Gene Therapy in the Light of Lifestyle Diseases: Budesonide, Acetaminophen and Simvastatin Modulates rAAV Transduction Efficiency.

Recombinant AAV (rAAV) vectors are increasingly favored for gene therapy due to their useful features of vectorology, such as transfection of dividing and nondividing cells, the presence of tissue-specific serotypes, and biosafety considerations. This study investigates the impact of commonly used therapeutic drugs-acetaminophen, budesonide, and simvastatin-on rAAV transduction efficiency in HEK-293 cells. Cells were transduced with an AAV mosaic vector under the control of a cytomegalovirus (CMV) promoter encoding green fluorescent protein (GFP). Transduction efficiency was assessed by qPCR and fluorescent microscopy. Analysis of functional interactions between genes potentially involved in rAAV transduction in drug-exposed cells was also performed. This study showed a clear effect of drugs on rAAV transmission. Notably, acetaminophen enhanced transduction efficiency by 9-fold, while budesonide and simvastatin showed 2-fold and 3-fold increases, respectively. The gene analysis illustrates the possible involvement of genes related to cell membranes in the potentiation of rAAV transduction induced by the drugs under investigation. Attention should be paid to S100A8, which is a common drug-modified gene for drugs showing anti-inflammatory effects (budesonide and simvastatin), demonstrating an interaction with the gene encoding the receptor for AAV (HGFR). This study underscores the significance of assessing rAAV pharmacokinetics/pharmacodynamics (PKs/PDs) and drug-gene therapy interactions in optimizing gene therapy protocols.

Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.

The Central Nervous System (CNS) is vulnerable to a range of diseases, including neurodegenerative and oncological conditions, which present significant treatment challenges. The blood-brain barrier (BBB) restricts molecule penetration, complicating the achievement of therapeutic concentrations in the CNS following systemic administration. Gene therapy using recombinant adeno-associated virus (rAAV) vectors emerges as a promising strategy for treating CNS diseases, demonstrated by the registration of six gene therapy products in the past six years and 87 ongoing clinical trials. This review explores the implementation of rAAV vectors in CNS disease treatment, emphasizing AAV biology and vector engineering. Various administration methods-such as intravenous, intrathecal, and intraparenchymal routes-and experimental approaches like intranasal and intramuscular administration are evaluated, discussing their advantages and limitations in different CNS contexts. Additionally, the review underscores the importance of optimizing therapeutic efficacy through the pharmacokinetics (PK) and pharmacodynamics (PD) of rAAV vectors. A comprehensive analysis of clinical trials reveals successes and challenges, including barriers to commercialization. This review provides insights into therapeutic strategies using rAAV vectors in neurological diseases and identifies areas requiring further research, particularly in optimizing rAAV PK/PD.

Stability Studies, Biodegradation Tests, and Mechanical Properties of Sodium Alginate and Gellan Gum Beads Containing Surfactant.

The excessive presence of single-use plastics is rapidly degrading our natural environment on a global scale due to their inherent resistance to decomposition. Wet wipes used for personal or household purposes contribute significantly to the accumulation of plastic waste. One potential solution to address this problem involves developing eco-friendly materials that possess the ability to degrade naturally while retaining their washing capabilities. For this purpose, the beads from sodium alginate, gellan gum, and a mixture of these natural polymers containing surfactant were produced using the ionotropic gelation method. Stability studies of the beads by observing their appearance and diameter were performed after incubation in solutions of different pH values. The images showed that macroparticles were reduced in size in an acidic medium and swelled in solution of pH-neutral phosphate-buffered saline. Moreover, all the beads first swelled and then degraded in alkaline conditions. The beads based on gellan gum and combining both polymers were the least sensitive to pH changes. The compression tests revealed that the stiffness of all macroparticles decreased with the increasing pH of the solutions in which they were immersed. The studied beads were more rigid in an acidic solution than in alkaline conditions. The biodegradation of macroparticles was assessed using a respirometric method in soil and seawater. It is important to note that the macroparticles degraded more rapidly in soil than in seawater.

Physicochemical and Antibacterial Properties of Alginate Films Containing Tansy (Tanacetum vulgare L.) Essential Oil.

Tansy (Tanacetum vulgare) is a common plant used in folk medicine for digestive problems, fevers, and migraines; against parasites; and as an insect repellent. The active substances in essential oil are responsible for its antimicrobial and antioxidant activity. Thus, tansy essential oil (TO) was added to alginate films to fabricate materials with antioxidant and antibacterial properties for food packaging. Sodium alginate films with glycerol and TO were tested in terms of structure, mechanical, thermal, antioxidant, and antibacterial properties. The structure of the films was examined using SEM and an ATR-FTIR spectrophotometer. The addition of TO to the alginate film significantly changed the films' microstructure, making them rougher and porous. A low-intensity band at 1739 cm-1, indicative of the presence of TO, appeared in all spectra of alginate films with TO. Moreover, the studies revealed that essential oil acted as a plasticizer, slightly reducing tensile strength from about 7 MPa to 5 MPa and increasing elongation at break from 52% to 56% for the sample with 2% TO. The alginate films enriched in TO exhibited antioxidant properties (280 µmol Trolox/100 g of the sample with 2% TO) and antibacterial activity against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.

Freeze-Dried Matrices Composed of Degradable Polymers with Surfactant-Loaded Microparticles Based on Pectin and Sodium Alginate.

Gelatin/polyvinylpyrrolidone/hydroxyethyl cellulose/glycerol porous matrices with microspheres made of sodium alginate or pectin and sodium alginate were produced. A surfactant was loaded into these microparticles. The microspheres were characterized using optical microscopy, scanning electron microscopy SEM, and laser diffraction particle size analyzer. For the matrices, the density, porosity, swelling capacity, dissolution in phosphate saline buffer were determined and SEM, mechanical, and thermogravimetric studies were applied. The results showed that the size of the two-component microspheres was slightly larger than that of single-ingredient microparticles. The images confirmed the spherical shape of the microparticles. The prepared matrices had high water uptake ability and porosity due to the presence of hydrophilic polymers. The presence of microparticles in the matrices caused a decrease in these parameters. Degradation of the composites with the microspheres was significantly faster than the matrix without them. The addition of microparticles increased the stiffness and toughness of the prepared materials. The efficiency of the thermal decomposition main stage was reduced in the samples with microspheres, whereas a char residue increased in these composites.

Modification of Collagen/Gelatin/Hydroxyethyl Cellulose-Based Materials by Addition of Herbal Extract-Loaded Microspheres Made from Gellan Gum and Xanthan Gum.

Because consumers are nowadays focused on their health and appearance, natural ingredients and their novel delivery systems are one of the most developing fields of pharmacy, medicine, and cosmetics. The main goal of this study was to design, prepare, and characterize composite materials obtained by incorporation of microspheres into the porous polymer materials consisting of collagen, gelatin, and hydroxyethyl cellulose. Microspheres, based on gellan gum and xanthan gum with encapsulated Calendula officinalis flower extract, were produced by two methods: extrusion and emulsification. The release profile of the extract from both types of microspheres was compared. Then, obtained microparticles were incorporated into polymeric materials with a porous structure. This modification had an influence on porosity, density, swelling properties, mechanical properties, and stability of materials. Besides, in vitro tests were performed using mouse fibroblasts. Cell viability was assessed with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The obtained materials, especially with microspheres prepared by emulsion method, can be potentially helpful when designing cosmetic forms because they were made from safely for skin ingredients used in this industry and the herbal extract was successfully encapsulated into microparticles.

Effect of plasticizer and surfactant on the properties of poly(vinyl alcohol)/chitosan films.

The objective of this study was to develop eco-friendly films based on poly(vinyl alcohol) (PVA) and chitosan (CTS) with the addition of plasticizer (glycerol or sorbitol) and surfactant (cocamidopropyl betaine). The properties of the obtained polymeric films were determined by contact angle measurements, attenuated total reflection infrared spectroscopy (ATR-FTIR), atomic force microscopy (AFM), mechanical tests, and moisture content analysis. The results indicated that four-component blends had high surface hydrophilicity and surface roughness due to the presence of the surfactant. Glycerol incorporation into PVA/CTS blends resulted in higher flexibility and greater water absorption capacity of the three- and four-component polymeric blends compared with these blends with sorbitol. By contrast, the addition of the surfactant to the materials is essential for their application in personal hygiene products as disposable wipes.

Microparticles based on natural and synthetic polymers for cosmetic applications.

Most peeling products (exfoliators) available on the market, used in cosmetic and aesthetic dermatology applications, contain synthetic microbeads as abrasive agents. After being released into the natural environment, these non-biodegradable microparticles have an adverse impact on it, especially on aquatic ecosystems. Cosmetics consisting of solid plastic particles will be prohibited in the European Union from 2020. Therefore, there is a great need to develop effective abrasive substances for cosmetic industry. An alternative to synthetic beads may be beads based on biopolymers. Spherical microparticles of sodium alginate and mixture of sodium alginate and starch were obtained using encapsulator BÜCHI B-395 Pro. The obtained microparticles were added to the developed peeling formulation. Subsequently, the evaluation of skin condition after application of peelings with alginate, alginate-starch and synthetic microparticles was made, including topography, skin's barrier quality, hydration, colour, and the level of sebum. The peeling containing sodium alginate and sodium alginate with starch beads does not irritate the skin - redness of skin, itching and dryness did not appear. Microparticles of sodium alginate and sodium alginate with starch act on the skin as effectively as commercial synthetic particles, therefore they may be successfully used as abrasive ingredients in the developed recipe.

Collagen/Gelatin/Hydroxyethyl Cellulose Composites Containing Microspheres Based on Collagen and Gelatin: Design and Evaluation.

The objective of this study was to develop three-dimensional collagen/gelatin/hydroxyethyl cellulose composites in combination with gelatin or collagen-gelatin loaded microspheres. Microspheres were prepared by an emulsification/crosslinking method. A 1-Ethyl-3-(3-dimethyl-aminopropyl)-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) mixture were used as a crosslinking agent for the obtained materials. The structure of the materials was studied using scanning electron microscopy (SEM) and infrared spectroscopy. Moreover, a Calendula officinalis (pot marigold) flower extract release profile of the microsphere-loaded matrices was assessed in vitro. Additionally, porosity, density, stability, swelling and mechanical properties were tested. On the basis of SEM images, the microspheres exhibited a spherical shape and were irregularly dispersed in the polymer matrix. However, it was found that the addition of microparticles to obtained materials did not significantly change their microstructure. We observed a slight decrease in the swelling properties of matrices and an increase in values of Young's modulus. Significantly, the addition of microspheres to the polymer matrices led to improved loading capacity of materials and release performance of Calendula officinalis flower extract. This makes the collagen/gelatin/hydroxyethyl cellulose composites containing microspheres a promising and suitable vehicle for biomedical, dermatological, or cosmetic applications.