Selective anticancer activity of hydroxyapatite/chitosan-poly(D,L)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
Autori
Ignjatović, NenadPenov Gaši, Katarina
Wu, Victoria
Ajduković, Jovana
Kojić, Vesna V.
Vasiljević-Radović, Dana
Kuzmanović, Maja
Uskoković, Vuk
Uskoković, Dragan P.
Članak u časopisu (Recenzirana verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
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.
Ključne reči:
androstane / chitosan / hydroxyapatite / lung cancer / PLGAIzvor:
Colloids and Surfaces B: Biointerfaces, 2016, 148, 629-639Finansiranje / projekti:
- Molekularno dizajniranje nanočestica kontrolisanih morfoloških i fizičko-hemijskih karakteristika i funkcionalnih materijala na njihovoj osnovi (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-45004)
- Sinteza, karakterizacija i biološka ispitivanja steroidnih derivata i njihovih molekulskih agregata (RS-MESTD-Basic Research (BR or ON)-172021)
- United States National Institutes of Health (NIH), Grant R00-DE021416
Napomena:
- 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 (Online)
PubMed: 27694053
WoS: 000388248500073
Scopus: 2-s2.0-84989184184
Institucija/grupa
IHTMTY - JOUR AU - Ignjatović, Nenad AU - Penov Gaši, Katarina AU - Wu, Victoria AU - Ajduković, Jovana AU - Kojić, Vesna V. AU - Vasiljević-Radović, Dana AU - Kuzmanović, Maja AU - Uskoković, Vuk AU - Uskoković, Dragan P. PY - 2016 UR - http://dais.sanu.ac.rs/123456789/15984 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2644 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 VL - 148 SP - 629 EP - 639 DO - 10.1016/j.colsurfb.2016.09.041 ER -
@article{ author = "Ignjatović, Nenad and Penov Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna V. and Vasiljević-Radović, Dana and Kuzmanović, Maja and Uskoković, 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 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", volume = "148", pages = "629-639", doi = "10.1016/j.colsurfb.2016.09.041" }
Ignjatović, N., Penov Gaši, K., Wu, V., Ajduković, 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. in Colloids and Surfaces B: Biointerfaces, 148, 629-639. https://doi.org/10.1016/j.colsurfb.2016.09.041
Ignjatović N, Penov Gaši K, Wu V, Ajduković J, Kojić VV, Vasiljević-Radović D, Kuzmanović M, Uskoković 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 Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna V., Vasiljević-Radović, Dana, Kuzmanović, Maja, Uskoković, 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 . .