used to develop dynamic tests on real samples. It was shown that a complete separation and recovery of Al(III) from V(V) under acidic conditions (pH = 2) is possible by utilizing LN resin. Active “hot” dynamic studies with 26Al (≈10 Bq) as a radiotracer and real waste samples were conducted to further investigate and confirm the results of the inactive “cold” experiments. Utilizing this separation procedure, we have successfully removed all traces of 26Al (∼10−9 g) radiotracer from the bulk vanadium matrix.",
journal = "Microchemical Journal",
title = "Optimizing a radiochemical separation of 26Al from an acidic V-rich matrix",
volume = "200",
pages = "110477",
doi = "10.1016/j.microc.2024.110477"
}

Cvjetinović, Đ., Pan, X., Petrović, J.,& Schumann, D.. (2024). Optimizing a radiochemical separation of 26Al from an acidic V-rich matrix. in Microchemical Journal, 200, 110477.
https://doi.org/10.1016/j.microc.2024.110477

Cvjetinović Đ, Pan X, Petrović J, Schumann D. Optimizing a radiochemical separation of 26Al from an acidic V-rich matrix. in Microchemical Journal. 2024;200:110477.
doi:10.1016/j.microc.2024.110477 .

Cvjetinović, Đorđe, Pan, Xiaohan, Petrović, Jelena, Schumann, Dorothea, "Optimizing a radiochemical separation of 26Al from an acidic V-rich matrix" in Microchemical Journal, 200 (2024):110477,
https://doi.org/10.1016/j.microc.2024.110477 . .

TY  - CONF
AU  - Cvjetinović, Đorđe
AU  - Milanović, Zorana
AU  - Mirković, Marija
AU  - Petrović, Jelena D.
AU  - Vesković, Ana
AU  - Popović-Bijelić, Ana
AU  - Janković, Drina
AU  - Vranješ-Đurić, Sanja
PY  - 2022
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12661
AB  - Novel methods of cancer therapy are constantly being investigated since the current approach heavily relies on the use of non-specific and toxic chemotherapy agents. Ideally, a drug used for cancer therapy would specifically target tumor sites or rather bind specifically with cancer cells. The way to achieve this is by targeting cancer cell specific receptors or receptors present in abnormally high counts at the surface. Rapid proliferation of cancer cells is fueled by large amounts of energy that is in turn produced by abnormal glucose uptake. Because of this high energy/glucose demand, cancer cells exhibit an abnormally high glucose receptor (GLUTs) count on their surface, compared to normal, healthy cells. We have utilized this glucose dependency to create glucose modified liposomes (Glucosomes) that are specifically bound by cancer cells. Glucosomes can be used to transport different substances, either hydrophilic or hydrophobic, and can therefore deliver any type of drug to cancer cells, increasing its efficiency. Another important aspect to consider is the controlled release of the drug being transported in order to maximize therapeutic efficiency. Controlled release can be achieved by utilizing different internal or external influences. In our study, we have used standard Fe3O4 magnetic nanoparticles to load glucosomes and induce their controlled opening via an external magnetic field. By applying an external magnetic field, the magnetic nanoparticles start heating up and transferring this thermal energy to the surrounding lipid bilayer, causing its perturbation and opening of the glucosome. Our study has found that controlled release can be achieved with high efficiency while the chemical stability of the Fe3O4 nanoparticles stays practically intact. Using EPR spectroscopy, we have shown that Fe3O4 nanoparticles remain trapped within the lipid bilayer and are essentially protected from oxidation that would diminish their magnetic properties. Since magnetic Fe3O4 nanoparticles are lodged well within the lipid bilayer no thermal damage can be caused to the drug being transported within the glucosome bilayer, making this a viable controlled release cancer targeting drug delivery system.
PB  - Belgrade : Institute of Technical Sciences of SASA
C3  - 20th Young Researchers' Conference Materials Sciences and Engineering : program and the book of abstracts
T1  - Glucosomes: Magnetically induced controlled release of glucose modified liposomes
SP  - 12
EP  - 12
UR  - https://hdl.handle.net/21.15107/rcub_vinar_12661
ER  - 

@conference{
author = "Cvjetinović, Đorđe and Milanović, Zorana and Mirković, Marija and Petrović, Jelena D. and Vesković, Ana and Popović-Bijelić, Ana and Janković, Drina and Vranješ-Đurić, Sanja",
year = "2022",
abstract = "Novel methods of cancer therapy are constantly being investigated since the current approach heavily relies on the use of non-specific and toxic chemotherapy agents. Ideally, a drug used for cancer therapy would specifically target tumor sites or rather bind specifically with cancer cells. The way to achieve this is by targeting cancer cell specific receptors or receptors present in abnormally high counts at the surface. Rapid proliferation of cancer cells is fueled by large amounts of energy that is in turn produced by abnormal glucose uptake. Because of this high energy/glucose demand, cancer cells exhibit an abnormally high glucose receptor (GLUTs) count on their surface, compared to normal, healthy cells. We have utilized this glucose dependency to create glucose modified liposomes (Glucosomes) that are specifically bound by cancer cells. Glucosomes can be used to transport different substances, either hydrophilic or hydrophobic, and can therefore deliver any type of drug to cancer cells, increasing its efficiency. Another important aspect to consider is the controlled release of the drug being transported in order to maximize therapeutic efficiency. Controlled release can be achieved by utilizing different internal or external influences. In our study, we have used standard Fe3O4 magnetic nanoparticles to load glucosomes and induce their controlled opening via an external magnetic field. By applying an external magnetic field, the magnetic nanoparticles start heating up and transferring this thermal energy to the surrounding lipid bilayer, causing its perturbation and opening of the glucosome. Our study has found that controlled release can be achieved with high efficiency while the chemical stability of the Fe3O4 nanoparticles stays practically intact. Using EPR spectroscopy, we have shown that Fe3O4 nanoparticles remain trapped within the lipid bilayer and are essentially protected from oxidation that would diminish their magnetic properties. Since magnetic Fe3O4 nanoparticles are lodged well within the lipid bilayer no thermal damage can be caused to the drug being transported within the glucosome bilayer, making this a viable controlled release cancer targeting drug delivery system.",
publisher = "Belgrade : Institute of Technical Sciences of SASA",
journal = "20th Young Researchers' Conference Materials Sciences and Engineering : program and the book of abstracts",
title = "Glucosomes: Magnetically induced controlled release of glucose modified liposomes",
pages = "12-12",
url = "https://hdl.handle.net/21.15107/rcub_vinar_12661"
}

Cvjetinović, Đ., Milanović, Z., Mirković, M., Petrović, J. D., Vesković, A., Popović-Bijelić, A., Janković, D.,& Vranješ-Đurić, S.. (2022). Glucosomes: Magnetically induced controlled release of glucose modified liposomes. in 20th Young Researchers' Conference Materials Sciences and Engineering : program and the book of abstracts
Belgrade : Institute of Technical Sciences of SASA., 12-12.
https://hdl.handle.net/21.15107/rcub_vinar_12661

Cvjetinović Đ, Milanović Z, Mirković M, Petrović JD, Vesković A, Popović-Bijelić A, Janković D, Vranješ-Đurić S. Glucosomes: Magnetically induced controlled release of glucose modified liposomes. in 20th Young Researchers' Conference Materials Sciences and Engineering : program and the book of abstracts. 2022;:12-12.
https://hdl.handle.net/21.15107/rcub_vinar_12661 .

Cvjetinović, Đorđe, Milanović, Zorana, Mirković, Marija, Petrović, Jelena D., Vesković, Ana, Popović-Bijelić, Ana, Janković, Drina, Vranješ-Đurić, Sanja, "Glucosomes: Magnetically induced controlled release of glucose modified liposomes" in 20th Young Researchers' Conference Materials Sciences and Engineering : program and the book of abstracts (2022):12-12,
https://hdl.handle.net/21.15107/rcub_vinar_12661 .

TY  - JOUR
AU  - Cvjetinović, Đorđe
AU  - Milanović, Zorana
AU  - Mirković, Marija D.
AU  - Petrović, Jelena
AU  - Vesković, Ana
AU  - Popović-Bijelić, Ana
AU  - Prijović, Željko
AU  - Janković, Drina
AU  - Vranješ-Đurić, Sanja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/10063
AB  - Small glucose-modified liposomes (GMLs) were loaded with magnetic Fe3O4 nanoparticles (MNPs) and fluorescein using a standard thin layer preparation procedure and a varying lipid/MNPs ratio. The liposomes were characterized with TEM and DLS measurements, and MNPs encapsulation rate was determined using ICP-OES. Prepared liposomes were stored at 5 °C for 30 days and subsequently exposed to an external magnetic field (20 mT) with varying exposure times (2‒20 min), at room temperature. The release of fluorescein from GMLs induced by the magnetic field exposures was quantified, showing a high release rate (25‒85%) depending on the concentration of MNPs in GMLs. EPR measurements were conducted during the liposomes storage period in order to provide semi-quantitative information of possible MNPs oxidation from Fe3O4 to Fe2O3 inside the liposomes, impacting MNPs magnetic properties. In contrast to the MNPs water dispersion, no significant change in the EPR signal of MNPs encapsulated inside GMLs was detected over the course of 30 days. The data presented in this study indicate that GMLs loaded with MNPs maintain a high stability for prolonged periods of time and that this delivery system may be used for magnetically assisted controlled drug release.
T2  - Journal of Nanoparticle Research
T1  - Magnetically induced controlled release from glucose-modified liposomes loaded with Fe3O4 nanoparticles
VL  - 23
IS  - 11
SP  - 252
DO  - 10.1007/s11051-021-05375-2
ER  - 

@article{
author = "Cvjetinović, Đorđe and Milanović, Zorana and Mirković, Marija D. and Petrović, Jelena and Vesković, Ana and Popović-Bijelić, Ana and Prijović, Željko and Janković, Drina and Vranješ-Đurić, Sanja",
year = "2021",
abstract = "Small glucose-modified liposomes (GMLs) were loaded with magnetic Fe3O4 nanoparticles (MNPs) and fluorescein using a standard thin layer preparation procedure and a varying lipid/MNPs ratio. The liposomes were characterized with TEM and DLS measurements, and MNPs encapsulation rate was determined using ICP-OES. Prepared liposomes were stored at 5 °C for 30 days and subsequently exposed to an external magnetic field (20 mT) with varying exposure times (2‒20 min), at room temperature. The release of fluorescein from GMLs induced by the magnetic field exposures was quantified, showing a high release rate (25‒85%) depending on the concentration of MNPs in GMLs. EPR measurements were conducted during the liposomes storage period in order to provide semi-quantitative information of possible MNPs oxidation from Fe3O4 to Fe2O3 inside the liposomes, impacting MNPs magnetic properties. In contrast to the MNPs water dispersion, no significant change in the EPR signal of MNPs encapsulated inside GMLs was detected over the course of 30 days. The data presented in this study indicate that GMLs loaded with MNPs maintain a high stability for prolonged periods of time and that this delivery system may be used for magnetically assisted controlled drug release.",
journal = "Journal of Nanoparticle Research",
title = "Magnetically induced controlled release from glucose-modified liposomes loaded with Fe3O4 nanoparticles",
volume = "23",
number = "11",
pages = "252",
doi = "10.1007/s11051-021-05375-2"
}

Cvjetinović, Đ., Milanović, Z., Mirković, M. D., Petrović, J., Vesković, A., Popović-Bijelić, A., Prijović, Ž., Janković, D.,& Vranješ-Đurić, S.. (2021). Magnetically induced controlled release from glucose-modified liposomes loaded with Fe3O4 nanoparticles. in Journal of Nanoparticle Research, 23(11), 252.
https://doi.org/10.1007/s11051-021-05375-2

Cvjetinović Đ, Milanović Z, Mirković MD, Petrović J, Vesković A, Popović-Bijelić A, Prijović Ž, Janković D, Vranješ-Đurić S. Magnetically induced controlled release from glucose-modified liposomes loaded with Fe3O4 nanoparticles. in Journal of Nanoparticle Research. 2021;23(11):252.
doi:10.1007/s11051-021-05375-2 .

Cvjetinović, Đorđe, Milanović, Zorana, Mirković, Marija D., Petrović, Jelena, Vesković, Ana, Popović-Bijelić, Ana, Prijović, Željko, Janković, Drina, Vranješ-Đurić, Sanja, "Magnetically induced controlled release from glucose-modified liposomes loaded with Fe3O4 nanoparticles" in Journal of Nanoparticle Research, 23, no. 11 (2021):252,
https://doi.org/10.1007/s11051-021-05375-2 . .

TY  - JOUR
AU  - Cvjetinović, Đorđe
AU  - Janković, Drina
AU  - Milanović, Zorana
AU  - Mirković, Marija D.
AU  - Petrović, Jelena
AU  - Prijović, Željko
AU  - Poghosyan, Emiliya
AU  - Vranješ-Đurić, Sanja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9946
AB  - Micro–sized multivesicular liposomes were prepared, radiolabeled with 177Lu, and tested in vitro and in vivo to evaluate the potential of 177Lu–labeled micro liposomes in radiosynoviorthesis (RSO) therapy. A standard reverse–phase procedure of liposome preparation with a lipid mixture of DPPC: CHOL (80:20%) was used for the synthesis. TEM and fluorescence microscopy imaging were performed to determine the size, shape, and structure of the prepared liposomes. Both measurements are in good agreement while TEM micrographs additionally indicate to a large multivesicular inner structure of prepared liposomes. A simple and straightforward procedure was used for liposome radiolabeling with 177Lu, a well–known and commonly used radionuclide in radiotherapy with favorable properties, that can be exploited in RSO therapy. Radiolabeled 177Lu–liposomes were tested in vitro for stability and then injected into the knee joints of Wistar rats where liposome in vivo behavior was followed up to 30 days post injection. Results from both ex vivo biodistribution and in vivo imaging studies presented a high stability and retention (>94 %ID) of 177Lu–micro liposomes in the synovial liquid for the entire observation period. Leakage of free 177Lu or 177Lu–liposomes from the synovial fluid has not been detected, indicating to a possible application of 177Lu–liposomes in radiosynoviorthesis (RSO) therapy.
T2  - International Journal of Pharmaceutics
T2  - International Journal of PharmaceuticsInternational Journal of Pharmaceutics
T1  - 177Lu–labeled micro liposomes as a potential radiosynoviorthesis therapeutic agent
VL  - 608
SP  - 121106
DO  - 10.1016/j.ijpharm.2021.121106
ER  - 

@article{
author = "Cvjetinović, Đorđe and Janković, Drina and Milanović, Zorana and Mirković, Marija D. and Petrović, Jelena and Prijović, Željko and Poghosyan, Emiliya and Vranješ-Đurić, Sanja",
year = "2021",
abstract = "Micro–sized multivesicular liposomes were prepared, radiolabeled with 177Lu, and tested in vitro and in vivo to evaluate the potential of 177Lu–labeled micro liposomes in radiosynoviorthesis (RSO) therapy. A standard reverse–phase procedure of liposome preparation with a lipid mixture of DPPC: CHOL (80:20%) was used for the synthesis. TEM and fluorescence microscopy imaging were performed to determine the size, shape, and structure of the prepared liposomes. Both measurements are in good agreement while TEM micrographs additionally indicate to a large multivesicular inner structure of prepared liposomes. A simple and straightforward procedure was used for liposome radiolabeling with 177Lu, a well–known and commonly used radionuclide in radiotherapy with favorable properties, that can be exploited in RSO therapy. Radiolabeled 177Lu–liposomes were tested in vitro for stability and then injected into the knee joints of Wistar rats where liposome in vivo behavior was followed up to 30 days post injection. Results from both ex vivo biodistribution and in vivo imaging studies presented a high stability and retention (>94 %ID) of 177Lu–micro liposomes in the synovial liquid for the entire observation period. Leakage of free 177Lu or 177Lu–liposomes from the synovial fluid has not been detected, indicating to a possible application of 177Lu–liposomes in radiosynoviorthesis (RSO) therapy.",
journal = "International Journal of Pharmaceutics, International Journal of PharmaceuticsInternational Journal of Pharmaceutics",
title = "177Lu–labeled micro liposomes as a potential radiosynoviorthesis therapeutic agent",
volume = "608",
pages = "121106",
doi = "10.1016/j.ijpharm.2021.121106"
}

Cvjetinović, Đ., Janković, D., Milanović, Z., Mirković, M. D., Petrović, J., Prijović, Ž., Poghosyan, E.,& Vranješ-Đurić, S.. (2021). 177Lu–labeled micro liposomes as a potential radiosynoviorthesis therapeutic agent. in International Journal of Pharmaceutics, 608, 121106.
https://doi.org/10.1016/j.ijpharm.2021.121106

Cvjetinović Đ, Janković D, Milanović Z, Mirković MD, Petrović J, Prijović Ž, Poghosyan E, Vranješ-Đurić S. 177Lu–labeled micro liposomes as a potential radiosynoviorthesis therapeutic agent. in International Journal of Pharmaceutics. 2021;608:121106.
doi:10.1016/j.ijpharm.2021.121106 .

Cvjetinović, Đorđe, Janković, Drina, Milanović, Zorana, Mirković, Marija D., Petrović, Jelena, Prijović, Željko, Poghosyan, Emiliya, Vranješ-Đurić, Sanja, "177Lu–labeled micro liposomes as a potential radiosynoviorthesis therapeutic agent" in International Journal of Pharmaceutics, 608 (2021):121106,
https://doi.org/10.1016/j.ijpharm.2021.121106 . .

TY  - JOUR
AU  - Cvjetinović, Đorđe
AU  - Prijović, Željko
AU  - Janković, Drina
AU  - Radović, Magdalena
AU  - Mirković, Marija D.
AU  - Milanović, Zorana
AU  - Mojović, Miloš
AU  - Škalamera, Đani
AU  - Vranješ-Đurić, Sanja
PY  - 2021
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/9151
AB  - Liposomes are promising drug's delivery systems due to decreased toxicity of the liposome-encapsulated drug, but wider clinical application requires their more efficient tumor targeting with uptake, controlled drug release and higher shelf life. The unique metabolic characteristics of cancer cells based on higher demand for energy and therefore increased glucose utilization were exploited in the design of glucose modified liposomes (GML) with the aim to provide increased tumor targeting via glucose transporters and increased ability of drug delivery into tumor cells. Tumor accumulating potential of GML and non-glucose liposomes (NGL) were investigated on CT26 and LS174T tumor-bearing mice by simple and reliable radiotracer method using 177Lu as radioactive marker. Both liposomes, GML and NGL were radiolabeled in high radiolabeling yield, showing high in vitro stability in biological media, as the main prerequisite for the biodistribution studies. Tumors displayed significantly better accumulation of 177Lu-GML with the maximum uptake 6 h post-injection (5.8 ± 0.2%/g in LS174T tumor and 5.1 ± 0.5%/g in CT26 tumor), compared to negligible uptake of 177Lu-NGL (0.6 ± 0.1%/g in LS174T tumor and 0.9 ± 0.2%/g in CT26 tumor). Results of comparative biodistribution studies of 177Lu-NGL and 177Lu-GML indicate that increased accumulation of GML is enabled by glucose transporters and subsequent endocytosis, resulting in their prolonged retention in tumor tissues (up to 72 h). Direct radiolabeling of liposomes with 177Lu may be used not only for biodistribution studies using radiotracking, but also for cancer treatment. © 2021 Elsevier B.V.
T2  - Journal of Controlled Release
T1  - Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking
VL  - 332
SP  - 301
EP  - 311
DO  - 10.1016/j.jconrel.2021.03.006
ER  - 

@article{
author = "Cvjetinović, Đorđe and Prijović, Željko and Janković, Drina and Radović, Magdalena and Mirković, Marija D. and Milanović, Zorana and Mojović, Miloš and Škalamera, Đani and Vranješ-Đurić, Sanja",
year = "2021",
abstract = "Liposomes are promising drug's delivery systems due to decreased toxicity of the liposome-encapsulated drug, but wider clinical application requires their more efficient tumor targeting with uptake, controlled drug release and higher shelf life. The unique metabolic characteristics of cancer cells based on higher demand for energy and therefore increased glucose utilization were exploited in the design of glucose modified liposomes (GML) with the aim to provide increased tumor targeting via glucose transporters and increased ability of drug delivery into tumor cells. Tumor accumulating potential of GML and non-glucose liposomes (NGL) were investigated on CT26 and LS174T tumor-bearing mice by simple and reliable radiotracer method using 177Lu as radioactive marker. Both liposomes, GML and NGL were radiolabeled in high radiolabeling yield, showing high in vitro stability in biological media, as the main prerequisite for the biodistribution studies. Tumors displayed significantly better accumulation of 177Lu-GML with the maximum uptake 6 h post-injection (5.8 ± 0.2%/g in LS174T tumor and 5.1 ± 0.5%/g in CT26 tumor), compared to negligible uptake of 177Lu-NGL (0.6 ± 0.1%/g in LS174T tumor and 0.9 ± 0.2%/g in CT26 tumor). Results of comparative biodistribution studies of 177Lu-NGL and 177Lu-GML indicate that increased accumulation of GML is enabled by glucose transporters and subsequent endocytosis, resulting in their prolonged retention in tumor tissues (up to 72 h). Direct radiolabeling of liposomes with 177Lu may be used not only for biodistribution studies using radiotracking, but also for cancer treatment. © 2021 Elsevier B.V.",
journal = "Journal of Controlled Release",
title = "Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking",
volume = "332",
pages = "301-311",
doi = "10.1016/j.jconrel.2021.03.006"
}

Cvjetinović, Đ., Prijović, Ž., Janković, D., Radović, M., Mirković, M. D., Milanović, Z., Mojović, M., Škalamera, Đ.,& Vranješ-Đurić, S.. (2021). Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking. in Journal of Controlled Release, 332, 301-311.
https://doi.org/10.1016/j.jconrel.2021.03.006

Cvjetinović Đ, Prijović Ž, Janković D, Radović M, Mirković MD, Milanović Z, Mojović M, Škalamera Đ, Vranješ-Đurić S. Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking. in Journal of Controlled Release. 2021;332:301-311.
doi:10.1016/j.jconrel.2021.03.006 .

Cvjetinović, Đorđe, Prijović, Željko, Janković, Drina, Radović, Magdalena, Mirković, Marija D., Milanović, Zorana, Mojović, Miloš, Škalamera, Đani, Vranješ-Đurić, Sanja, "Bioevaluation of glucose-modified liposomes as a potential drug delivery system for cancer treatment using 177-Lu radiotracking" in Journal of Controlled Release, 332 (2021):301-311,
https://doi.org/10.1016/j.jconrel.2021.03.006 . .