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

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.

Enhanced Proapoptotic Effects of Water Dispersed Complexes of 4-Thiazolidinone-Based Chemotherapeutics with a PEG-Containing Polymeric Nanocarrier

“…The structures and some characteristics of the PNC are presented in Fig. 2 and were previously described [29].

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Nanocarreadores aplicados ao tratamento do câncer de mama

“…Isto pode ser devido à liberação incompleta do fármaco carregado da formulação, resultando em uma menor eficácia no tratamento. Além disso, estudos anteriores por outros grupos indicaram que o valor de IC50 variou em diferentes linhas de células com o mesmo tratamento Kobylinska (2018) demonstrou a eficiência da liberação de NPs de doxorrubicina, de preparação antitumoral contendo rutênio KP-1019, e de derivados experimentais anticâncer de 4-tiazolidinona, todos voltados para inibir o crescimento e a sobrevivência de células tumorais in vitro e in vivo em ratos e camundongos de laboratório. Akbarzadeh (2021), no Irã, realizou estudos de citotoxicidade in vitro que mostraram alta compatibilidade de AL-NioC (Niossoma-cálcio alginato) com células normais MCF10A, enquanto toxicidade significativa foi observada em células de câncer de mama MDA-MB-231 e SKBR3.…”

Pegylated Curcumin Derivative: Water-Soluble Conjugates with Antitumor and Antibacterial Activity

“…Based on the gathered knowledge, the present study applied direct esterification between Curc and a relatively low-molar mass PEG-diacid (600 g/mol, and PEG 600 -diacid/Curc molar ratio of 1:1 in the starting mixture) in the presence of N , N ′-dicyclohexylcarbodiimide (DCC) to prepare a PEG-Curc conjugate with a specially chosen hydrophilic–hydrophobic balance (curcumin saturation index of about 1 , ), which was expected to ensure (1) higher Curc water solubility, (2) improved stability, and (3) preserved therapeutic index. The presence of Curc in the final product was demonstrated by Fourier transform infrared (FT-IR) spectroscopy analysis.…”