Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved Properties as an Anticancer Agent

Abstract

This study aims to improve the cytotoxicity and potency of cisplatin-loaded polybutylcyanoacrylate (PBCA) nanoparticles (NPs) for the treatment of lung cancer through the modulation of temperature and polyethylene glycol (PEG) concentration as effective factors affecting the NPs’ properties. The NPs were synthesized using an anionic polymerization method and were characterized in terms of size, drug loading efficiency, drug release profile, cytotoxicity effects, drug efficacy, and drug side effects. In this regard, dynamic light scattering (DLS), scanning electron microscopy (SEM), 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) methods, and hematoxylin and eosin (H&E) staining were used. The results showed that the size and the drug loading efficiency of the synthesized spherical NPs were 355–386 nm and 14–19%, respectively. Also, the drug release profile showed a controlled and slow drug release pattern with approximately 10% drug release over 48 h. In addition, the NPs significantly increased the cytotoxicity of the cisplatin in vitro environment by approximately 2 times and enhanced the therapeutic effects of the drug in vivo environment by increasing the survival time of lung-cancer-bearing mice by 20% compared to the standard drug receiver group. Also, the nanoformulation decreased the drug toxicity in an in vivo environment. According to the results, increasing the temperature and PEG concentration improved the properties of the drug loading efficiency, drug release profile, and cytotoxicity effect of drug-loaded NPs. Consequently, the synthesized formulation increased the survival of tumor-bearing mice and simultaneously decreased the cisplatin toxicity effects. In conclusion, the prepared nanoformulation can be considered a promising candidate for further evaluation for possible therapeutic use in the treatment of lung cancer.

Enhanced Efficacy of PEGylated Liposomal Cisplatin: In Vitro and In Vivo Evaluation

“…Also, the results of the present study showed that the tumor number was significantly decreased in tumor-bearing rats receiving PLCispt compared to other groups (the tumor numbers in control, PBS, Cispt, LCispt, and PLCispt groups were 21.8 ± 1.1, 20 ± 0.9, 12.1 ± 0.6, 8.1 ± 0.4, and 5.3 ± 0.2, respectively). Moreover, tumor growth inhibition index (TGII) was measured to confirm the anticancer effects of the formulations [33], which was 4%, 59%, 78%, and 91% in PBS, Cispt, LCispt, and PLCispt groups, respectively, confirming the higher anticancer effects of PLCispt compared to the other formulations. To evaluate the toxicity effects of the formulations, changes in the bodyweight of animals and in the serum concentrations of kidney-and liver-related factors were measured, including blood urea nitrogen (BUN), creatinine, aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) [55]; and histopathological studies were performed.…”

“…All nanoformulations had negative zeta potentials, resulting in them having proper stability in aqueous solutions with low ionic strength. This finding results from the fact that particles with the same charge (negative or positive) repulse each other [33], and this prevents aggregation. However, the zeta potential of LCispt was more positive than that of liposome due to the positive charge of Cispt [33].…”

“…This finding results from the fact that particles with the same charge (negative or positive) repulse each other [33], and this prevents aggregation. However, the zeta potential of LCispt was more positive than that of liposome due to the positive charge of Cispt [33]. Also, PEGylation caused an increase in the zeta potentials of liposomes due to the surface coating of nanoparticles by PEG chains [34,35].…”

Development and Characterization of Nanoliposomal Hydroxyurea Against BT-474 Breast Cancer Cells

“…The OD was monitored using ELISA reader at 570 nm. Cell viability percentage and IC 50 (50% inhibitory concentration of cell growth in comparison to untreated control cells as negative control), 22,23 were determined. All tests were done in triplicate.…”

Preparation, Characterization, and Evaluation of Cisplatin-Loaded Polybutylcyanoacrylate Nanoparticles with Improved In Vitro and In Vivo Anticancer Activities

“…Nanoparticles have been widely investigated as drug delivery systems to increase the therapeutic efficacy of drugs [12][13][14][15][16] and reduce their side effects [17,18]. Nanoparticles have a high surface area to volume ratio; therefore, they could encapsulate drugs in high concentrations and increase drug delivery to cancerous cells [19].…”