Selective anticancer activity of hydroxyapatite/chitosan-poly(d,l)-lactide-co-glycolide particles loaded with an androstane-based cancer inhibitor.
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 and13C 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.
Institute of Technical Sciences of the Serbian Academy of Science and Arts, Knez Mihailova 35/IV, P.O. Box 377, 11000 Belgrade, Serbia.
Nenad L
NL
Ignjatović
University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
Katarina M
KM
Penov-Gaši
Advanced Materials and Nanobiotechnology Laboratory, Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, 9401 Jeronimo Road, Irvine, CA 92618-1908, USA.
Victoria M
VM
Wu
University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental Protection, Trg Dositeja Obradovića 3, 21000 Novi Sad, Serbia.
Jovana J
JJ
Ajduković
University of Novi Sad, Faculty of Medicine, Oncology Institute of Vojvodina, Dr Goldmana 4, 21204 Sremska Kamenica, Serbia.
Vesna V
VV
Kojić
University of Belgrade, Institute for Chemistry, Technology and Metallurgy, Njegoševa 12, Belgrade, Serbia.
Dana
D
Vasiljević-Radović
Institute of Technical Sciences of the Serbian Academy of Science and Arts, Knez Mihailova 35/IV, P.O. Box 377, 11000 Belgrade, Serbia.
Maja
M
Kuzmanović
Advanced Materials and Nanobiotechnology Laboratory, Department of Biomedical and Pharmaceutical Sciences, School of Pharmacy, Chapman University, 9401 Jeronimo Road, Irvine, CA 92618-1908, USA; Department of Bioengineering, University of Illinois, 851 South Morgan Street, Chicago, IL 60607-7052, USA. Electronic address: uskokovi@chapman.edu.
Vuk
V
Uskoković
Institute of Technical Sciences of the Serbian Academy of Science and Arts, Knez Mihailova 35/IV, P.O. Box 377, 11000 Belgrade, Serbia. Electronic address: dragan.uskokovic@itn.sanu.ac.rs.
Dragan P
DP
Uskoković
D000072283:A549 Cells; D000731:Androstanes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D065546:Drug Liberation; D017886:Durapatite / Q000737:chemistry*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019344:Lactic Acid / Q000737:chemistry*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008810:Mice, Inbred C57BL; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000737:chemistry; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D017550:Spectroscopy, Fourier Transform Infrared; D013818:Thermogravimetry
D000731:Androstanes; D000970:Antineoplastic Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D017886:Durapatite; C033936:androstane
Androstane; Chitosan; Hydroxyapatite; Lung cancer; Nanoparticle; PLGA
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