Abstract
This paper presents the modification of the antibiotic rifampicin by an anionic polyelectrolyte using a simplified electrochemically mediated atom transfer radical polymerization (seATRP) technique to receive stimuli-responsive polymer materials. Initially, a supramolecular ATRP initiator was prepared by an esterification reaction of rifampicin hydroxyl groups with α-bromoisobutyryl bromide (BriBBr). The structure of the initiator was successfully proved by nuclear magnetic resonance (1H and 13C NMR), Fourier-transform infrared (FT-IR) and ultraviolet–visible (UV-vis) spectroscopy. The prepared rifampicin-based macroinitiator was electrochemically investigated among various ATRP catalytic complexes, by a series of cyclic voltammetry (CV) measurements, determining the rate constants of electrochemical catalytic (EC’) process. Macromolecules with rifampicin core and hydrophobic poly (n-butyl acrylate) (PnBA) and poly(tert-butyl acrylate) (PtBA) side chains were synthesized in a controlled manner, receiving polymers with narrow molecular weight distribution (Mw/Mn = 1.29 and 1.58, respectively). “Smart” polymer materials sensitive to pH changes were provided by transformation of tBA into acrylic acid (AA) moieties in a facile route by acidic hydrolysis. The pH-dependent behavior of prepared macromolecules was investigated by dynamic light scattering (DLS) determining a hydrodynamic radius of polymers upon pH changes, followed by a control release of quercetin as a model active substance upon pH changes.
Highlights
Polymers as multifunctional structures are intensively studied in drug formulation and drug delivery systems [1,2,3,4]
The use of CuII Br2 /Tris (2-pyridylmethyl)amine (TPMA)*2 provided a synthesis of more controlled linear structure comparing to CuII Br2 /TPMA ligand [58], substituted with electron-donating groups pyridine ligand is too active for the preparation of architecture macromolecules presented in this paper, losing control during synthesis, resulting in coupling reactions, and in high dispersity and a higher theoretical dead chain fraction value (DCFtheo = 0.26 vs. 0.12, compare DCFtheo, Supplementary Table S3, entries 1 and 2)
The supramolecular initiator was prepared by an esterification reaction of rifampicin and bromoisobutyryl bromide (BriBBr), receiving atom transfer radical polymerization (ATRP) macroinitiator with three bromide initiation sites, proved by 1 H NMR analysis, Fourier-transform infrared (FT-IR) spectrum
Summary
Polymers as multifunctional structures are intensively studied in drug formulation and drug delivery systems [1,2,3,4] It is directly connected with unique properties of polymers to respond to external stimuli, i.e., thermoresponsive macromolecules, such as a widely known poly(N-isopropylacrylamide) [5] or recently studied poly(2-isopropenyl-2-oxazoline) [6], and polyelectrolytes with positively or negatively charged groups, sensitive to pH changes, e.g., anionic poly(acrylic acid) (PAA) [7] or cationic poly(2-(dimethylamino)ethyl methacrylate) [8], making them “smart” materials and promising candidates to control encapsulate and release of drugs, and cell-specific targeting [1,9,10]. There is a wide range of nontoxic, biocompatible, and biodegradable polymeric materials, successfully implemented in the controlled release of different substances upon pH changes. This subject is especially privileged among antibiotics delivery systems. Direct modification of drugs by an appropriate polymer provides additional benefits beyond the possibility for extended-release delivery systems, namely, improves the property of drugs [12] and can avoid the resistance of antibiotics for bacteria [13]
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