Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
Само за регистроване кориснике
2016
Аутори
Ignjatović, NenadPenov-Gasi, Katarina M.
Wu, Victoria M.
Ajduković, Jovana J.
Kojić, Vesna V.
Vasiljević-Radović, Dana
Kuzmanovic, Maja
Uskokovicć, Vuk
Uskoković, Dragan P.
Чланак у часопису (Објављена 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 17 beta-hydroxy-17 alpha-picolyl-androst-5-en-3 beta-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. H-1 NMR and C-13 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 H...Ap/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 d(50) = 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 / Nanoparticle / PLGAИзвор:
Colloids and Surfaces B-Biointerfaces, 2016, 148, 629-639Издавач:
- Elsevier
Финансирање / 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 - R00-DE021416
DOI: 10.1016/j.colsurfb.2016.09.041
ISSN: 0927-7765
PubMed: 27694053
WoS: 000388248500073
Scopus: 2-s2.0-84989184184
Институција/група
IHTMTY - JOUR AU - Ignjatović, Nenad AU - Penov-Gasi, Katarina M. AU - Wu, Victoria M. AU - Ajduković, Jovana J. AU - Kojić, Vesna V. AU - Vasiljević-Radović, Dana AU - Kuzmanovic, Maja AU - Uskokovicć, Vuk AU - Uskoković, Dragan P. PY - 2016 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/1996 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 17 beta-hydroxy-17 alpha-picolyl-androst-5-en-3 beta-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. H-1 NMR and C-13 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 d(50) = 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. PB - Elsevier 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 VL - 148 SP - 629 EP - 639 DO - 10.1016/j.colsurfb.2016.09.041 ER -
@article{ author = "Ignjatović, Nenad and Penov-Gasi, Katarina M. and Wu, Victoria M. and Ajduković, Jovana J. and Kojić, Vesna V. and Vasiljević-Radović, Dana and Kuzmanovic, Maja and Uskokovicć, Vuk and Uskoković, Dragan P.", 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 17 beta-hydroxy-17 alpha-picolyl-androst-5-en-3 beta-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. H-1 NMR and C-13 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 d(50) = 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.", publisher = "Elsevier", 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", volume = "148", pages = "629-639", doi = "10.1016/j.colsurfb.2016.09.041" }
Ignjatović, N., Penov-Gasi, K. M., Wu, V. M., Ajduković, J. J., Kojić, V. V., Vasiljević-Radović, D., Kuzmanovic, M., Uskokovicć, 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. in Colloids and Surfaces B-Biointerfaces Elsevier., 148, 629-639. https://doi.org/10.1016/j.colsurfb.2016.09.041
Ignjatović N, Penov-Gasi KM, Wu VM, Ajduković JJ, Kojić VV, Vasiljević-Radović D, Kuzmanovic M, Uskokovicć V, Uskoković DP. 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 .
Ignjatović, Nenad, Penov-Gasi, Katarina M., Wu, Victoria M., Ajduković, Jovana J., Kojić, Vesna V., Vasiljević-Radović, Dana, Kuzmanovic, Maja, Uskokovicć, Vuk, Uskoković, Dragan P., "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 . .