The effect of the androstane lung cancer inhibitor content on the cell-selective toxicity of hydroxyapatite-chitosan-PLGA nanocomposites

Abstract

An androstane (17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (derivative A)) cancer inhibitor was successfully captured in a carrier made of nano-sized hydroxyapatite (HAp) coated with chitosan-PLGA polymer blends (Ch-PLGA). In our previous studies, we demonstrated that it was convenient to use spherical HAp/Ch-PLGA carriers as vehicles to target the lungs following intravenous administration. In this study, we used emulsification and subsequent freeze-drying to load the spherical HAp/Ch-PLGA carriers with varying contents of the derivative A, in order to examine the selective toxicity towards cancerous/healthy lung cells. The XRD and FT-IR techniques confirmed the drug loading process, and the content of the poorly water soluble derivative A was estimated directly via the DSC technique. The particles were spherical in shape with the d distribution varying between 167 and 231 nm, whereas the content of the derivative A ranged from 6.5 to 19.3 wt%. Cell-selective cytotoxicity was examined simultaneously on two cell lines: human lung carcinoma (A549 ATCC CCL 185) and human lung fibroblasts (MRC-5 ATCC CCL 171). All particles exhibited nearly three times larger cytotoxicity towards cancer cells (A549) than towards healthy cells (MRC5), where the particles with the derivative A content of 6.5 wt% allowed for the viability of healthy cells >80%. Ninety-six hours after the treatment of cells with particles with different contents of derivative A (after incubation and recovery), recovery was faster in damaged healthy cells than in cancerous cells.

Chitosan nanobeads loaded with Biginelli hybrids as cell-selective toxicity systems with a homogeneous distribution of the cell cycle in cancer treatment

“…All bands are also found in the chitosan spectra reported by others. 19,28 The appearance of bands characteristic for pure Biginelli derivatives A, B and C in the spectra of the A-Ch and B-Ch and C-Ch systems may be indicative of Biginelli pyrimidines entrapped in Ch during the synthesis of NPs. Furthermore, an increased intensity of the C-H band near 3200 cm À1 in the spectra of the A-Ch, B-Ch and C-Ch systems as compared to the spectra of pure A, B and C, respectively, is probably due to hydrogen bonding between A, B and C Biginelli derivatives and Ch.…”

“…There are numerous examples demonstrating how different technological operations can change the effects of active pharmaceutical ingredients in appropriate drugs. [18][19][20] In Fig. 4 SEM micrographs of (a) A-Ch, (b) B-Ch, and (c) C-Ch.…”

“…[14][15][16][17] Our previous research, highlights that anticancer drugs based on anticancer compounds loaded into nanoparticles of bioresorbable polymers have improved features. [18][19][20] With an improved understanding of nanomaterials and the application of nanotechnology our strategies are currently being directed towards improving the ability of anticancer nanostructures to target specic tissues and to reduce the toxicity of pure compounds by coating them with appropriate nanocarriers. According to SciFinder®, in July 2020, more than 70 000 different Biginelli-like compounds have been published.…”

Nanoparticles in the Use of Natural Products for the Treatment of Lung Cancer

“…Hydroxyapatite is an inorganic bone component widely used in bone tissue reconstruction, and more recent studies have found that hydroxyapatite nanoparticles have selective anticancer activity for lung cancer cells. Ignjatovic et al (38) demonstrate that it is possible to develop hydroxyapatite nanoparticle with chitosan and poly-lactic-co-glycolic (PLGA) to make them more selective for the A549 lung cancer cell line than for healthy cells. Chen et al (39) also makes use of nanoparticles of hydroxyapatite in the delivery of ionizing radiation for the treatment of lung cancer, obtaining positive results and proposing a new alternative for the treatment of lung cancer.…”

From molecules to nanoparticles to functional materials

“…%) were designed and their potential for activity toward lung cancer cells examined. 21 As the content of derivative A increased, so did the median value of the particle size distribution, with the particles containing 7.5, 11.2 and 15 wt.% A having the d 50 values of 167, 168 and 231 nm, respectively. The cancer cell targeting potential of the particles was examined simultaneously on human lung cancer cells (A549) and human lung fibroblasts (MRC5) using the dye exclusion assay (DET) and the colorimetric test with the tetrazolium salt (MTT).…”