Abstract
Different types of amphiphilic macromolecular structures have been developed within recent decades to prepare the polymer particles considered as drug delivery systems. In the present research the series of amphiphilic block-copolymers containing poly(glutamatic acid) as hydrophilic, and polyphenylalanine as hydrophobic blocks was synthesized and characterized. Molecular weights for homo- and copolymers were determined by gel-permeation chromatography (GPC) and amino acid analysis, respectively. The copolymers obtained were applied for preparation of polymer particles. The specific morphology of prepared polymerosomes was proved using transmission electron microscopy (TEM). The influence on particle size of polymer concentration and pH used for self-assembly, as well as on the length of hydrophobic and hydrophilic blocks of applied copolymers, was studied by dynamic light scattering (DLS). Depending on different experimental conditions, the formation of nanoparticles with sizes from 60 to 350 nm was observed. The surface of polymersomes was modified with model protein (enzyme). No loss in biocatalytic activity was detected. Additionally, the process of encapsulation of model dyes was developed and the possibility of intracellular delivery of the dye-loaded nanoparticles was proved. Thus, the nanoparticles discussed can be considered for the creation of modern drug delivery systems.
Highlights
The development of modern drug delivery systems to solve the problem of directed transport at cellular and sub-cellular scales reduces both the probability of loaded drug degradation and its high toxicity in the body [1]
Materials γ-benzyl-L-glutamate, L-phenylalanine, triphosgene, α-pinene, n-hexylamine (HEXA), trifluoromethanesulfonic acid (TFMSA), trifluoroacetic acid (TFA), N-hydroxysuccinimide (NHS), 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide (CDI), bromophenol blue, rhodamine 6g, 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT), and other reagents were purchased from Sigma-Aldrich (Darmstadt, Germany) and used as received. 1,4-dioxane, n-hexane, N,Ndimethylformamide (DMF), dimethyl sulfoxide (DMSO), ethyl acetate, methanol, and other solvents were purchased from Vecton Ltd
As1.aAs firsta step, synthesis of TheThe general scheme presented in Figure first the step, the synthesis several homopolymers of γ-Glu(Bzl) was carried out using the method of ring-opening polymerization of several homopolymers of γ-Glu(Bzl) was carried out using the method of ring-opening of the corresponding polymerization of the corresponding
Summary
The development of modern drug delivery systems to solve the problem of directed transport at cellular and sub-cellular scales reduces both the probability of loaded drug degradation and its high toxicity in the body [1]. Elevated attention has been paid to the polymer nanovesicles of a core-shell structure with double layer liposome-like membranes [5,6,7,8]. The structure of such a polymer shell has much in common with that of a cell membrane, which can enhance the cell permeability for developed nanoparticles. These nanocarriers, composed of the amphiphilic block-copolymers, are known under the name polymersomes and, compared to liposomes, demonstrate higher membrane stability
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