Julijana Kristl

University of Ljubljana · Faculty of pharmacy - Nanotechnology group

Conventional treatments for chronic wounds are often ineffective, thus new therapeutic approaches are needed, such as the delivery of immunomodulatory drugs that can reduce inflammation, restore immune cell function, and facilitate tissue regeneration. A potential drug for such an approach is simvastatin, which has major drawbacks including poor so...

Biofilm-associated diseases such as periodontitis are widespread and challenging to treat which calls for new strategies for their effective management. Probiotics represent a promising approach for targeted treatment of dysbiosis in biofilm and modulation of host immune response. In this interdisciplinary study, nanofibers with two autochthonous B...

The lack of appropriate delivery systems hinders the use of probiotics in the treatment of vaginal infections. Therefore, the development of a new delivery system for the local administration of vaginal probiotics is necessary. In this study, we selected three vaginal lactobacilli, i.e., Lactobacillus crispatus, Lactobacillus gasseri, and Lactobaci...

Keeping up with cutting edge research in the field of drug delivery, the overall goal of this study was to develop innovative electrospun nanofibers loaded with ionic liquids (ILs) as active pharmaceutical ingredients (APIs). For the first time, a novel approach was examined by combining biocompatible polymer, poly (ethylene oxide) (PEO), and pharm...

Lactobacilli are a promising natural tool against vaginal dysbiosis and infections. However, new local delivery systems and additional knowledge about their distribution and mechanism of action would contribute to the development of effective medicine. This will be facilitated by the introduction of the techniques for effective, inexpensive, and re...

Oxidative stress is associated with a wide range of diseases characterised by oxidant-mediated disturbances of various signalling pathways and cellular damage. The only effective strategy for the prevention of cellular damage is to limit the production of oxidants and support their efficient removal. The implication of the nuclear factor erythroid...

Although electrostatic modification of bacterial surfaces using polyelectrolytes (PEs) is a convenient and versatile tool for biotechnological processes, the ambiguities in toxicity of PEs between various bacteria and the insufficient understanding of the mechanism of action of cationic PEs and their nano-thick shells formed around the bacteria cre...

The goal of the present work was to determine and characterize the therapeutic feasibility of silk fibroin xerogels as a potential long-acting estradiol delivery system. Fibroin delivery systems were prepared by the addition of ethanol that besides dissolving the drug, served as an accelerator for the gelation of the silk extracted fibroin solution...

The disadvantages of conventional anticancer drugs, such as their low bioavailability, poor targeting efficacy, and serious side effects, have led to the discovery of new therapeutic agents and potential drug delivery systems. In particular, the introduction of nano-sized drug delivery systems (NDDSs) has opened new horizons for effective cancer tr...

Introduction: Periodontitis is a widespread illness that arises due to disrupted interplay between the oral microbiota and the host immune response. In some cases, conventional therapies can provide temporary remission, although this is often followed by disease relapse. Recent studies of periodontitis pathology have promoted the development of new...

Hydrophilic matrix tablets with controlled drug release have been used extensively as one of the most successful oral drug delivery systems for optimizing therapeutic efficacy. In this work, magnetic resonance imaging (MRI) is used to study the influence of various pHs and mechanical stresses caused by medium flow (at rest, 80, or 150 mL/min) on sw...

Previously, we reported on the surfactant cetylpyridinium chloride (CPC) as a crosslinker of alginate for the formation of stable polyelectrolyte–surfactant–complex nanoparticles. Here, we evaluate this system for increased solubility of a poorly soluble drug. The aim was to use CPC for solubilisation of ibuprofen and to use the micellar associates...

Periodontal disease is a widespread chronic condition associated with degradation of periodontal tissues that requires more effective approaches for its treatment. Thus, the aim was to develop a nanodelivery system for local application of antimicrobials, with evaluation in vitro using a newly developed micro flow-through apparatus that simulates l...

Lactic acid bacteria can have beneficial health effects and be used for the treatment of various diseases. However, there remains the challenge of encapsulating probiotics into delivery systems with a high viability and encapsulation efficacy. The electrospinning of bacteria is a novel and little-studied method, and further investigation of its pro...

Alginate is a promising biocompatible and biodegradable polymer for production of nanofibers for drug delivery and tissue engineering. However, alginate is difficult to electrospin due to its polyelectrolyte nature. The aim was to improve the ‘electrospinability’ of alginate with addition of exceptionally high molecular weight poly(ethylene oxide)...

The dynamic properties of water and polymer molecules in xanthan hydrogels at different polymer mass fractions were investigated through the combination of conventional and fast-field cycling NMR relaxation to obtain the information about dynamics in different time scales. The results showed that water dynamics were faster in diluted than in concen...

The interest in probiotics has grown in recent years due to increased awareness of the importance of microbiota for human health. We present the development of monolithic poly(ethylene oxide) and composite poly(ethylene oxide)/lyoprotectant nanofibers loaded with the probiotic Lactobacillus plantarum ATCC 8014. High loading was achieved for L. plan...

Solubility is a physicochemical property highly dependent on the solid-state form of a compound. Thus, alteration of a compound's solid-state form can be undertaken to enhance the solubility of poorly soluble drug compounds. In the Biopharmaceutics Classification System (BCS), drugs are classified based on their aqueous solubility and permeability....

We here aim to provide a detailed protocol to obtain an aged cell culture model, which is conveniently characterised in terms of morphology, metabolism, and key biochemical markers of senescence. Commercial Human Dermal Fibroblasts (HDF) (67-year-old female Asian donor) were cultured over a span of 35 passagesto determine at what passages they expr...

The conventional treatment of periodontal disease does not solve the high incidence of re-colonization of the periodontal pockets by pathogens. Here, we introduce an innovative concept of incorporating autochthonous bacteria as potential probiotics into nanofibers for local treatment. We selected and isolated the strain 25.2.M from the oral microbi...

Oral delivery of protein drugs is greatly limited by low hydrophobicity, an important determinant for intestinal epithelial permeation and bioavailability. Herein, surface properties of recombinant erythropoietin were investigated using the fluorescent dye bis-ANS to monitor relative hydrophobicity for correlation with permeabilities with Caco-2 ce...

Electrospinning enables to design and manufacture novel drug delivery systems capable of advancing the local antibacterial therapy. In this study, two hydrophilic drugs - metronidazole and ciprofloxacin hydrochloride - were loaded both individually and in combination into hydrophobic polycaprolactone (PCL) matrix using electrospinning. We aimed to...

LINK to FULL text (50 days free): https://www.sciencedirect.com/science/article/pii/S0928098718302410 The delivery of probiotics to different sites of action within the human body might help to prevent and treat several diseases. Here, we describe a microcapsule-based system for delivery of probiotic bacteria, as vegetative cells or spores, which...

Here, we combined lipid nanovesicles (ethosomes, liposomes) as the drug carrier systems with two physical methods (electroporation, sonoporation) to enhance transdermal delivery of a hydrophilic model molecule, calcein. First, using different formulations, ethosomes greatly enhanced calcein permeation by passive diffusion compared to liposomes and...

Complexation of linear alginate polyanions with different classes of crosslinkers (divalent cations, polycations, positively charged surfactants) was investigated, to unravel their effects on nanoparticle formation. The goal was to define the crosslinker-to-alginate molar ratios at which nanoparticles are formed, and to reveal the underlying thermo...

Electrospinning was used to produce carvedilol-loaded Soluplus polymer nanofibers using a systematic approach. Miscibility between drug and polymer was determined through calculation of the interaction parameter, χ, and the difference between the total solubility parameters, Δdt. A solubility map for Soluplus was obtained by examining different sol...

The focus was on the development of medicated foam for incorporation of two incompatible active agents for psoriasis treatment; i.e., lipophilic cholecalciferol, and hydrophilic salicylic acid. Emphasis was given to formulation of a propellant-free foam, with sufficient foaming properties, physical and chemical stability, and low irritancy potentia...

Nanofibers combined with an antimicrobial represent a powerful strategy for treatment of various infections. Local infections usually have a low fluid volume available for drug release, whereas pharmacopoeian dissolution tests include a much larger receptor volume. Therefore, the development of novel drug-release methods that more closely resemble...

In this study the development of stable polyelectrolyte-surfactant complex nanoparticles composed of alginate and cetylpyridinium chloride (CPC), with and without ZnCl2, for therapeutic use, is investigated. The mechanism of CPC binding by alginate was analyzed using a cetylpyridinium cation (CP+) selective membrane electrode. The cooperative natur...

Polyelectrolyte complexes are based on ionic interaction between the charged polymer (polyelectrolyte) and the substance with the opposite charge, which can be a polymer, a protein, a surfactant or any other charged substance. Active pharmaceutical ingredients that fall in any of the aforementioned categories, can be incorporated into these complex...

Periodontal disease is a chronic inflammation of periodontal tissues resulting in destruction of the periodontal ligament, root cementum, and alveolar bone, formation of periodontal pockets and teeth loss. In numerous cases, the treatment according to the current guidelines does not lead to the desired outcome, and consequently, new approaches and...

The drug release form polymer matrix tablets is a complex process, greatly influenced by the gel's formation at the tablet surface. Magnetic resonance (MR) is a non-invasive method suitable to determine the gel layer properties by using MR that can provide the information about the gel's properties. MR imaging (MRI) that enables in situ determinati...

Sustained controlled drug release is one of the prominent contributions for more successful treatment outcomes in the case of several diseases. However, the incorporation of hydrophilic drugs into nanofibers, a promising novel delivery system, and achieving a long-term sustained release still pose a challenging task. In this work we demonstrated a...

The formation of a gel coat around xanthan (Xan) tablets, empty or loaded with pentoxifylline (PF), and its release in media differing in pH and ionic strength by NMR, MR imaging and two release methods were studied. The T1 and T2 NMR relaxation times in gels depend predominantly on Xan concentration; the presence of PF has negligible influence on...

Nanofibers represent an attractive novel drug delivery system for prolonged release. However, sustained release of hydrophilic drugs, like ciprofloxacin hydrochloride (CIP), from polymeric nanofibers is not an easy task. The present study investigates the effect of different hydrophobic polymers (PCL and PMMA) alone in monolithic nanofibers, or wit...

Periodontal disease is chronic inflammation of periodontal tissues resulting in formation of periodontal pockets, periodontal attachment loss and progressive destruction of the ligament and alveolar bone. This review gives an update on periodontal disease pathogenesis, which is important for the development of novel methods and delivery systems for...

The number of poorly water-soluble drug candidates is rapidly increasing; this represents a major challenge for the pharmaceutical industry. As a consequence, novel formulation approaches are required. Furthermore, if such a drug candidate is intended for the therapy of a specific group of the population, such as geriatric or pediatric, the formula...

Recently trans-resveratrol (trans-RSV) has received great attention due to its prophylactic and therapeutic properties. Its limited bioavailability provides compelling evidence of the need for more suitable formulations in order to attain better clinical effectiveness. Some physicochemical properties of trans-RSV are still unknown or research findi...

The electrospinning technique for nanofiber production has opened new and interesting opportunities for tissue regeneration and treatment, because they allow biomimetic supports for cell growth to be designed and enable simultaneous delivery of diverse drugs in a controlled manner. In this review the process of electrospinning itself and the parame...

Electrospun polymer nanofibers have opened new opportunities in the rapidly evolving field of tissue engineering, particularly due to their topography and variability of available biomaterials. In order to better understand nanofiber influence on cell growth, the impact of their diameter was systematically examined. In this study homogenous, random...

Thermally induced gelling systems have gained enormous attention over the last decade. They consist of hydrophilic homopolymers or block copolymers in water that present a sol at room temperature and form a gel after administration into the body. This article reviews the main types of thermoresponsive polymers, with special focus on decisive hydrog...

The aim of our work was to produce a modern nanomaterial with incorporated blood-derived growth factors, produced by electrospinning, applicable in treatment of chronic wounds. Platelet-rich plasma was chosen as a natural source of growth factors. Results showed that platelet-rich plasma stimulates keratinocyte and fibroblast cell growth in vitro....

Abstract The idea of creating replacement for damaged or diseased tissue, which will mimic the physiological conditions and simultaneously promote regeneration by patients' own cells, has been a major challenge in the biomedicine for more than a decade. Therefore, nanofibers are a promising solution to address these challenges. These are solid poly...

Electrospinning is an efficient and flexible method for nanofiber production, but it is influenced by many systemic, process, and environmental parameters that govern the electrospun product morphology. This study systematically investigates the influence of relative humidity (RH) on the electrospinning process. The results showed that the morpholo...

This paper especially highlights the finding that the mechanical properties of polymeric nanofibers can be tuned by changing the fiber size as well as the composition. For this purpose, the bending Young's modulus was determined using atomic force microscope by involving single-material (polyvinyl alcohol (PVA), polyethylene oxide (PEO 400K)) and c...

Magnetic resonance imaging was used to study swelling dynamics and hydrogel formation of xanthan tablets with or without Pentoxifylline drug in water and HCl pH 1.2 media at two different ionic strengths. Significant changes were observed only in the erosion front positions leading to different hydrogel thicknesses. The impact of the drug on the hy...

The intracellular fate of nanosized drug delivery systems is still not well understood. Various internalization pathways have been discovered, but knowledge of their intracellular trafficking is still incomplete. The aim of this study was to examine the internalization, pathways, and positioning taken by solid lipid nanoparticles (SLNs) in cells. S...

Superparamagnetic iron oxide nanoparticles (SPIONs) show a great promise for a wide specter of bioapplications, due to their characteristic magnetic properties exhibited only in the presence of magnetic field. Their advantages in the fields of magnetic drug targeting and imaging are well established and their safety is assumed, since iron oxide nan...

Despite a lot of intensive research in the field of polymer nanofibers as wound-healing and tissue-regeneration materials, the behavior of cells in contact with nanofibers in vitro as well as in vivo is still not well understood. However, this knowledge is crucial for the design of nanofibrillar materials that are suitable for biomedical applicatio...

(Full text is available at http://www.manu.edu.mk/prilozi). Modified-release matrix tablets have been extensively used by the pharmaceutical industry as one of the most successful oral drug-delivery systems. The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dis...

The skin is the largest as well as prominent organ of human body, most importantly protecting us from harmful environmental hazards. Cutaneous inflammatory reactions are common adverse effect in humans due to frequent contacts with heterogeneous substances. Irritative contact dermatitis is a term used to describe any inflammatory reaction resulting...

Interfacial rheology: An overview of measuring techniques and its role in dispersions and electrospinning Interfacial rheological properties have yet to be thoroughly explored. Only recently, methods have been introduced that provide sufficient sensitivity to reliably determine viscoelastic interfacial properties. In general, interfacial rheology d...

Nanotechnology has a significant impact on the development of nanomedicines, which represent formulation bionanosystems, targeting drug delivery and tissue engineering including nanoelectronic biosenzors. Preparation, characterization and evaluation need new sophisticated methods, procedures and equipments, different from known before. A brief revi...

In the field of diagnosis and treatment in contemporary medicine, nanoparticles (NPs) are an important novelty. They are drug delivery systems on the nanometer scale, whose uptake mechanisms and routes of internalization differ, depending on their properties. For successful treatment, it is crucially important to understand the interplay between up...

The subject of nanomedicine has seen a surge in research activity over the past decade, with nanofibers being a particularly active field. Nanofibers are solid, dry fibers with nanometer diameters, made of various polymers, whereas electrospinning is a versatile, simple, elegant, reproducible, continuous and scalable technology for their preparatio...

Electrospinning is a unique and versatile technique for the fabrication of nanofibers that mimics the native extracellular matrix for tissue engineering. In this paper, hydroxyethyl cellulose (HEC) has been electrospun. Selected parameters of spinning solutions (viscosity, conductivity and surface tension) and process parameters (applied voltage, n...

To improve visualization of nanoparticles within the cells' compartments, we synthesized a coumarin based fluorescent derivative, tetradecyl diethylamino coumarin amid, 14-DACA. In this compound the coumarin chromophore is linked with a tetradecyl alkyl chain that contributes to lipophilicity and slightly amphiphilic character of this probe. 14-DAC...

The feasibility of incorporating a solid dispersion containing poorly soluble antidiabetic drug glimepiride and poly(ester amide) hyperbranched polymer into a tablet using a direct-compression tabletting technique was investigated. Tablet cores were additionally coated with hydroxypropyl methylcellulose phthalate in order to protect the extremely h...

Over the past few decades, nanoparticle (NP) formulation has been the subject of extensive research. The choice of a suitable NP formulation technique is dependent on the physicochemical properties of the drug, such as solubility and chemical stability. Different NP manufacturing methods enable modification of the physicochemical characteristics su...

Introduction: Magnetic resonance imaging is a powerful, non-invasive technique that can help improve our understanding of the hydrogel layer formed on swellable, polymer-matrix tablets, as well as the layer's properties and its influence on drug release. Areas covered: In this paper, the authors review the NMR and MRI investigations of hydrophil...

Tumor hypoxia is a well known therapeutic problem which contributes to radioresistance and aggressive tumor characteristics. Lack of techniques for repeated measurements of tumor oxygenation (pO2, partial pressure of oxygen) has restricted the optimization of hypoxia modifying methods and their efficacious application with radiotherapy. We have inv...

Systems for storage and distribution of purified water at ambient temperature are highly susceptible to microbial contamination. The water flow, microbial content and chemical quality of the purified water in an industrial water system have been simulated in a biofilm annular reactor (BAR) to study the impact of different hydrodynamic conditions on...

In the present study, chitosan was chosen as an excellent material for tissue scaffold and wound dressing design due to its versatile ability to stimulate the immune system, promote cellular growth, and control bacterial growth. Different mass ratio of blended solutions of 3% (w/w) chitosan in 2% (w/w) acetic acid and 3% (w/w) poly(ethylene oxide)...

The continuous maintaining of acceptable quality of purified water in industrial purified water system that is disinfected by ozone is explained by results of laboratory studies and review of 10 years results of purified water. Laboratory study revealed that biofilm bacteria Stenotrophomonas malthophilia, that constitutes the majority of biofilm in...

Recent advances in nanotechnology applied to proteins are directed towards safer and simpler methods of preparation, using naturally occurring polymers such as alginate, pectin and chitosan. In this study, pectin-chitosan nanoparticles (NPs) were designed by the mild process of polyelectrolyte complexation, which occurs at room temperature without...

Drug delivery into the skin is problematic because, as a natural barrier, it has a very low permeation rate. Several approaches have been made to increase the latter. Current advances in materials science and nanotechnology promise the development of new generations of drug carriers for therapeutic, diagnostic and protective purposes. We have revie...

Sunscreens containing ZnO and TiO(2) nanoparticles (NPs) are increasingly applied to skin over long time periods to reduce the risk of skin cancer. However, long-term toxicological studies of NPs are very sparse. The in vitro toxicity of ZnO and TiO(2) NPs on keratinocytes over short- and long-term applications is reported. The effects studied are...

Modern approach in the wound healing is based on maintenance of moist environment on the wound and as modern dressings hydrogels have been offered. Based on diffrent researches the healing of the wound can be improved by application of growth factors or protease's inhibitors. In the article the development of hydrogels from hydroxyethylcellulose or...

Orlistat is locally acting inhibitor of gastrointestinal lipases which has been developed for the treatment of obesity. The present study was designed with the intent to formulate orlistat in a different way compared to the current practice and investigate its inhibition of gastrointestinal lipases. Orlistat is considered as a technologically probl...

The aim of this work was to study the feasibility of using hyperbranched polymers with highly branched structure and a large number of functional groups as solubilization enhancers for poorly water-soluble drugs. Antidiabetic drug glimepiride was used as a model drug and commercially available hyperbranched poly(esteramide)s as drug carriers. The r...

The key element in drug release from hydrophilic matrix tablets is the gel layer that regulates the penetration of water and controls drug dissolution and diffusion. We have selected magnetic resonance imaging (MRI) as the method of choice for visualizing the dynamic processes occurring during the swelling of xanthan tablets in a variety of media....

Development and progression of breast cancer can be caused by increased estradiol activity, which stimulates cell proliferation. Inhibitors of type 1 17β-hydroxysteroid dehydrogenase (17β-HSD) enzyme inhibit estradiol biosynthesis and therefore have potential anticancer activity. In this study two new trans-cinnamic acid esters were established as...

To improve visualization of nanoparticles within the cells' compartments, we synthesized a coumarin based fluorescent derivative, tetradecyl diethylamino coumarin amid, 14-DACA. In this compound the coumarin chromophore is linked with a tetradecyl alkyl chain that contributes to lipophilicity and slightly amphiphilic character of this probe. 14-DAC...

Drug delivery research has resulted in the availability of several enabling technologies for formulating poorly water-soluble compounds. In this study the vibrating nozzle device, originally used for encapsulation of drugs, cells and microorganisms, has been used to formulate nanoparticles (NP) with high loading capacity. Celecoxib was incorporated...