Pulmonary Sarcoidosis: Experimental Models and Perspectives of Molecular Diagnostics Using Quantum Dots.

Sarcoidosis is a complex inflammatory multisystem disease of unknown etiology that is characterised by epithelioid cell granulomatous lesions affecting various organs, mainly the lungs. In general, sarcoidosis is asymptomatic, but some cases result in severe complications and organ failure. So far, no accurate and validated modelling for clinical and pathohistological manifestations of sarcoidosis is suggested. Moreover, knowledge about disease-specific diagnostic markers for sarcoidosis is scarce. For instance, pulmonary granulomatosis is associated with the upregulated production of proinflammatory molecules: TNF-α, IL-6, CXCL1, CCL2, CCL18, CD163, serum angiotensin-converting enzyme (sACE), lysozyme, neopterin, and serum amyloid A (SAA). Quantum dots (QDs) are widely applied for molecular diagnostics of various diseases. QDs are semiconductor nanoparticles of a few nanometres in size, made from ZnS, CdS, ZnSe, etc., with unique physical and chemical properties that are useful for the labelling and detection in biological experiments. QDs can conjugate with various antibodies or oligonucleotides, allowing for high-sensitivity detection of various targets in organs and cells. Our review describes existing experimental models for sarcoidosis (in vitro, in vivo, and in silico), their advantages and restrictions, as well as the physical properties of quantum dots and their potential applications in the molecular diagnostics of sarcoidosis. The most promising experimental models include mice with TSC2 deletion and an in silico multiscale computational model of sarcoidosis (SarcoidSim), developed using transcriptomics and flow cytometry of human sarcoid biopsies. Both models are most efficient to test different candidate drugs for sarcoidosis.

The Fabrication of Alginate-Carboxymethyl Cellulose-Based Composites and Drug Release Profiles.

Recently, hydrogels based on natural water-soluble polysaccharides have attracted more and more attention due to their favorable characteristics. The high water-holding capacity, lack of toxicity, and biodegradability of such hydrogels make it possible to develop new materials on their basis for biotechnological, biomedical, pharmacological, and medical purposes. Sodium alginate is a non-toxic natural polysaccharide found in marine algae. It is capable of forming solid gels under the action of polyvalent cations that cross-link polysaccharide chains. Alginate-based products are popular in many industries, including food processing, pharmaceutical, and biomedical applications. Cellulose is the most abundant, renewable, and natural polymer on Earth, and it is used for various industrial and biomedical applications. Carboxymethyl cellulose (CMC) is useful in pharmaceutical, food, and non-food industries such as tablets, ice cream, drinks, toothpaste, and detergents. In this review, various methods for the preparation of the compositions based on sodium alginate and CMC using different crosslinking agents have been collected for the first time. Additionally, the drug release profile from such polymer matrixes was analyzed.

In-Vitro Antibacterial Activity of Curcumin-Loaded Nanofibers Based on Hyaluronic Acid against Multidrug-Resistant ESKAPE Pathogens.

Bacterial infections have accompanied humanity throughout its history and became vitally important in the pandemic area. The most pathogenic bacteria are multidrug-resistant strains, which have become widespread due to their natural biological response to the use of antibiotics, including uncontrolled use. The current challenge is finding highly effective antibacterial agents of natural origin, which, however, have low solubility and consequently poor bioavailability. Curcumin, derived from Curcuma longa, is an example of a natural biologically active agent with a wide spectrum of biological effects, particularly against Gram-positive bacteria. However, curcumin exhibits extremely low antibacterial activity against Gram-negative bacteria. Curcumin's hydrophobicity limits its use in medicine. As such, various polymeric systems have been used, especially biopolymer-based electrospun nanofibers. In the present study, the technological features of the fabrication of curcumin-loaded hyaluronic acid-based nanofibers are discussed in detail, their morphological characteristics, wettability, physico-chemical properties, and curcumin release profiles are demonstrated, and their antibacterial activity against multi-drug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are evaluated. It is noteworthy that the fibers containing a stable HA-curcumin complex showed high antibacterial activity against both Gram-positive and Gram-negative bacteria, which is an undeniable advantage. It is expected that the results of this work will contribute to the development of antibacterial drugs for topical and internal use with high efficacy and considerably lower side effects.

Diflunisal Targeted Delivery Systems: A Review.

Diflunisal is a well-known drug for the treatment of rheumatoid arthritis, osteoarthritis, primary dysmenorrhea, and colon cancer. This molecule belongs to the group of nonsteroidal anti-inflammatory drugs (NSAID) and thus possesses serious side effects such as cardiovascular diseases risk development, renal injury, and hepatic reactions. The last clinical data demonstrated that diflunisal is one of the recognized drugs for the treatment of cardiac amyloidosis and possesses a survival benefit similar to that of clinically approved tafamidis. Diflunisal stabilizes the transthyretin (TTR) tetramer and prevents the misfolding of monomers and dimers from forming amyloid deposits in the heart. To avoid serious side effects of diflunisal, the various delivery systems have been developed. In the present review, attention is given to the recent development of diflunisal-loaded delivery systems, its technology, release profiles, and effectiveness.

Mangiferin as New Potential Anti-Cancer Agent and Mangiferin-Integrated Polymer Systems-A Novel Research Direction.

For a long time, the pharmaceutical industry focused on natural biologically active molecules due to their unique properties, availability and significantly less side-effects. Mangiferin is a naturally occurring C-glucosylxantone that has substantial potential for the treatment of various diseases thanks to its numerous biological activities. Many research studies have proven that mangiferin possesses antioxidant, anti-infection, anti-cancer, anti-diabetic, cardiovascular, neuroprotective properties and it also increases immunity. It is especially important that it has no toxicity. However, mangiferin is not being currently applied to clinical use because its oral bioavailability as well as its absorption in the body are too low. To improve the solubility, enhance the biological action and bioavailability, mangiferin integrated polymer systems have been developed. In this paper, we review molecular mechanisms of anti-cancer action as well as a number of designed polymer-mangiferin systems. Taking together, mangiferin is a very promising anti-cancer molecule with excellent properties and the absence of toxicity.

Hyaluronic Acid: The Influence of Molecular Weight on Structural, Physical, Physico-Chemical, and Degradable Properties of Biopolymer.

Hyaluronic acid, as a natural linear polysaccharide, has attracted researchers' attention from its initial detection and isolation from tissues in 1934 until the present day. Due to biocompatibility and a high biodegradation of hyaluronic acid, it finds wide application in bioengineering and biomedicine: from biorevitalizing skin cosmetics and endoprostheses of joint fluid to polymeric scaffolds and wound dressings. However, the main properties of aqueous polysaccharide solutions with different molecular weights are different. Moreover, the therapeutic effect of hyaluronic acid-based preparations directly depends on the molecular weight of the biopolymer. The present review collects the information about relations between the molecular weight of hyaluronic acid and its original properties. Particular emphasis is placed on the structural, physical and physico-chemical properties of hyaluronic acid in water solutions, as well as their degradability.

Curcumin/Usnic Acid-Loaded Electrospun Nanofibers Based on Hyaluronic Acid.

Hyaluronic acid, curcumin, and usnic acid are separately utilized as effective biological agents in medicine, and materials based on its blend are considered to have wider therapeutic effects than individual ones. In this study, for the first time, native hyaluronic acid-based fibers containing curcumin and usnic acid with an average diameter of 298 nm were successfully prepared by the electrospinning technique and characterized. Additionally, unstable and hydrophobic curcumin and usnic acid were loaded into the hydrophilic hyaluronic acid matrix without utilizing the activating (catalyzing) agents, resulting in the formation of an electrospinnable solution. Only the binary mixture deionized water-dimethyl sulfoxide (50:50)-was used as solvent. The presence of small amounts of dimethyl sulfoxide in the fibrous materials was expected to provide the materials with local anesthetic and antiseptic activity. The effect of electric voltage on the electrospinning process, diameter, and morphology of hyaluronic acid/curcumin/usnic acid fibers was investigated in detail. The impact of curcumin and usnic acid on the stability of fiber formation was observed. The investigation of fibers based on pure hyaluronic acid without additional polymers and with active pharmaceutical ingredients will lay the groundwork for the development of highly effective wound dressings and new drug delivery scaffolds.

Hyaluronan-Based Nanofibers: Fabrication, Characterization and Application.

Nano- and microfibers based on biopolymers are some of the most attractive issues of biotechnology due to their unique properties and effectiveness. Hyaluronan is well-known as a biodegradable, naturally-occurring polymer, which has great potential for being utilized in a fibrous form. The obtaining of fibers from hyaluronan presents a major challenge because of the hydrophilic character of the polymer and the high viscosity level of its solutions. Electrospinning, as the advanced and effective method of the fiber generation, is difficult. The nano- and microfibers from hyaluronan may be obtained by utilizing special techniques, including binary/ternary solvent systems and several polymers described as modifying (or carrying), such as polyethylene oxide (PEO) and polyvinyl alcohol (PVA). This paper reviews various methods for the synthesis of hyaluronan-based fibers, and also collects brief information on the properties and biological activity of hyaluronan and fibrous materials based on it.