Comb-like PEG-containing polymeric composition as low toxic drug nanocarrier

Lesya Kobylinska,Igor Patereha,Natalia Finiuk,Alexander Zaichenko,Natalia Mitina,Rostyslav Stoika,Igor Kotsyumbas,Anna Riabtseva,Sandor G Vari

doi:10.1186/s12645-018-0045-5

Abstract

BackgroundDevelopment of biocompatible multifunctional polymeric drug carriers is crucial in modern pharmaceutics aimed to create “smart” drugs. The high potential of the PEGylated comb-like polymeric nanocarrier (PNC) in delivering both traditional and experimental drugs to tumor cells in vitro and in vivo has been demonstrated previously. In the present study, we investigated the general toxicity of polyethylene glycol (PEG) processed with both covalent and non-covalent attachments of PEG to compose a comb-like polymer that behaves like a simple chain of n monomers decorated with swollen side chains. The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone.ResultsWe have demonstrated that the synthesized PNC possesses weak toxic effects toward human leukemia cells (HL-60 and Jurkat lines), as well as toward hepatocellular (HepG2), colon (HCT116) and breast (MCF-7) tumor cell lines. Additionally, after a long period (20 days) of intraperitoneal administration, the PNC had no significant toxic effects in laboratory white mice (470 mg/kg body mass in 1 ml) and Wistar rats (440 mg/kg body mass in 10 ml).ConclusionThe developed PNC we studied can be qualified as a compound of grade 4 toxicity (low toxicity substance). The reduced toxicity of this PNC in combination with its improved bioavailability and previously detected capability to enhance cytotoxicity toward tumor cells in vitro and potential tumor treatment effects in vivo suggests its potential as a safe drug delivery platform for treating various diseases, especially cancer.

Highlights

In the last two decades, lipid and polymer-based nanocarriers have been studied as alternative drug delivery systems that can enhance the solubility of drugs by encapsulating existing and new anticancer drugs (Feng et al 2015; Zhang et al 2009)
In this study, we demonstrated that the synthesized comb-like polyethylene glycol (PEG)-containing polymeric nanocarrier (PNC) possesses weak toxic effects toward human leukemia cells (HL-60 and Jurkat lines), as well as toward hepatocellular (HepG2), colon (HCT116), and breast (MCF-7) tumor cell lines
The PNC has no toxic effect in laboratory white mice and laboratory Wistar rats

Summary

Introduction

In the last two decades, lipid and polymer-based nanocarriers have been studied as alternative drug delivery systems that can enhance the solubility of drugs by encapsulating existing and new anticancer drugs (Feng et al 2015; Zhang et al 2009). Nanocarriers provide additional advantages for tumor treatment since the conjugate of the anticancer drug with different carriers may reduce systemic toxicity and enhance drug accumulation in malignant tissue (Feng et al 2015; Zhang et al 2009). In these ways, nanocarrierbased drug delivery will improve the efficacy of anticancer chemotherapy (Wang et al 2017). The PNC possesses properties of a water-soluble surfactant containing methyl-terminated PEG side branches in some monomer units attached covalently to the carbon chain backbone

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