Katarzyna Krukiewicz

Biomaterial-based regional chemotherapy: Local anticancer drug delivery to enhance chemotherapy and minimize its side-effects

Since the majority of anticancer pharmacological agents affect not only cancer tissue but also normal cells, chemotherapy is usually accompanied with severe side effects. Regional chemotherapy, as the alternative version of conventional treatment, leads to the enhancement of the therapeutic efficiency of anticancer drugs and, simultaneously, reduction of toxic effects to healthy tissues. This paper provides an insight into different approaches of local delivery of chemotherapeutics, such as the injection of anticancer agents directly into tumor tissue, the use of injectable in situ forming drug carriers or injectable platforms in a form of implants. The wide range of biomaterials used as reservoirs of anticancer drugs is described, i.e. poly(ethylene glycol) and its copolymers, polyurethanes, poly(lactic acid) and its copolymers, poly(ɛ-caprolactone), polyanhydrides, chitosan, cellulose, cyclodextrins, silk, conducting polymers, modified titanium surfaces, calcium phosphate based biomaterials, silicone and silica implants, as well as carbon nanotubes and graphene. To emphasize the applicability of regional chemotherapy in cancer treatment, the commercially available products approved by the relevant health agencies are presented.

Advancing the delivery of anticancer drugs: Conjugated polymer/triterpenoid composite.

Exemplifying the synergy of anticancer properties of triterpenoids and ion retention qualities of conjugated polymers, we propose a conducting matrix to be a reservoir of anticancer compounds. In this study, poly(3,4-ethylenedioxythiophene), PEDOT, based matrix for electrically triggered and local delivery of the ionic form of anticancer drug, oleanolic acid (HOL), has been investigated. An initial, one-step fabrication procedure has been proposed, providing layers exhibiting good drug release properties and biological activity. Investigation of obtained systems and implementation of modifications revealed another route of fabrication. This procedure was found to yield layers possessing a significantly greater storage capacity of OL(-), as evidenced by the 52% increase in the drug concentrations attainable through electro-assisted release. Examination of the biological activity of immobilised and released OL(-) molecules proved that electrochemical treatment has negligible impact on the anticancer properties of OL(-), particularly when employing the three-step procedure, in which the range of applied potentials is limited. PEDOT/OL(-) composite has been demonstrated to be a robust and cost-effective material for controlled drug delivery.

An electrically controlled drug delivery system based on conducting poly(3,4-ethylenedioxypyrrole) matrix.

As numerous therapeutic agents are not well tolerated when administrated systemically, localized and controlled delivery can help to decrease their toxicity by applying an optimized drug concentration at extended exposure time. Among different types of drug delivery systems, conjugated polymers are considered as promising materials due to their biocompatibility, electrical conductivity and ability to undergo controllable redox reactions. In this work poly(3,4-ethylenedioxypyrrole), PEDOP, matrix is described for the first time as a reservoir of a model drug, ibuprofen (IBU). Drug immobilization process is performed in situ, during the electrochemical polymerization of 10 mM EDOP in the presence of 5-50 mM IBU. The loading efficiency of polymer matrix is dependent on IBU concentration and reaches 25.0±1.3 μg/cm2. The analysis of PEDOP-IBU chemical structure based on Raman spectroscopy, energy dispersive spectroscopy and surface morphology data provided by scanning electron microscopy shows that IBU is accumulated in the structure of matrix and evidently influences its morphology. IBU is then released in a controlled way under the influence of applied potential (-0.7 V vs. Ag/AgCl). It is demonstrated that the judicious choice of the synthesis conditions leads to a tailored loading efficiency of PEDOP matrix and to a tunable drug release.

Electrical percolation in composites of conducting polymers and dielectrics

Abstract This article deals with the electrical conductivity of a composite of two polymers, one of which is a conducting polymer, whereas the second is a dielectric. The problem was formulated within the framework of electrical percolation, i.e., the percolation thresholds, which allow for a high electrical conductivity, is under investigation. For this purpose, a numerical model was developed, and its parameters were analyzed and discussed. Based on the determined thresholds, it was possible to evaluate the weight ratios of the conducting-dielectric polymers in a composite. The proposed approach allows for reducing the manufacturing cost of composite material with respect to conducting polymers with simultaneous retaining of high conductance properties of conducting polymers, as well as durability and flexibility of dielectrics.

Two approaches to the model drug immobilization into conjugated polymer matrix

The purpose of this study is to develop biocompatible and conducting coating being carrier of biologically active compounds with the potential use in neuroprosthetics. Conducting polypyrrole matrix has been used to immobilize and release model drugs, quercetin and ciprofloxacin. Two routes of immobilization are described: drugs have been incorporated in the polymer matrix in the course of the electropolymerization process or after polymerization, in the course of polymer oxidation. Using UV/Vis spectroscopic detection we demonstrate that both immobilization approaches display different drug-loading efficiencies. In the case of ciprofloxacin, drug incorporation following synthesis is a more efficient immobilization approach (final drug concentration: 43.3 (±9.5) μM/cm(2)), while for quercetin the highest loading is accomplished by drug incorporation during synthesis (final drug concentration: 29.1 (±5.9) μM/cm(2)). The process of drug incorporation results in the variation of surface morphology with respect to the method of immobilization as well as the choice of drug. The results prove that electrochemical methods are efficient procedures for making multifunctional polymer matrices which might be perspective bioactive coatings for implantable neuroprosthetic devices.

Betulin-loaded PEDOT films for regional chemotherapy

Chemotherapy is one of the most commonly used cancer treatments. Even so, it has significant adverse effects on healthy tissues. These effects can be avoided through the use of regional chemotherapy, an approach based on delivering the anti-cancer agents locally, to the site of cancer tissue accumulation. Among the different classes of biomaterials that are used as drug carriers, conducting polymers allow reversible, electrostatic immobilization and controlled release of a variety of compounds. In this work, we describe a method for producing surfaces possessing anti-cancer activity, which are a potential tool for regional chemotherapy. Our method consists of covering the surface with a conducting polymer matrix, followed by loading that matrix with cytotoxic compounds. We have chosen betulin as the model compound for this study, as it is commonly available triterpene that exhibits cytotoxicity against a variety of tumor cell lines. The presence of betulin in the polymer matrix is confirmed by SEM, EDS and IR spectroscopy. The release of betulin is carried out using two protocols, i.e. passive mode (open circuit conditions) or active (application of constant potential) mode. The biological activity of betulin that was released from the matrix is confirmed by its toxic effect against KB and MCF-7 cancer cell lines (IC50 values of 13.34±0.88μg/mL and 12.57±1.81μg/mL for KB and MCF-7, respectively). The described method of surface modification is shown to be an effective mean of producing surfaces that possess anti-cancer activity, serving as advantageous materials for regional chemotherapy applications.

Concept of a Conducting Composite Material for Lightning Strike Protection

Abstract The paper focuses on development of a multifunctional material which allows conducting of electrical current and simultaneously holds mechanical properties of a polymeric composite. Such material could be applied for exterior fuselage elements of an aircraft in order to minimize damage occurring during lightning strikes. The concept introduced in this paper is presented from the points of view of various scientific disciplines including materials science, chemistry, structural physics and mechanical engineering with a discussion on results achieved to-date and further plans of research.

Synthesis and testing of a conducting polymeric composite material for lightning strike protection applications

Lightning strike protection is one of the important issues in the modern maintenance problems of aircraft. This is due to a fact that the most of exterior elements of modern aircraft is manufactured from polymeric composites which are characterized by isolating electrical properties, and thus cannot carry the giant electrical charge when the lightning strikes. This causes serious damage of an aircraft structure and necessity of repairs and tests before returning a vehicle to operation. In order to overcome this problem, usually metallic meshes are immersed in the polymeric elements. This approach is quite effective, but increases a mass of an aircraft and significantly complicates the manufacturing process. The approach proposed by the authors is based on a mixture of conducting and dielectric polymers. Numerous modeling studies which are based on percolation clustering using kinetic Monte Carlo methods, finite element modeling of electrical and mechanical properties, and preliminary experimental studies,...

Electrically conductive carbon fibre-reinforced composite for aircraft lightning strike protection

Aircraft elements, especially elements of exterior fuselage, are subjected to damage caused by lightning strikes. Due to the fact that these elements are manufactured from polymeric composites in modern aircraft, and thus, they cannot conduct electrical charges, the lightning strikes cause burnouts in composite structures. Therefore, the effective lightning strike protection for such structures is highly desired. The solution presented in this paper is based on application of organic conductive fillers in the form of intrinsically conducting polymers and carbon fabric in order to ensure electrical conductivity of whole composite and simultaneously retain superior mechanical properties. The presented studies cover synthesis and manufacturing of the electrically conductive composite as well as its characterization with respect to mechanical and electrical properties. The performed studies indicate that the proposed material can be potentially considered as a constructional material for aircraft industry, which characterizes by good operational properties and low cost of manufacturing with respect to current lightning strike protection materials solutions.

The influence of oxygen conditioning effect on the permeation properties of polyaniline membranes

ABSTRACT The effect of oxygen conditioning on the performance of polyaniline (PANI) membranes is presented and discussed. The presence of the conditioning effect in such kind of polymer matrix was confirmed by measuring a variation in spin concentration using electron paramagnetic resonance (EPR) spectroscopy. The observed decrease in spin concentration indicates the presence of the dissolved oxygen incompletely removed from PANI matrix. After the prolonged contact between oxygen and PANI membrane, a pronounced decrease in membrane’s selectivity was observed, which may be explained by the firm and permanent interaction between oxygen molecules and nitrogen paramagnetic centers of PANI and could be considered as a kind of PANI irreversible doping process.