Dimitris G Fatouros

Aristotle University of Thessaloniki | AUTH · School of Pharmacy

Gastroretentive drug delivery systems can improve adherence in patients with chronic diseases (CDs), but current options lack dose flexibility and involve complex fabrication methods. Inspired by the hygroscopic deformation observed in multilayered pine cone scales, wherein hydration of the outer active layer induces cone closure, a one‐step fabric...

Background/Objectives: Exosomes, nano-sized extracellular vesicles released by all cells, play a key role in intercellular communication and carry tumorigenic properties that impact surrounding or distant cells. The complexity of the exosomal molecular interactome and its effects on recipient cells still remain unclear. This study aims to decipher...

Citation: Machla, F.; Bekiari, C.; Monou, P.K.; Kofidou, E.; Theodosaki, A.M.; Katsamenis, O.L.; Zisis, V.; Kokoti, M.; Bakopoulou, A.; Fatouros, D.; et al. Development of an Oral Epithelial Ex Vivo Organ Culture Model for Biocompatibility and Permeability Assessment of Biomaterials. Abstract: In the present study, a customized device (Epi-ExPer) w...

Cannabis seed oil oleogel structured with Glycerol Monostearate (20% w/w) was mixed with xanthan gum hydrogel (2% w/w) at different ratios ranging from 0% w/w hydrogel to 75% w/w hydrogel, using a syringe-to-syringe apparatus, for the preparation of 3D-printable food inks. This process enabled the simultaneous blend of oleogel and hydrogel phases a...

Microneedle (MN) patches are gaining increasing attention as a cost-effective technology for delivering drugs directly into the skin. In the present study, two different 3D printing processes were utilized to produce coated MNs, namely, digital light processing (DLP) and semisolid extrusion (SSE). Donepezil (DN), a cholinesterase inhibitor administ...

In this research, 3D-printed antifungal buccal films (BFs) were manufactured as a potential alternative to commercially available antifungal oral gels addressing key considerations such as ease of manufacturing, convenience of administration, enhanced drug efficacy and suitability of paediatric patients. The fabrication process involved the use of...

The theoretical interpretation of the vaginal permeability phenomenon, the evaluation of the suitability of five artificial membranes, and the prediction of the behaviors of vaginal drugs were the main objectives of this study. Franz vertical diffusion cells and different validated HPLC methods were used to measure the permeability of six vaginally...

Rheological analysis of citrus pectin at pH 3 and 7 elucidates its structural dynamics, revealing distinct behaviors influenced by pH. At pH 3, pectin exhibits shear‐thinning, with solvent‐independent unified rheological profiles identifying three concentration regimes: 0.5%–1.5%, 2%–3%, and 3.5%–4%. These regimes, alongside Cox–Merz superpositions...

Introduction: Medication errors during drug manipulations in pediatric care pose significant challenges to patient safety and optimal medication management. Epidemiological studies have revealed a high prevalenceof medication errors throughout the medication process. Due to the lack of age-appropriate dosage forms, medication manipulation is commo...

Homotaurine (HOM) is considered a promising drug for the treatment of Alzheimer’s and other neurodegenerative diseases. In the present work, a new high-performance liquid chromatography with fluorescence detection (HPLC–FLD) (λex. = 340 nm and λem. = 455 nm) method was developed and validated for the study of substance permeability in the central n...

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a...

Buccal foams containing omeprazole (OME) have been developed as potential drug delivery systems for individuals encountering swallowing difficulties, particularly pediatric and geriatric patients. The buccal foams were formulated from lyophilized aqueous gels of maltodextrin, used as a sweetener, combined with various polymers (alginate, chitosan,...

Purpose: The aim of this study was to evaluate the polymerization efficiency of a preheated resin composite used as a luting agent for indirect restorations light-cured by a blue diode laser (445 nm). Methods: Bronze molds were used to prepare cylindrical specimens of a laboratory composite (Ceramage) with dimensions 2, 3, and 4 mm in height and...

The role of mesenchymal-to-endothelial transition in the angiogenic response is controversial. Toward this, the present study aimed to determine if fibroblasts contribute to angiogenesis. Endothelial differentiation of fibroblasts was induced by culturing MRC-5 cells (human fetal lung fibroblast cells) on top of Matrigel hydrogel or embedded inside...

Continuing what previous studies had also intended, the present study aims to shed light on some unanswered questions concerning a recently introduced class of high drug loading (HD) amorphous solid dispersions (ASDs), based on the in-situ thermal crosslinking of poly (acrylic acid) (PAA) and poly (vinyl alcohols) (PVA). Initially, the effect of su...

The current availability of dosage forms for patients with special requirements, such as pediatrics, is low while often leading to poor acceptability and inadequate treatment adherence. As a result, unlicensed and off-labeled preparations are common, exposing patients to unpredictable risks. During the last years, there is an obvious momentum for d...

Objective: Vaginal administration is an important alternative to the oral route for both topical and systemic use. Therefore, the development of reliable in silico methods for the study of drugs permeability is becoming popular in order to avoid time-consuming and costly experiments. Methods: In the current study, Franz cells and appropriate HPL...

Objectives In the present study, a microneedle device (Dermaroller ®) with different needle lengths (1 and 1.5 mm) were used to enhance the transport of a model macromolecular compound (FITC-Dextran 4.4 kDa) across the skin tissue. Methods Transport studies were followed by tape stripping method, to monitor the drug distribution in the stratum cor...

There is a great interest nowadays, in the research for wound dressings that promote the healing process of skin injuries. These dressings protect the wounds from infections while speeding up the healing of the injured area. In present study, wound healing films were fabricated using electrospinning. Electrospinning is a one-step process and it is...

In the original publication [...]

Semi-solid extrusion (SSE) 3D printing technology was utilized for the encapsulation of octreotide acetate (OCT) into 3D-printed oral dosage forms in ambient conditions. The inks and the OCT-loaded 3D-printed oral dosage forms were characterized by means of rheology, Fourier-transform infrared (FTIR) spectroscopy and Nuclear Magnetic Resonance (NMR...

Novel high drug loading amorphous solid dispersions (HDASDs) based on the in situ thermal crosslinked polymeric carriers/matrices have been recently introduced as an upcoming class of drug delivery systems. In this set framework, the present article extends the work of previously published studies by scrutinizing the processes and mechanisms involv...

Medium Chain Triglyceride (MCT) oil was successfully combined with Glyceryl Monostearate (GMS) and Glyceryl Monoolein (GMO) to form oleogels that were subsequently whipped to form stable oleofoams. The co-crystallization of GMS and GMO at a ratio of 20:1, 20:2.5, and 20:5 within MCT oil was studied through Differential Scanning Calorimetry (DSC), X...

Teat sealants are used to prevent intramammary infections. Existing products must be discarded at the onset of lactation to avoid consumption by newborns. The objective was to evaluate the efficacy of an edible, olive oil-based teat sealant namely “MASTIN” against infections of the udder and its’ interaction with teat canal and cistern mucosa, duri...

A new method was developed and validated for the simultaneous determination of nicotine and tobacco-specific nitrosamines (TSNAs) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and N -nitrosonornicotine (NNN) in two different tests matrices: porcine buccal epithelium tissue and phosphate buffered saline (PBS) extracts of smokeless tobacco pro...

A fast and green ultra high‐performance LC method was developed for the determination of ibuprofen in milk‐containing simulated gastrointestinal media to monitor the dissolution of three‐dimensional printed formulations. To remove interfering compounds, protein precipitation using methanol as a precipitation reagent was performed. The separation of...

The current study describes the design of a cost-effective drug delivery apparatus that can be manufactured, assembled, and utilized as easily and quickly as possible, minimizing the time and expense of the supply chain. This apparatus could become a realistic alternative method of providing a vaccine or drug in harsh circumstances, including human...

In this study, drug carrier nanoparticles comprised of Pluronic-F127 and cannabidiol (CBD) or cannabigerol (CBG) were developed, and their wound healing action was studied. They were further incorporated in 3D printed films based on sodium alginate. The prepared films were characterized morphologically and physicochemically and used to evaluate the...

Pharmaceutical compounding is a core activity in the preparation of patient-specific dosage forms. In the current study we aimed to investigate whether 3D printing could be employed for the preparation of pediatric-friendly personalized dosage forms that fulfil the acceptance criteria specified in the pharmacopoeias for conventional dosage forms. W...

Herein, a simple and rapid HPLC method for the determination of paracetamol milk-containing biorelevant media is proposed. The separation of the analyte from the milk-containing biorelevant media was accomplished isocratically using a mobile phase containing 25 mM phosphate buffer (pH = 3.0) and methanol, 80:20, v/v at a flow rate of 1 mL min−1. Fo...

Controlled-release tablets and rectal suppositories of sulfasalazine (SLF) and hydrocortisone 21-acetate (HA) were prepared as recommended dosage forms for the treatment of acute episodes of ulcerative colitis, in patients who do not respond to monotherapy. A High-Performance Liquid Chromatography (HPLC) Diode-array method with a gradient elution m...

The implementation of porous inorganic materials in the delivery of therapeutic molecules facilitates the manipulation over their delivery performance in order to achieve optimal targeted application with the desired pharmacokinetic properties. Mesoporous silica materials are silica matrices containing an extended void network where the drug can be...

In an effort to combine a child-friendly dosage form for medication administration in hospitalized pediatric patients and a user-friendly automated process for its preparation by health-care providers, the current study proposes a method for drug administration with breakfast using semi-solid extrusion 3D printing. Cereal was used as the platform c...

Microneedles (MN) are miniature devices of a maximum length of 1000 μm, capable of perforating painlessly stratum corneum and releasing their active content in the skin layers beneath. The significance of MNs lies on the fact that they have the potential to substitute the fear inducing injections, while avoiding first pass effect or other possibly...

In an effort to combat the effects of endodontic infection, root canal treatment aims to remove endodontic bacteria. Nevertheless, endodontic treatment failure may occur due to microbial persistence and reinfection. Guidelines on dental infection management recommend triple antibiotic paste (TAP), a mixture of ciprofloxacin, metronidazole and minoc...

The technological revolution has physically affected all manufacturing domains, at the gateway of the fourth industrial revolution. Three-dimensional (3D) printing has already shown its potential in this new reality, exhibiting remarkable applications in the production of drug delivery systems. As part of this concept, personalization of the dosage...

In this article, a UHPLC-PDA method has been developed using the quality-by-design (QbD) principles for the determination of the therapeutic peptide – octreotide – in its in vitro released samples. Due to the complexity of the peptide-based hydrogel matrix a reliable separation of the analyte from the matrix has to be performed. Risk assessment and...

Periodontal disease is associated with chronic inflammation and destruction of the soft and hard tissues in the periodontium. Scaffolds that would enable cell attachment and proliferation while at the same time providing a local sustained anti-inflammatory action would be beneficial in restoring or reversing disease progression. In the current stud...

The study aimed to fabricate naproxen sodium loaded in-situ gels of sodium alginate. Different in-situ gel forming solutions of naproxen sodium and sodium alginate were prepared and gel formation was studied in different physiological ions i.e., CaCl2 and Ca-gluconate. The prepared gel formulations were evaluated for different physical attributes s...

Fibrillar structures derived from plant or animal origin have long been a source of inspiration for the design of new biomaterials. The Asn-Gly-Ile-Trp-Tyr-NH2 (NGIWY-amide) pentapeptide, isolated from the sea cucumber Apostichopus japonicus, which spontaneously self-assembles in water to form hydrogel, pertains to this category. In this study, we...

Microneedles (MN) are miniature devices capable of perforating painlessly stratum corneum and delivering active ingredients in the inner epidermal layers. Hollow microneedles (HMNs) are highly detailed objects due to their internal microchannels and thus, their fabrication with Additive Manufacturing (AM) is a challenging task. Vat polymerization t...

In the current study hollow microneedles (HMNs) were fabricated by means of vat polymerization method for the transdermal delivery of insulin. Two geometries of HMNs were designed in a Computer Aided Design (CAD) software namely, curved pyramid and syringe-like and fabricated with Liquid Crystal Display (LCD) method. Dimensions were determined and...

Alginate-based hydrogel inks are commonly used in printing due to their biocompatibility, biodegradation, and cell adhesion. In the present work, 3D printing of hydrogels comprising alginate/methyl cellulose (MC)/trimethyl chitosan (TMC) and silicate glasses was investigated. It was found that TMC increased the stability of the scaffolds after imme...

Objectives The development of age-appropriate dosage forms is essential for effective pharmacotherapy, especially when long-term drug treatment is required, as in the case of latent tuberculosis infection treatment with up to 9 months of daily isoniazid (ISO). Herein, we describe the fabrication of starch-based soft dosage forms of ISO using semi-s...

To cover the unpleasant taste of amoxicillin (250mg), maize starch (baby food) and milk chocolate were co-formulated. The raw materials and the final formulations were characterized by means of Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared (FT-IR) spectroscopy. To evaluate the taste masking t...

The present study examined the microstructure as well as the physicochemical properties of human milk during the second year of lactation in an attempt to explore its applicability for the formulation of food products. It was observed that human milk fat globules (MFG) droplet size increased within 3 days of milk extraction due to coalescence, as e...

In the last decade, additive manufacturing (AM) technologies have revolutionized how healthcare provision is envisioned. The rapid evolution of these technologies has already created a momentum in the effort to address unmet personalized needs in large patient groups, especially those belonging to sensitive subgroup populations (e.g., paediatric, g...

In the present study, a multi-component system comprised of dipalmitylphospatidylcholine (DPPC), Chitosan, Lactose, and L-Leucine was developed for pulmonary delivery. Microparticles were engineered by the spray drying process and the selection of the critical parameters was performed by applying experimental design. The microcarriers with the appr...

Molecular self-assembly has forged a new era in the development of advanced biomaterials for local drug delivery and tissue engineering applications. Given their innate biocompatibility and biodegradability, self-assembling peptides (SAPs) have come in the spotlight of such applications. Short and water-soluble SAP biomaterials associated with enha...

Customization of pharmaceutical products is a central requirement for personalized medicines. However, the existing processing and supply chain solutions do not support such manufacturing-on-demand approaches. In order to solve this challenge, three-dimensional (3D) printing has been applied for customization of not only the dose and release charac...

Introduction: The current availability in dosage forms designed specifically for children is limited, constituting common practice the use of unlicensed or off-labeled medicines and extemporaneous preparations. Swallowing difficulties and taste aversion are the primary reasons for medicine rejection, therefore enhancing palatability and ease of ad...

Two different types of ordered mesoporous nanoparticles, namely MCM-41 and MCM-48, with similar pore sizes but different pore connectivity, were loaded with aprepitant via a passive diffusion method. The percentage of the loaded active agent, along with the encapsulation efficiency, was evaluated using High-performance Liquid Chromatography (HPLC)...

Personalized drug delivery systems are considered an interesting perspective of the 3D printing technology, with the potential to counterbalance the pharmacological and adverse effects of pharmaceutical products. Our study was focused on the utilization of the pressure-assisted microsyringes technology to fabricate patient-tailored lidocaine-loaded...

The present study aimed to fabricate a hollow microneedle device consisting of an array and a reservoir by means of 3D printing technology for transdermal peptide delivery. Hollow microneedles (HMNs) were fabricated using a biocompatible resin material, while PLA filament was used for the reservoirs. The fabricated microdevice was characterized by...

A novel High-Performance Liquid Chromatography-Tandem Mass Spectrometry (HPLC-MS/MS) method was developed for the simultaneous determination of the in vitro skin permeation profile of four UV filters. The sunscreen products contained the following components: octocrylene (OC), ethylhexyl methoxycinnamate (EHMC), diethylamino hydroxybenzoyl hexyl be...

Cannabidiol (CBD) and cannabigerol (CBG) are two active pharmaceutical ingredients, derived from cannabis plant. In the present study, CBD and CBG were formulated with polyvinyl(pyrrolidone) (PVP) and Eudragit L-100, using electrohydrodynamic atomization (electrospinning). The produced fibers were smooth and uniform in shape, with average fiber dia...

The three-dimensional (3D) printing technology has recently emerged in the pharmaceutical field, providing an array of applications for individualized dosing and elaborate formulation designs. However, an alternative asset of the 3D printing technology is the capability to imprint haptic identifiers directly onto the surface of the formulations. Th...

Buccal films containing two vitamins, i.e., thiamine hydrochloride (THCl) and nicotinic acid (NA), were fabricated via two-dimensional (2D) inkjet printing. For the preparation of buccal films, solubility studies and rheological evaluations were conducted in distilled water and propylene-glycol (PG) as main solvent and viscosity/surface tension mod...

Lipid-based drug delivery systems (LbDDS), such as self-nanoemulsifying drug delivery systems (SNEDDS), constitute a prominent formulation approach for enhancing the aqueous solubility and oral bioavailability of poorly water-soluble compounds. Utilization of biorefinery wastes, such as oil from rice bran, may prove advantageous to both improving d...

Exosome selectivity mechanisms underlying exosome–target cell interactions and the specific traits affecting their capability to communicate still remain unclear. Moreover, the capacity of exosomes to efficiently deliver their molecular cargos intracellularly needs precise investigation towards establishing functional exosome‐based delivery platfor...