Uroš Maver

Understanding controlled drug release from mesoporous silicates: theory and experiment.

Based on the results of carefully designed experiments upgraded with appropriate theoretical modeling, we present clear evidence that the release curves from mesoporous materials are significantly affected by drug-matrix interactions. In experimental curves, these interactions are manifested as a non-convergence at long times and an inverse dependence of release kinetics on pore size. Neither of these phenomena is expected in non-interacting systems. Although both phenomena have, rather sporadically, been observed in previous research, they have not been explained in terms of a general and consistent theoretical model. The concept is demonstrated on a model drug indomethacin embedded into SBA-15 and MCM-41 porous silicates. The experimental release curves agree exceptionally well with theoretical predictions in the case of significant drug-wall attractions. The latter are described using a 2D Fokker-Planck equation. One could say that the interactions affect the relative cross-section of pores where the local flux has a non-vanishing axial component and in turn control the effective transfer of drug into bulk solution. Finally, we identify the critical parameters determining the pore size dependence of release kinetics and construct a dynamic phase diagram of the various resulting transport regimes.

Novel cellulose based materials for safe and efficient wound treatment.

The present study aims at achieving effects of improved hydrophilicity and microorganism inhibition, which are rarely simultaneously present in wound dressings. Viscose fibers in their non-woven form were modified using two different pathways. Effects of a two-step procedure, i.e. alkaline or oxygen plasma treatment followed by the attachment of silver chloride nanoparticles were compared to a one-step procedure, i.e. ammonium plasma treatment, which results in both desired material characteristics simultaneously. The surface properties of untreated and differently modified cellulose samples were analyzed by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), in vitro silver release, and hydrophilicity measurements. The treatment effect on antimicrobial activity was determined by the AATCC 100-1999 standard test. In light of the introduced wound dressing preparation procedures and the desired wound dressing characteristics, the effectiveness of the used procedures was evaluated. Antimicrobial activity was proven against all Gram negative bacteria, while the Gram positive bacteria survive the as-prepared samples. Hydrophilicity was proven to be excellent using both preparation procedures. The mentioned results prove the potential of the used procedures and encourage future developments toward the clinical proof of concept.

Review of aerogel-based materials in biomedical applications

Due to their many excellent properties, aerogels attract much interest in various applications, ranging from construction to medicine. Over the last decades, their potential was practically exploited only in non-medical fields of use, although many aerogel materials, either organic, inorganic or hybrid, were proven biocompatible. Some aerogel compositions have been patented at the verge of the millennium, but the clinical use of aerogels remains very limited. This review intends to shed some more light in regard to their potential in biomedical applications as can be deduced from the more recent progressive research of their capabilities in regard to different compositions. The review covers many recent studies, but includes older research that significantly affected the development of aerogel-based materials over the years, as well. After a short introduction, covering the common aerogel properties and their possible classification options, the review is structured based on their different possible biomedical applications. Finally, it focuses on the potential of aerogels in regenerative medicine.Graphical Abstract

Functional wound dressing materials with highly tunable drug release properties

Wound dressings, capable of local controlled delivery of non-steroid anti-inflammatory pain-killing drugs (NSAIDs) to the wound bed, offer great potential to accelerate wound healing, hence increase the quality of patient life. With local NSAID delivery, unwanted side effects encountered in their systemic delivery, are drastically diminished. In this study, four functional fibrous wound dressing materials, namely viscose, alginate, sodium carboxymethyl cellulose (Na-CMC) and polyethylene terephthalate (PET) loaded with a NSAID, diclofenac sodium (DCF) are prepared, and their suitability to tune the release rate of DCF is evaluated. Through careful examination of material–drug combinations, in terms of their physicochemical properties (air permeability, wettability and water retention) and structural/morphological properties (infrared spectroscopy, wide angle X-ray scattering and scanning electron microscopy), possible wound care applications are proposed. In vitro release studies using an automated Franz diffusion cell system, combined with UV-Vis absorption spectroscopy for drug release profile determination, are performed as the final pre-formulation test. Results showed significant differences in the release profiles between different material–drug combinations, making the examined materials highly applicable for several wound care applications. The present study presents a novel cost effective approach for preparation of drug loaded wound dressing materials without a sacrifice in patient safety. Additionally, novel methods and material–drug combinations are introduced, paving the way for possible future wound treatment options.

A review of herbal medicines in wound healing

Herbs have been integral to both traditional and non‐traditional forms of medicine dating back at least 5000 years. The enduring popularity of herbal medicines may be explained by the perception that herbs cause minimal unwanted side effects. More recently, scientists increasingly rely on modern scientific methods and evidence‐based medicine to prove efficacy of herbal medicines and focus on better understanding of mechanisms of their action. However, information concerning quantitative human health benefits of herbal medicines is still rare or dispersed, limiting their proper valuation. Preparations from traditional medicinal plants are often used for wound healing purposes covering a broad area of different skin‐related diseases. Herbal medicines in wound management involve disinfection, debridement, and provision of a suitable environment for aiding the natural course of healing. Here we report on 22 plants used as wound healing agents in traditional medicine around the world. The aim of this review is therefore to review herbal medicines, which pose great potential for effective treatment of minor wounds.

An attempt to use atomic force microscopy for determination of bond type in lithium battery electrodes

Lithium batteries use binders (mostly polymeric) to achieve appropriate mechanical strength of electrodes. The nature of binding between the polymers and the active component, however, is hardly known. In this paper we attempt to establish this nature by using atomic force microscopy (AFM) measurements. In our model study, the interaction between silicon and carboxymethyl cellulose (CMC)—an anode system of considerable practical interest—is studied. We show that, contrary to occasional expectations in the battery community, the use of AFM in such complex systems cannot give direct information about the magnitude of forces between polymer molecules and substrate. Nevertheless, one can use an indirect approach whereby one can tell whether in the particular case strong (e.g. covalent) or weaker (e.g. adsorption) interactions prevail.

Polyester type polyHIPE scaffolds with an interconnected porous structure for cartilage regeneration

Development of artificial materials for the facilitation of cartilage regeneration remains an important challenge in orthopedic practice. Our study investigates the potential for neocartilage formation within a synthetic polyester scaffold based on the polymerization of high internal phase emulsions. The fabrication of polyHIPE polymer (PHP) was specifically tailored to produce a highly porous (85%) structure with the primary pore size in the range of 50–170 μm for cartilage tissue engineering. The resulting PHP scaffold was proven biocompatible with human articular chondrocytes and viable cells were observed within the materials as evaluated using the Live/Dead assay and histological analysis. Chondrocytes with round nuclei were organized into multicellular layers on the PHP surface and were observed to grow approximately 300 μm into the scaffold interior. The accumulation of collagen type 2 was detected using immunohistochemistry and chondrogenic specific genes were expressed with favorable collagen type 2 to 1 ratio. In addition, PHP samples are biodegradable and their baseline mechanical properties are similar to those of native cartilage, which enhance chondrocyte cell growth and proliferation.

Gold nanoparticles in the engineering of antibacterial and anticoagulant surfaces.

Simultaneous antibacterial and anticoagulant surfaces have been prepared by immobilization of engineered gold nanoparticles onto different kinds of surfaces. The gold nanoparticle core is surrounded by a hemocompatible, anticoagulant polysaccharide, 6-O chitosan sulfate, which serves as reduction and stabilizing agent for the generation of gold nanoparticles in a microwave mediated reaction. The particle suspension shows anticoagulant activity, which is investigated by aPTT and PT testing on citrated blood samples of three patients suffering from congenital or acquired bleeding disorders. The amount of nanoparticles deposited on the surfaces is quantified by a quartz crystal microbalance with dissipation unit. All gold containing surfaces exhibit excellent antimicrobial properties against the chosen model organism, Escherichia coli MG 1655 [R1-16]. Moreover, blood plasma coagulation times of the surfaces are increased after deposition of the engineered nanoparticles as demonstrated by QCM-D.

Guest-host van der Waals interactions decisively affect the molecular transport in mesoporous media.

We present clear evidence that the global (macroscopic) transport from/to mesoporous materials is significantly affected by the interactions between the mesoporous host and the guest molecules. The problem is considered in a most general way so the solutions apply for a variety of cases such as the release of a guest from porous matrices, catalysis occurring in porous materials or processes taking place in separation techniques. The concept is proved on the experimentally determined release profiles of a model drug (indomethacin) from accurately designed SBA-15 and MCM-41 mesoporous silicates. In order to allow for a full quantitative analysis, a very high frequency of sampling was carried out at short release times. The agreement between the experimentally determined and the theoretically predicted curves is excellent not only in shape but also in all major trends. In the broadest sense, one might say that the host–guest interactions change the effective cross-section of pores through which the transport of guest occurs. In addition, the interactions lower the efficiency of utilization of the guest. In drug release this is observed as a decrease of released matter at long times, in catalysis this would correspond to a decrease of global turnover efficiency etc. However, it is not only the final outcome that is affected but also the transport pattern (e.g. the shape of release curves) during a wide range of timescales. Our finding might have a profound influence on the design of various devices based on meso- or macroporous materials.

Novel chitosan/diclofenac coatings on medical grade stainless steel for hip replacement applications

Corrosion resistance, biocompatibility, improved osteointegration, as well the prevention of inflammation and pain are the most desired characteristics of hip replacement implants. In this study we introduce a novel multi-layered coating on AISI 316LVM stainless steel that shows promise with regard to all mentioned characteristics. The coating is prepared from alternating layers of the biocompatible polysaccharide chitosan and the non-steroid anti-inflammatory drug (NSAID), diclofenac. Electrochemical methods were employed to characterize the corrosion behavior of coated and uncoated samples in physiological solution. It is shown that these coatings improve corrosion resistance. It was also found that these coatings release the incorporated drug in controlled, multi-mechanism manner. Adding additional layers on top of the as-prepared samples, has potential for further tailoring of the release profile and increasing the drug dose. Biocompatibility was proven on human-derived osteoblasts in several experiments. Only viable cells were found on the sample surface after incubation of the samples with the same cell line. This novel coating could prove important for prolongation of the application potential of steel-based hip replacements, which are these days often replaced by more expensive ceramic or other metal alloys.