Biological In Vitro Evaluation of PIL Graft Conjugates: Cytotoxicity Characteristics

Abstract

In vitro cytotoxicity of polymer-carriers, which in the side chains contain the cholinum ionic liquid units with chloride (Cl) or pharmaceutical anions dedicated for antituberculosis therapy, i.e., p-aminosalicylate (PAS) and clavulanate (CLV), was investigated. The carriers and drug conjugates were examined, in the concentration range of 3.125–100 μg/mL, against human bronchial epithelial cells (BEAS-2B) and adenocarcinomic human alveolar basal epithelial cells (A549) as an experimental model cancer cell line possibly coexisting in tuberculosis. The cytotoxicity was evaluated by MTT test and confluency index, as well as by the cytometric analyses, including Annexin-V FITC apoptosis assay. The polymer systems showed supporting activity towards the normal cells and no tumor progress, especially at the highest concentration (100 μg/mL). The analysis of cell death did not show meaningful changes in the case of the BEAS-2B, whereas in the A549 cell line, the cytostatic activity was observed, especially for the drug-free carriers, causing death in up to 80% of cells. This can be regulated by the polymer structure, including the content of cationic units, side-chain length and density, as well as the type and content of pharmaceutical anions. The results of MTT tests, confluency, as well as cytometric analyses, distinguished the polymer systems with Cl/PAS/CLV containing 26% of grafting degree and 43% of ionic units or 46% of grafting degree and 18% of ionic units as the optimal systems.

Pharmaceutical Functionalization of Monomeric Ionic Liquid for the Preparation of Ionic Graft Polymer Conjugates

“…In general, cytotoxicity decreased with lowering concentrations of polymer. However, it can be seen that at a higher concentration (100 µg/mL) the cells’ proliferation was slightly improved in the presence of FUS¯ compared to 25–50 µg/mL due to cell adaptation [ 39 ], whereas in front of CLX¯, it was nearly at the same level. Moreover, after 72h of incubation, the confluence, which is a percentage of covered surface by the cells, was evaluated for untreated control cells and conjugate samples at concentrations 100 µg/mL and 3 µg/mL ( Figure 6 ).…”

Dual-Drug Delivery via the Self-Assembled Conjugates of Choline-Functionalized Graft Copolymers

“…Cytotoxicity tests indicated the non-toxic action of IL-graft copolymers against normal BEAS-2B cell lines. Moreover, their selective biological action was observed versus normal and lung cancer cell lines [21]. Furthermore, the ionic structure of IL units was convenient for the ionic exchange reaction, which in this study, was used to introduce fusidate anions (FUS − ) into the side chains of the copolymer.…”

“…The most important properties of DDSs are the high biocompatibility and low toxicity of many ILs, which can improve the pharmacokinetic and pharmacodynamic properties of the drugs being transported [15][16][17]. Some of them, i.e., cholinium-based ILs, show biological functions [18][19][20][21]. Micelles based on IL (co)polymers have been studied for the encapsulation and delivery of various active pharmaceutical ingredients (APIs), e.g., erythromycin, indomethacin, quercetin [22], curcumin [23,24], acyclovir [25], paclitaxel [26], dopamine [27], and doxorubicin [28,29].…”

Pixantrone Sensitizes Gram-Negative Pathogens to Rifampin

“…Annexin V-FITC (5 μL) and PI (5 μL) were added to the suspension. After incubating at room temperature for 15 min in the dark, the stained cells were analyzed by flow cytometry ( 71 ).…”