Amino-üre Grubu ile Fonksiyonelleştirilmiş Yeni Bir Nanotaşıyıcının Sentezi, Karakterizasyonu ve İlaç Salım Özelliklerinin İncelenmesi
Yıl 2024,
Cilt: 24 Sayı: 5, 1094 - 1101, 01.10.2024
Amelya Gök
,
Süleyman Akif Demirel
,
Emine Özkan
,
Osman Tayyar Arlı
Öz
Kurkumin, anti-kanser özelliklerine sahip yaygın bir doğal üründür, ancak düşük çözünürlüğü, vücuttaki etki yerine ulaşma hızının yavaş olması ve kararsızlığı nedeniyle kanser araştırmalarındaki kullanımı sınırlıdır. Kurkuminin kanser tedavisindeki kullanımında karşılaşılan sorunların üstesinden gelmek ve tedavi süresince etkinliğini artırmak amacıyla ilaç taşıyıcı sistemlerin kullanılması çözüm olarak ortaya çıkmıştır. Yapılan bu çalışmada, ilk olarak silika taşıyıcılar arasında en yaygın olan MCM-41 malzemesi hazırlanmıştır. Daha sonra MCM-41 malzemesinin üre-amin grubu ile türevlendirilmesi sonrası MCM-41-AG malzemesi elde edilmiştir. Hazırlanan bu silika taşıyıcı sistemler kullanılarak kurkumin yükleme ve salım çalışmaları gerçekleştirilmiştir. Kurkumin yüklemesi, silika taşıyıcılar ile kurkumin çözeltisinin 24 saat karanlıkta karıştırılması ile gerçekleştirilmiştir. Bu işlem sonrası, kurkumin@MCM-41 ve kurkumin@MCM-41-AG olarak adlandırılan kurkumin yüklü malzemeler elde edilmiştir. Yapılan ölçümlerden kurkumin yükleme yüzdesi, MCM-41 için %14 ve türevlendirilmiş MCM-41-AG için %16,7 olarak hesaplanmıştır. Kurkumin@MCM-41 ve kurkumin@MCM-41-AG malzemelerinden pH 5.5 ve pH 7.4’de kurkumin salımı çalışılmıştır. Yapılan ölçümler sonrası, kurkumin@MCM-41’in her iki pH değerinde de taşıdığı kurkuminin %90’nını ilk 15 dakika içinde bıraktığı belirlenmiştir. Kurkumin@MCM-41-AG taşıdığı kurkuminin pH 5.5’de %31’ni 75 dakika içinde ve pH 7.4’de %39’nu 60 dakika içinde bıraktığı belirlenmiştir. Elde edilen bu sonuçlar, türevlendirilmiş silika taşıyıcı MCM-41-AG’in çıplak MCM-41’e kıyasla daha fazla kurkumin taşıyabildiği ve taşıdığı kurkumini daha az oranda ve daha uzun sürede kontrollü olarak bırakabildiğini göstermektedir.
Etik Beyan
Yazarlar tüm etik standartlara uyduklarını beyan ederler.
Teşekkür
AG, SAD ve EÖ, bu çalışma sırasında laboratuvar imkanlarını kullanmalarına izin veren Burdur Mehmet Akif Ersoy Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü’ne ve çalışmalar sırasında desteğini esirgemeyen Burdur Ayşe Sak Ortaokulu idarecilerine ve öğretmenlerine teşekkür eder.
Kaynakça
- AbouAitah, K. E. A., Farghali, A. A., Swiderska-Sroda, A., Lojkowski, W., Razin, A. and Khedr, M. K., 2016. pH-controlled release system for curcumin based on functionalized dendritic mesoporous silica nanoparticles. J Nanomed Nanotechnol, 7(1), 351.
https://doi.org/10.4172/2157-7439.1000351
- Adahoun, M. A. A., Al-Akhras, M. A. H., Jaafar, M. S. and Bououdina, M., 2017. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles. Artif Cells Nanomed Biotechnol, 45(1), 98-107.
https://doi.org/10.3109/21691401.2015.1129628
- Ahmadi Nasab, N., Hassani Kumleh, H., Beygzadeh, M., Teimourian, S. and Kazemzad, M., 2018. Delivery of curcumin by a pH-responsive chitosan mesoporous silica nanoparticles for cancer treatment. Artif Cells Nanomed Biotechnol, 46(1), 75-81.
https://doi.org/10.1080/21691401.2017.1290648
- Atiyah, N. A., Albayati, T. M. and Atiya, M. A., 2022. Functionalization of mesoporous MCM-41 for the delivery of curcumin as an anti-inflammatory therapy. Adv. Powder Techno, 33(2), 103417.
- Arli, O. T., Gök, Y. and Gök H. Z., 2023. pH responsive curcumin released from urea-amine group functionalized mesoporous organosilica nanoparticles. Turk. J. Chem, 47(6), 1518-1528.
https://doi.org/10.55730/1300-0527.3632
- Armarego, W. L., 2022. Purification of laboratory chemicals: Part 2 inorganic chemicals, catalysts, biochemicals, physiologically active chemicals, nanomaterials. Butterworth-Heinemann.
- Atiyah, N. A., Albayati, T. M. and Atiya, M. A., 2022. Functionalization of mesoporous MCM-41 for the delivery of curcumin as an anti-inflammatory therapy. Adv. Powder Techno, 33(2), 103417.
https://doi.org/10.1016/j.apt.2021.103417
- Atiyah, N. A., Albayati, T. M. and Atiya, M. A., 2022. Interaction behavior of curcumin encapsulated onto functionalized SBA-15 as an efficient carrier and release in drug delivery. J. Mol. Struct, 1260, 132879.
https://doi.org/10.1016/j.molstruc.2022.132879
- Chen, C., Sun, W., Wang, X., Wang, Y. and Wang, P., 2018. Rational design of curcumin loaded multifunctional mesoporous silica nanoparticles to enhance the cytotoxicity for targeted and controlled drug release. Mater. Sci. Eng. C, 85, 88-96.
https://doi.org/10.1016/j.msec.2017.12.007
- Croissant, J. G., Cattoën, X., Man, M. W. C., Durand, J. O. and Khashab, N. M., 2015. Syntheses and applications of periodic mesoporous organosilica nanoparticles. Nanoscale, 7(48), 20318-20334.
https://doi.org/10.1039/C5NR05649G
- Croissant, J. G., Fatieiev, Y. and Khashab, N. M., 2017. Degradability and clearance of silicon, organosilica, silsesquioxane, silica mixed oxide, and mesoporous silica nanoparticles. Adv. Mater, 29(9), 1604634.
https://doi.org/10.1002/adma.201604634
- Croissant, J. G., Fatieiev, Y., Omar, H., Anjum, D. H., Gurinov, A., Lu, J. and Khashab, N. M., 2016. Periodic mesoporous organosilica nanoparticles with controlled morphologies and high drug/dye loadings for multicargo delivery in cancer cells. Chem. Eur. J., 22(28), 9607-9615.
https://doi.org/10.1002/chem.201600587
- Devassy, J. G., Nwachukwu, I. D. and Jones, P. J., 2015. Curcumin and cancer: barriers to obtaining a health claim. Nutr. Rev, 73(3), 155-165.
https://doi.org/10.1093/nutrit/nuu064
- De Oliveira, L. F., Bouchmella, K., Goncalves, K. D. A., Bettini, J., Kobarg, J. and Cardoso, M. B., 2016. Functionalized silica nanoparticles as an alternative platform for targeted drug-delivery of water insoluble drugs. Langmuir, 32(13), 3217-3225.
https://doi.org/10.1021/acs.langmuir.6b00214
- Diab, R., Canilho, N., Pavel, I. A., Haffner, F. B., Girardon, M. and Pasc, A., 2017. Silica-based systems for oral delivery of drugs, macromolecules and cells. dv. Colloid Interface Sci, 249, 346-362.
https://doi.org/10.1016/j.cis.2017.04.005
- Elbialy, N. S., Aboushoushah, S. F., Sofi, B. F. and Noorwali, A., 2020. Multifunctional curcumin-loaded mesoporous silica nanoparticles for cancer chemoprevention and therapy. Microporous Mesoporous Mater, 291, 109540.
https://doi.org/10.1016/j.micromeso.2019.06.002
- Giordano, A. and Tommonaro, G., 2019. Curcumin and cancer. Nutrients, 11(10), 2376.
https://doi.org/10.3390/nu11102376
- Gök, Y. and Gök, H. Z., 2024. Preparation of mesoporous silica and organosilica nanostructures functionalized with C2‐symmetric diol and their catalytic performance in diethylzinc addition to aromatic aldehydes. Appl. Organomet. Chem, 38(3), e7359.
https://doi.org/10.1002/aoc.7359
- Gök, Y., Aykut, I. T. and Gök, H. Z., 2020. Readily accessible mesoporous silica nanoparticles supported chiral urea‐amine bifunctional catalysts for enantioselective reactions. Appl. Organomet. Chem, 34(12), e6015.
https://doi.org/10.1002/aoc.6015
- Gök, Y., Arlı, O. T., Gök, H. Z. and Türkaslan, T, 2023. Rational synthesis of pH-responsive mesoporous organosilica nanoparticles functionalized with 2-aminothiophenol for controlled release of curcumin. J. Porous Mater, 30(6), 1887-1896.
https://doi.org/10.1007/s10934-023-01472-w
- Gök, Y., Arlı, O. T. and Gök, H. Z., 2022. Trans-stilbene based spherical mesoporous organosilica material for loading and release of hydrophobic curcumin. Turk. J. Health Sci. Life, 5(3), 214-221.
https://10.56150/tjhsl.1201671
- Gupta, S. C., Sung, B., Kim, J. H., Prasad, S., Li, S. and Aggarwal, B. B., 2013. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Mol. Nutr. Food Res, 57(9), 1510-1528.
https://doi.org/10.1002/mnfr.201100741
- Hartono, S. B., Hadisoewignyo, L., Yang, Y., Meka, A. K. and Yu, C., 2016. Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement. Nanotechnology, 27(50), 505605.
https://doi.org/10.1088/0957-4484/27/50/505605
- Hatcher, H., Planalp, R., Cho, J., Torti, F. M. and Torti, S. V., 2008. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci, 65, 1631-1652.
https://doi.org/10.1007/s00018-008-7452-4
- Liu, Y., Ding, X., Li, J., Luo, Z., Hu, Y., Liu, J. and Cai, K., 2015. Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo. Nanotechnology, 26(14), 145102.
https://doi.org/10.1088/0957-4484/26/14/145102
- Liu, W., Zhu, Y., Wang, F., Li, X., Liu, X., Pang, J. and Pan, W., 2018. Galactosylated chitosan-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery. Molecules, 5(12), 181027.
https://doi.org/10.3390/molecules23123082
- Maleki Dizaj, S., Sharifi, S., Tavakoli, F., Hussain, Y., Forouhandeh, H., Hosseiniyan Khatibi, S. M. and Ming, L. C., 2022. Curcumin-Loaded silica nanoparticles: Applications in infectious disease and food industry. Nanomaterials, 12(16), 2848.
https://doi.org/10.3390/nano12162848
- Noureddine, A. and Brinker, C. J., 2018. Pendant/bridged/mesoporous silsesquioxane nanoparticles: Versatile and biocompatible platforms for smart delivery of therapeutics. Chem Eng J, 340, 125-147.
https://doi.org/10.1016/j.cej.2018.01.086
- Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M. and Xia, Y., 2014. Engineered nanoparticles for drug delivery in cancer therapy. Angew. Chem. Int. Ed, 10, 12320-12364.
https://doi.org/10.1002/anie.201403036
- Taebnia, N., Morshedi, D., Yaghmaei, S., Aliakbari, F., Rahimi, F. and Arpanaei, A., 2016. Curcumin-loaded amine-functionalized mesoporous silica nanoparticles inhibit α-synuclein fibrillation and reduce its cytotoxicity-associated effects. Langmuir, 32(50), 13394-13402.
https://doi.org/10.1021/acs.langmuir.6b02935
- Vallet-Regí, M., Colilla, M., Izquierdo-Barba, I. and Manzano, M., 2017. Mesoporous silica nanoparticles for drug delivery: Current insights. Molecules, 23(1), 47.
https://doi.org/10.3390/molecules23010047
- Varache, M., Bezverkhyy, I., Saviot, L., Bouyer, F., Baras, F. and Bouyer, F., 2015. Optimization of MCM-41 type silica nanoparticles for biological applications: Control of size and absence of aggregation and cell cytotoxicity. J. Non-Cryst. Solids, 408, 87-97.
https://doi.org/10.1016/j.jnoncrysol.2014.10.020
- Wang, Y., Zhao, Q., Han, N., Bai, L., Li, J., Liu, J. and Wang, S., 2015. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomed.: Nanotechnol. Biol. Med, 11(2), 313-327.
https://doi.org/10.1016/j.nano.2014.09.014
Synthesis, Characterization and Investigation of Drug Release Properties of A New Nanocarrier Functionalized with Amino-urea Group
Yıl 2024,
Cilt: 24 Sayı: 5, 1094 - 1101, 01.10.2024
Amelya Gök
,
Süleyman Akif Demirel
,
Emine Özkan
,
Osman Tayyar Arlı
Öz
Curcumin is a common natural product with anti-cancer properties, but its use in cancer research is limited due to its low solubility, slow rate of action at the site of action in the body, and instability. The use of drug delivery systems has emerged as a solution to overcome the problems encountered in the use of curcumin in cancer treatment and to increase its effectiveness during treatment. In this study, MCM-41 material, which is the most common among silica carriers, was first prepared. Then, MCM-41-AG material was obtained after derivatization of MCM-41 material with urea-amine group. Curcumin loading and release studies were carried out using these prepared silica carrier systems. Curcumin loading was carried out by mixing silica carriers and curcumin solution in the dark for 24 hours. After this process, curcumin-loaded materials called curcumin@MCM-41 and curcumin@MCM-41-AG were obtained. From the measurements, the curcumin loading percentage was calculated as 14% for MCM-41 and 16.7% for derivatized MCM-41-AG. Curcumin release from curcumin@MCM-41 and curcumin@MCM-41-AG materials was studied at pH 5.5 and pH 7.4. After the measurements, it was determined that 90% of the curcumin carried by curcumin@MCM-41 at both pH values was released within the first 15 minutes. It was determined that the curcumin carried by curcumin@MCM-41-AG released 31% within 75 minutes at pH 5.5 and 39% within 60 minutes at pH 7.4. These results show that the derivatized silica carrier MCM-41-AG can carry more curcumin compared to bare MCM-41 and release the curcumin it carries in a controlled manner at a lower rate and for a longer period of time.
Kaynakça
- AbouAitah, K. E. A., Farghali, A. A., Swiderska-Sroda, A., Lojkowski, W., Razin, A. and Khedr, M. K., 2016. pH-controlled release system for curcumin based on functionalized dendritic mesoporous silica nanoparticles. J Nanomed Nanotechnol, 7(1), 351.
https://doi.org/10.4172/2157-7439.1000351
- Adahoun, M. A. A., Al-Akhras, M. A. H., Jaafar, M. S. and Bououdina, M., 2017. Enhanced anti-cancer and antimicrobial activities of curcumin nanoparticles. Artif Cells Nanomed Biotechnol, 45(1), 98-107.
https://doi.org/10.3109/21691401.2015.1129628
- Ahmadi Nasab, N., Hassani Kumleh, H., Beygzadeh, M., Teimourian, S. and Kazemzad, M., 2018. Delivery of curcumin by a pH-responsive chitosan mesoporous silica nanoparticles for cancer treatment. Artif Cells Nanomed Biotechnol, 46(1), 75-81.
https://doi.org/10.1080/21691401.2017.1290648
- Atiyah, N. A., Albayati, T. M. and Atiya, M. A., 2022. Functionalization of mesoporous MCM-41 for the delivery of curcumin as an anti-inflammatory therapy. Adv. Powder Techno, 33(2), 103417.
- Arli, O. T., Gök, Y. and Gök H. Z., 2023. pH responsive curcumin released from urea-amine group functionalized mesoporous organosilica nanoparticles. Turk. J. Chem, 47(6), 1518-1528.
https://doi.org/10.55730/1300-0527.3632
- Armarego, W. L., 2022. Purification of laboratory chemicals: Part 2 inorganic chemicals, catalysts, biochemicals, physiologically active chemicals, nanomaterials. Butterworth-Heinemann.
- Atiyah, N. A., Albayati, T. M. and Atiya, M. A., 2022. Functionalization of mesoporous MCM-41 for the delivery of curcumin as an anti-inflammatory therapy. Adv. Powder Techno, 33(2), 103417.
https://doi.org/10.1016/j.apt.2021.103417
- Atiyah, N. A., Albayati, T. M. and Atiya, M. A., 2022. Interaction behavior of curcumin encapsulated onto functionalized SBA-15 as an efficient carrier and release in drug delivery. J. Mol. Struct, 1260, 132879.
https://doi.org/10.1016/j.molstruc.2022.132879
- Chen, C., Sun, W., Wang, X., Wang, Y. and Wang, P., 2018. Rational design of curcumin loaded multifunctional mesoporous silica nanoparticles to enhance the cytotoxicity for targeted and controlled drug release. Mater. Sci. Eng. C, 85, 88-96.
https://doi.org/10.1016/j.msec.2017.12.007
- Croissant, J. G., Cattoën, X., Man, M. W. C., Durand, J. O. and Khashab, N. M., 2015. Syntheses and applications of periodic mesoporous organosilica nanoparticles. Nanoscale, 7(48), 20318-20334.
https://doi.org/10.1039/C5NR05649G
- Croissant, J. G., Fatieiev, Y. and Khashab, N. M., 2017. Degradability and clearance of silicon, organosilica, silsesquioxane, silica mixed oxide, and mesoporous silica nanoparticles. Adv. Mater, 29(9), 1604634.
https://doi.org/10.1002/adma.201604634
- Croissant, J. G., Fatieiev, Y., Omar, H., Anjum, D. H., Gurinov, A., Lu, J. and Khashab, N. M., 2016. Periodic mesoporous organosilica nanoparticles with controlled morphologies and high drug/dye loadings for multicargo delivery in cancer cells. Chem. Eur. J., 22(28), 9607-9615.
https://doi.org/10.1002/chem.201600587
- Devassy, J. G., Nwachukwu, I. D. and Jones, P. J., 2015. Curcumin and cancer: barriers to obtaining a health claim. Nutr. Rev, 73(3), 155-165.
https://doi.org/10.1093/nutrit/nuu064
- De Oliveira, L. F., Bouchmella, K., Goncalves, K. D. A., Bettini, J., Kobarg, J. and Cardoso, M. B., 2016. Functionalized silica nanoparticles as an alternative platform for targeted drug-delivery of water insoluble drugs. Langmuir, 32(13), 3217-3225.
https://doi.org/10.1021/acs.langmuir.6b00214
- Diab, R., Canilho, N., Pavel, I. A., Haffner, F. B., Girardon, M. and Pasc, A., 2017. Silica-based systems for oral delivery of drugs, macromolecules and cells. dv. Colloid Interface Sci, 249, 346-362.
https://doi.org/10.1016/j.cis.2017.04.005
- Elbialy, N. S., Aboushoushah, S. F., Sofi, B. F. and Noorwali, A., 2020. Multifunctional curcumin-loaded mesoporous silica nanoparticles for cancer chemoprevention and therapy. Microporous Mesoporous Mater, 291, 109540.
https://doi.org/10.1016/j.micromeso.2019.06.002
- Giordano, A. and Tommonaro, G., 2019. Curcumin and cancer. Nutrients, 11(10), 2376.
https://doi.org/10.3390/nu11102376
- Gök, Y. and Gök, H. Z., 2024. Preparation of mesoporous silica and organosilica nanostructures functionalized with C2‐symmetric diol and their catalytic performance in diethylzinc addition to aromatic aldehydes. Appl. Organomet. Chem, 38(3), e7359.
https://doi.org/10.1002/aoc.7359
- Gök, Y., Aykut, I. T. and Gök, H. Z., 2020. Readily accessible mesoporous silica nanoparticles supported chiral urea‐amine bifunctional catalysts for enantioselective reactions. Appl. Organomet. Chem, 34(12), e6015.
https://doi.org/10.1002/aoc.6015
- Gök, Y., Arlı, O. T., Gök, H. Z. and Türkaslan, T, 2023. Rational synthesis of pH-responsive mesoporous organosilica nanoparticles functionalized with 2-aminothiophenol for controlled release of curcumin. J. Porous Mater, 30(6), 1887-1896.
https://doi.org/10.1007/s10934-023-01472-w
- Gök, Y., Arlı, O. T. and Gök, H. Z., 2022. Trans-stilbene based spherical mesoporous organosilica material for loading and release of hydrophobic curcumin. Turk. J. Health Sci. Life, 5(3), 214-221.
https://10.56150/tjhsl.1201671
- Gupta, S. C., Sung, B., Kim, J. H., Prasad, S., Li, S. and Aggarwal, B. B., 2013. Multitargeting by turmeric, the golden spice: From kitchen to clinic. Mol. Nutr. Food Res, 57(9), 1510-1528.
https://doi.org/10.1002/mnfr.201100741
- Hartono, S. B., Hadisoewignyo, L., Yang, Y., Meka, A. K. and Yu, C., 2016. Amine functionalized cubic mesoporous silica nanoparticles as an oral delivery system for curcumin bioavailability enhancement. Nanotechnology, 27(50), 505605.
https://doi.org/10.1088/0957-4484/27/50/505605
- Hatcher, H., Planalp, R., Cho, J., Torti, F. M. and Torti, S. V., 2008. Curcumin: from ancient medicine to current clinical trials. Cell Mol Life Sci, 65, 1631-1652.
https://doi.org/10.1007/s00018-008-7452-4
- Liu, Y., Ding, X., Li, J., Luo, Z., Hu, Y., Liu, J. and Cai, K., 2015. Enzyme responsive drug delivery system based on mesoporous silica nanoparticles for tumor therapy in vivo. Nanotechnology, 26(14), 145102.
https://doi.org/10.1088/0957-4484/26/14/145102
- Liu, W., Zhu, Y., Wang, F., Li, X., Liu, X., Pang, J. and Pan, W., 2018. Galactosylated chitosan-functionalized mesoporous silica nanoparticles for efficient colon cancer cell-targeted drug delivery. Molecules, 5(12), 181027.
https://doi.org/10.3390/molecules23123082
- Maleki Dizaj, S., Sharifi, S., Tavakoli, F., Hussain, Y., Forouhandeh, H., Hosseiniyan Khatibi, S. M. and Ming, L. C., 2022. Curcumin-Loaded silica nanoparticles: Applications in infectious disease and food industry. Nanomaterials, 12(16), 2848.
https://doi.org/10.3390/nano12162848
- Noureddine, A. and Brinker, C. J., 2018. Pendant/bridged/mesoporous silsesquioxane nanoparticles: Versatile and biocompatible platforms for smart delivery of therapeutics. Chem Eng J, 340, 125-147.
https://doi.org/10.1016/j.cej.2018.01.086
- Sun, T., Zhang, Y. S., Pang, B., Hyun, D. C., Yang, M. and Xia, Y., 2014. Engineered nanoparticles for drug delivery in cancer therapy. Angew. Chem. Int. Ed, 10, 12320-12364.
https://doi.org/10.1002/anie.201403036
- Taebnia, N., Morshedi, D., Yaghmaei, S., Aliakbari, F., Rahimi, F. and Arpanaei, A., 2016. Curcumin-loaded amine-functionalized mesoporous silica nanoparticles inhibit α-synuclein fibrillation and reduce its cytotoxicity-associated effects. Langmuir, 32(50), 13394-13402.
https://doi.org/10.1021/acs.langmuir.6b02935
- Vallet-Regí, M., Colilla, M., Izquierdo-Barba, I. and Manzano, M., 2017. Mesoporous silica nanoparticles for drug delivery: Current insights. Molecules, 23(1), 47.
https://doi.org/10.3390/molecules23010047
- Varache, M., Bezverkhyy, I., Saviot, L., Bouyer, F., Baras, F. and Bouyer, F., 2015. Optimization of MCM-41 type silica nanoparticles for biological applications: Control of size and absence of aggregation and cell cytotoxicity. J. Non-Cryst. Solids, 408, 87-97.
https://doi.org/10.1016/j.jnoncrysol.2014.10.020
- Wang, Y., Zhao, Q., Han, N., Bai, L., Li, J., Liu, J. and Wang, S., 2015. Mesoporous silica nanoparticles in drug delivery and biomedical applications. Nanomed.: Nanotechnol. Biol. Med, 11(2), 313-327.
https://doi.org/10.1016/j.nano.2014.09.014