Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor
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2016
Authors
Ignjatović, Nenad L.Penov-Gaši, Katarina
Wu, Victoria
Ajduković, Jovana
Kojić, Vesna V.
Vasiljević-Radović, Dana
Kuzmanović, Maja D.
Uskoković, Vuk
Uskoković, Dragan
Article (Published version)
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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 7.47wt.%. The release of A from HAp/Ch-PLGA was s...ustained, 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=168nm. 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.
Keywords:
Androstane / Chitosan / Hydroxyapatite / Nanoparticle / PLGASource:
Colloids and Surfaces. B: Biointerfaces, 2016, 148, 629-639Publisher:
- Elsevier
Funding / projects:
- Molecular designing of nanoparticles with controlled morphological and physicochemical characteristics and functional materials based on them (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-45004)
- Synthesis, characterization and biological investigation of steroid derivatives and their molecular aggregates (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
WoS: 000388248500073
Scopus: 2-s2.0-84989184184
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VinčaTY - JOUR AU - Ignjatović, Nenad L. AU - Penov-Gaši, Katarina AU - Wu, Victoria AU - Ajduković, Jovana AU - Kojić, Vesna V. AU - Vasiljević-Radović, Dana AU - Kuzmanović, Maja D. AU - Uskoković, Vuk AU - Uskoković, Dragan PY - 2016 UR - http://dais.sanu.ac.rs/123456789/15974 UR - https://vinar.vin.bg.ac.rs/handle/123456789/7569 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 7.47wt.%. 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=168nm. 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 L. and Penov-Gaši, Katarina and Wu, Victoria and Ajduković, Jovana and Kojić, Vesna V. and Vasiljević-Radović, Dana and Kuzmanović, Maja D. 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 7.47wt.%. 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=168nm. 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. L., Penov-Gaši, K., Wu, V., Ajduković, J., Kojić, V. V., Vasiljević-Radović, D., Kuzmanović, M. D., 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 Elsevier., 148, 629-639. https://doi.org/10.1016/j.colsurfb.2016.09.041
Ignjatović NL, Penov-Gaši K, Wu V, Ajduković J, Kojić VV, Vasiljević-Radović D, Kuzmanović MD, 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 .
Ignjatović, Nenad L., Penov-Gaši, Katarina, Wu, Victoria, Ajduković, Jovana, Kojić, Vesna V., Vasiljević-Radović, Dana, Kuzmanović, Maja D., 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 . .