Marcin Mackiewicz

Stable and degradable microgels linked with cystine for storing and environmentally triggered release of drugs

Environmentally sensitive, degradable microgels based on poly(N-isopropylacrylamide) (pNIPA) cross-linked with the diacryloyl derivative of cystine (BISS) were synthesized by applying surfactant-free emulsion polymerization. pNIPA contributed the sensitivity to temperature to the microgels and the cross-linker made them degradable and sensitive to pH. The morphology of the microgels was investigated by using scanning and transmission electron microscopies (SEM and TEM). The gels formed spherical particles with a narrow size distribution. The influence of temperature, pH and ionic strength on the swelling behavior and the stability of new microgels with various contents of BISS (0, 1 and 3%) were investigated by dynamic light scattering (DLS). It was found that microgels with 3% content of amino acid were highly stable over a wide range of investigated temperatures, pH values and ionic strengths, including the physiological conditions (pH = 7.4, IS = 0.15 M, and 37 °C). The reduction-induced degradation of these microgels by 0.01 M solution of dithiothreitol (DTT) or glutathione (GSH) was studied by means of SEM and TEM; the obtained micrographs showed the destruction of spherical microgel particles. The microgels containing 3% of BISS could be loaded with doxorubicin (DOX) by employing the electrostatic interactions between the DOX amine group and the ionized carboxyl group from BISS. A significant increase in the cumulative release of DOX was observed after changing pH from that characteristic to blood (∼7.4) to that existing in affected cells (∼5.0) and in the presence of GSH (CGSH∼ 10 mM). The cytotoxicity tests proved that the obtained microgels are interesting as useful carriers in directed drug delivery systems.

Environmentally sensitive, quickly responding microgels with lattice channels filled with polyaniline

A conducting microcomposite composed of cross-linked poly(N-isopropylacrylamide) (pNIPA) and polyaniline (PANI) was synthesized. First, pNIPA gel microcapsules were prepared via surfactant-free emulsion polymerization (SFEP). Then by soaking the gel with a solution of an oxidizing agent (sodium persulfate) and placing it in a solution of aniline in nitrobenzene the conducting polymer was formed in pNIPA. The structure, morphology, swelling behavior and polyaniline oxidation state in the composite were investigated using SEM, TEM, DLS and Raman spectroscopy. The new microcomposite consists of micro-spheres, undergoes rapid volume phase transition and is electroactive. A result of the transition from the swollen to the collapsed state is a strong enhancement of the voltammetric peaks of polyaniline.

New ampholytic microgels based on N-isopropylacrylamide and α-amino acid: changes in swelling behavior as a function of temperature, pH and divalent cation concentration

Several new microgels based on N-isopropylacrylamide and the amino acid L-ornithine were synthesized by means of surfactant free emulsion polymerization. N-δ-Acryloyl ornithine was copolymerized with N-isopropylacrylamide and N,N′-methylenebisacrylamide, leading to the synthesis of a new ampholytic microgel. The swelling behavior of the obtained microgels with respect to the amount of amino acid incorporated in the polymer network, temperature, concentration of ions and pH was investigated. The pH dependence of the microgel size, measured at a constant temperature, was found to exhibit a minimum; the pH range where the minimum appeared corresponded well with the pH range where zwitterions dominated. The temperature dependence of the swelling process obtained for different pH values showed that for the pH region where zwitterions dominated, the polymer networks collapsed more efficiently. The presence of free α-amino acid groups attached to the polymeric network of the microgels also enabled the complexation of some metal cations. The influence of the presence of two metal ions (Cu2+ and Ca2+), which differ significantly in their ability to form complexes with the α-amino-acid, on the swelling behavior was investigated. It was found that the presence of copper ions that form stable complexes with the α-amino acid strongly influenced the swelling behavior of the investigated microgels.

Voltammetric and electrochemical gravimetric selective detection of interactions between Tl(I) and guanine and the influence on activity of DNA drug-intercalators

The interactions of Tl(I), a well known toxic species, with selected oligonucleotides were examined. The oligonucleotide sequences selected for the investigation were taken from gene hOGG1 responsible for repairing of DNA damage. Cyclic voltammetry was particularly useful, since nitrogen N-7 in guanine can be electrooxidized while its binding with Tl(I) leads to the loss of electroactivity. So, this selected interaction could be quantitatively used in drawing Scatchards plot and calculating the binding constants and the number of active sites in guanine molecules occupied by one metal ion. Further, we have shown that the presence of Tl(I) leads to a decrease in activity of doxorubicin (DOX), a popular anticancer drug, vs. DNA. The obtained circular dichroism (CD) spectra and the measurements with an electrochemical quartz crystal microbalance (EQCM) led to a conclusion that in the presence of monovalent thallium cations the DNA double helix was neither damaged/oxidized nor its conformation changed substantially.

An environmentally sensitive three-component hybrid microgel

A new multifunctional microcomposite has been synthesized. It is sensitive to several medium parameters, such as temperature, pH and ionic strength, is electroactive and conductive and can be easily attached to gold surfaces. All these properties were cumulated in one microcomposite by combining three components: poly(N-isopropylacrylamide) crosslinked with N,N′-bisacryloylcystine (p(NIPA–BISS) microgel), polyaniline nanofibers and gold nanoparticles. The presence of the polyaniline nanofibers and gold nanoparticles in the composite particles led to a substantial increase in conductivity and electroactivity. Additionally, the transition from the swollen to the collapsed state further enhanced the electroactivity and conductivity of the microcomposite. The structure, morphology and swelling behavior of the microgels were investigated using SEM, TEM, TGA, DLS and Raman spectroscopy. The electrocatalytic properties of the microcomposite towards oxidation of ethanol were also found.

A degradable nanogel drug carrier crosslinked with three-oligonucleotide hybrids for two-way drug release in mild and high hyperthermia treatment

Three-segment oligonucleotide hybrids were introduced as crosslinkers to a PNIPA-AAc nanonetwork. The obtained nanogels could be specifically transformed and degraded. The specific architecture of the presented carrier aims at achieving effective cancer treatment with reduced side toxicity. As a result, compared to the gels with regular crosslinkers, the drug release could be independently realized by (a) changing the structure of the gel net and conformation of DNA hybrids in an oscillating way and (b) degradation of DNA crosslinkers by denaturation. The hydrodynamic diameter and zeta potential of the nanogels were examined as a function of T and pH. The presence of a DNA helix in the nanogels led to a substantial increase, of nearly three times, in the storing efficiency of the selected anticancer drug compared to the nanogels with regular crosslinkers. Moreover, the nanogels allowed 98% drug release efficiency at high hyperthermic and 70% at mild hyperthermic conditions. The effectiveness of cytotoxicity of insulinoma cells was better compared to free doxorubicin. Since in the proposed approach, in addition to the drug, the third DNA strand can be also liberated, this opens new possibilities in development of gene therapies. This novel biocompatible carrier exhibits enhanced drug loading, possesses tunable and degradable properties under hyperthermic conditions and offers controlled release of the drug.