Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
Аутори
Ignjatović, NenadPenov Gaši, Katarina
Wu, Victoria
Ajduković, Jovana
Kojić, Vesna
Vasiljević Radović, Dana
Kuzmanović, Maja
Uskoković, Vuk
Uskoković, Dragan
Чланак у часопису (Рецензирана верзија)
Метаподаци
Приказ свих података о документуАпстракт
In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was ...sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.
Кључне речи:
androstane / chitosan / hydroxyapatite / lung cancer / PLGAИзвор:
Colloids and Surfaces B: Biointerfaces, 2016, 148, 629-639Финансирање / пројекти:
- Молекуларно дизајнирање наночестица контролисаних морфолошких и физичко-хемијских карактеристика и функционалних материјала на њиховој основи (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-45004)
- Синтеза, карактеризација и биолошка испитивања стероидних деривата и њихових молекулских агрегата (RS-MESTD-Basic Research (BR or ON)-172021)
- United States National Institutes of Health (NIH) / National Institute of Dental and Craniofacial Research (NIDCR), Grant K99-DE021416
Напомена:
- This is the peer-reviewed version of the articleIgnjatović, N.L., Penov-Gaši, K.M., Wu, V.M., Ajduković, J.J., Kojić, V.V., Vasiljević-Radović, D., Kuzmanović, M., Uskoković, V., Uskoković, D.P., 2016. Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. Colloids and Surfaces B: Biointerfaces 148, 629–639. https://doi.org/10.1016/j.colsurfb.2016.09.041
DOI: 10.1016/j.colsurfb.2016.09.041
ISSN: 0927-7765 (Print); 1873-4367
PubMed: 27694053
WoS: 000388248500073
Scopus: 2-s2.0-84989184184
Институција/група
Институт техничких наука САНУ / Institute of Technical Sciences of SASATY - JOUR AU - Ignjatović, Nenad AU - Penov Gaši, Katarina AU - Wu, Victoria AU - Ajduković, Jovana AU - Kojić, Vesna AU - Vasiljević Radović, Dana AU - Kuzmanović, Maja AU - Uskoković, Vuk AU - Uskoković, Dragan PY - 2016 UR - https://dais.sanu.ac.rs/123456789/15984 AB - In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells. T2 - Colloids and Surfaces B: Biointerfaces T1 - Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor SP - 629 EP - 639 VL - 148 DO - 10.1016/j.colsurfb.2016.09.041 UR - https://hdl.handle.net/21.15107/rcub_dais_15984 ER -
@article{ author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna and Vasiljević Radović, Dana and Kuzmanović, Maja and Uskoković, Vuk and Uskoković, Dragan", year = "2016", abstract = "In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. 1H NMR and 13C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the thermal degradation products and properties of A-loaded HAp/Ch-PLGA. The loading efficiency, as indicated by the comparison of enthalpies of phase transitions in pure A and A-loaded HAp/Ch-PLGA, equaled 7.47 wt.%. The release of A from HAp/Ch-PLGA was sustained, neither exhibiting a burst release nor plateauing after three weeks. Atomic force microscopy and particle size distribution analyses were used to confirm that the particles were spherical with a uniform size distribution of d50 = 168 nm. In vitro cytotoxicity testing of A-loaded HAp/Ch-PLGA using MTT and trypan blue dye exclusion assays demonstrated that the particles were cytotoxic to the A549 human lung carcinoma cell line (46 ± 2%), while simultaneously preserving high viability (83 ± 3%) of regular MRC5 human lung fibroblasts and causing no harm to primary mouse lung fibroblasts. In conclusion, composite A-loaded HAp/Ch-PLGA particles could be seen as promising drug delivery platforms for selective cancer therapies, targeting malignant cells for destruction, while having a significantly lesser cytotoxic effect on the healthy cells.", journal = "Colloids and Surfaces B: Biointerfaces", title = "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor", pages = "629-639", volume = "148", doi = "10.1016/j.colsurfb.2016.09.041", url = "https://hdl.handle.net/21.15107/rcub_dais_15984" }
Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, J., Kojić, V., Vasiljević Radović, D., Kuzmanović, M., Uskoković, V.,& Uskoković, D.. (2016). Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces, 148, 629-639. https://doi.org/10.1016/j.colsurfb.2016.09.041 https://hdl.handle.net/21.15107/rcub_dais_15984
Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić V, Vasiljević Radović D, Kuzmanović M, Uskoković V, Uskoković D. Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor. in Colloids and Surfaces B: Biointerfaces. 2016;148:629-639. doi:10.1016/j.colsurfb.2016.09.041 https://hdl.handle.net/21.15107/rcub_dais_15984 .
Ignjatović, Nenad, Penov Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna, Vasiljević Radović, Dana, Kuzmanović, Maja, Uskoković, Vuk, Uskoković, Dragan, "Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor" in Colloids and Surfaces B: Biointerfaces, 148 (2016):629-639, https://doi.org/10.1016/j.colsurfb.2016.09.041 ., https://hdl.handle.net/21.15107/rcub_dais_15984 .