Unveiling the potential of biomaterials and their synergistic fusion in tissue engineering.

Inspired by nature, tissue engineering aims to employ intricate mechanisms for advanced clinical interventions, unlocking inherent biological potential and propelling medical breakthroughs. Therefore, medical, and pharmaceutical fields are growing interest in tissue and organ replacement, repair, and regeneration by this technology. Three primary mechanisms are currently used in tissue engineering: transplantation of cells (I), injection of growth factors (II) and cellular seeding in scaffolds (III). However, to develop scaffolds presenting highest potential, reinforcement with polymeric materials is growing interest. For instance, natural and synthetic polymers can be used. Regardless, chitosan and keratin are two biopolymers presenting great biocompatibility, biodegradability and non-antigenic properties for tissue engineering purposes offering restoration and revitalization. Therefore, combination of chitosan and keratin has been studied and results exhibit highly porous scaffolds providing optimal environment for tissue cultivation. This review aims to give an historical as well as current overview of tissue engineering, presenting mechanisms used and polymers involved in the field.

Phosphatase-degradable nanoparticles providing sustained drug release.

AIM: The study aimed to develop enzyme-degradable nanoparticles comprising polyphosphates and metal cations providing sustained release of the antibacterial drug ethacridine (ETH). METHODS: Calcium polyphosphate (Ca-PP), zinc polyphosphate (Zn-PP) and iron polyphosphate nanoparticles (Fe-PP NPs) were prepared by co-precipitation of sodium polyphosphate with cations and ETH. Developed nanocarriers were characterized regarding particle size, PDI, zeta potential, encapsulation efficiency and drug loading. Toxicological profile of nanocarriers was assessed via hemolysis assay and cell viability on human blood erythrocytes and HEK-293 cells, respectively. The enzymatic degradation of NPs was evaluated in presence of alkaline phosphatase (ALP) monitoring the release of monophosphate, shift in zeta potential and particle size as well as drug release. The antibacterial efficacy against Escherichia coli was determined via microdilution assay. RESULTS: NPs were obtained in a size range between 300 - 480 nm displaying negative zeta potential values. Encapsulation efficiency was in the range of 83.73 %- 95.99 %. Hemolysis assay underlined sufficient compatibility of NPs with blood cells, whereas drug and NPs showed a concentration dependent effect on HEK-293 cells viability. Ca- and Zn-PP NPs exhibited remarkable changes in zeta potential, particle size, monophosphate and drug release upon incubation with ALP, compared to Fe-PP NPs showing only minor differences. The released ETH from Ca- and Zn-PP nanocarriers retained the antibacterial activity against E. coli, whereas no antibacterial effect was observed with Fe-PP NPs. CONCLUSION: Polyphosphate nanoparticles cross-linked with divalent cations and ETH hold promise for sustained drug delivery triggered by ALP for parental administration.

Inhibition of P-glycoprotein-mediated efflux by thiolated cyclodextrins.

Overcoming P-glycoprotein (P-gp)-mediated efflux poses a significant challenge for the pharmaceutical industry. This study investigates the potential of thiolated ß-cyclodextrins (ß-CD-SHs) as inhibitors of P-gp-mediated efflux in Caco-2 cells. Through a series of transport assays, intracellular accumulation, and efflux of the P-gp substrates Rhodamine 123 (Rh123) and Calcein-AM with and without co-administration of ß-CD-SHs were assessed. The results revealed that the cellular uptake of Rh123 and Calcein-AM were enhanced up to 7- and 3-fold, compared to the control, respectively. In efflux studies an up to 2.5-fold reduction of the Rh123 efflux was reached compared the control, indicating a substantial decrease of Rh123 efflux by ß-CD-SHs. Furthermore, it was observed that ß-CD-SHs led to a decrease in the reactivity of fluorescence-labeled anti-P-gp, suggesting additional effects on the conformation of P-gp. Overall, this study demonstrates the potential of ß-CD-SHs as effective modulator of P-gp-mediated drug efflux in Caco-2 cells.

Ocular antibacterial chitosan-maleic acid hydrogels: In vitro and in vivo studies for a promising approach with enhanced mucoadhesion.

The aim was to design and evaluate a chitosan-based conjugate providing high mucoadhesiveness and antibacterial activity for ocular infections treatment. Chitosan was conjugated with maleic acid via amide bond formation and infrared spectroscopy. Furthermore, 2,4,6-Trinitrobenzene sulfonic acid (TNBS) allowed characterization and quantification of conjugated groups, respectively. Biocompatibility was tested via hemolysis assay and Hen's Egg-Chorioallantoic membrane test. Characterization of the pH and osmolarity of hydrogels was followed by mucoadhesion assessment utilizing rheology. In addition, antibacterial studies were carried out towards Escherichia coli by broth microdilution test and agar-disk diffusion assay. In vivo studies were carried out following the already established Draize test and determining pharmacokinetic profile of dexamethasone in aqueous humour. The conjugate exhibited a degree of modification of 50.05 % and no toxicity or irritability. Moreover, mucoadhesive properties were enhanced in 2.68-fold and 1.81-fold for elastic and viscous modulus, respectively. Furthermore, rheological synergism revealed the presence of a gel-like structure. Additionally, broth microdilution and agar disk diffusion studies exhibited enhancement in antibacterial activity. Finally, in vivo studies manifested that hydrogels were highly tolerated, evidencing promising characteristics of the developed conjugate. The conjugate presented promising antimicrobial, long lasting mucoadhesive features and highly improved pharmacokinetics, leading to a revolutionizing approach in the treatment of ocular bacterial infections.

Charge-Reversible Nanoparticles: Advanced Delivery Systems for Therapy and Diagnosis.

The past two decades have witnessed a rapid progress in the development of surface charge-reversible nanoparticles (NPs) for drug delivery and diagnosis. These NPs are able to elegantly address the polycation dilemma. Converting their surface charge from negative/neutral to positive at the target site, they can substantially improve delivery of drugs and diagnostic agents. By specific stimuli like a shift in pH and redox potential, enzymes, or exogenous stimuli such as light or heat, charge reversal of NP surface can be achieved at the target site. The activated positive surface charge enhances the adhesion of NPs to target cells and facilitates cellular uptake, endosomal escape, and mitochondrial targeting. Because of these properties, the efficacy of incorporated drugs as well as the sensitivity of diagnostic agents can be essentially enhanced. Furthermore, charge-reversible NPs are shown to overcome the biofilm formed by pathogenic bacteria and to shuttle antibiotics directly to the cell membrane of these microorganisms. In this review, the up-to-date design of charge-reversible NPs and their emerging applications in drug delivery and diagnosis are highlighted.

PEGylated drug delivery systems in the pharmaceutical field: past, present and future perspective.

Target-site drug delivery systems are gaining interest in the pharmaceutical field due to their great advantages, such as higher drug dosing capacity and better bioavailability. However, some existing problems need to be overcome. An example, is the interaction between blood proteins and drug delivery systems. A potent candidate to approach the mentioned problem is based on polyethylene glycol (PEG) surface modifications. This polymer acts as a protector against the external possible interactions with other compounds, making targeted delivery possible. Diseases such as cancer, diabetes, hemophilia and pain treatment can benefit from these new systems. This review aims to give an overview of drug delivery systems based on PEGylation as surface modification as the pharmaceutical approach. Moreover, a deeper insight into the properties of PEG and its advantages is given, as well as a brief overview of present therapies based on this technology.

Allergies caused by textiles: control, research and future perspective in the medical field.

Textile production forms one of the most polluting industries worldwide. However, other than damaging environmental effects, chemical waste products, such as formaldehyde or thiazolinone, are problematic for human health, as allergic potential is present in these compounds. Mostly, contact dermatitis occurs when human skin is exposed to textiles. Moreover, non-eczemous variants are mainly associated to textiles. In order to diagnose the possible allergy of the patient towards these compounds, in vivo and in vitro methods ca be performed, such as patch testing or cytokine detection assays, respectively. Newest research focuses on medical textiles such as garments or sutures to help in diagnosis, therapy and recovery of the patients. Sutures and dressings with antimicrobial properties, with the release of oxygen and growth factors offer greater properties. In this review, state of the art in the field as well as future perspectives will be discussed, which are based on the smart textiles that are going to become more important and probably widespread after the current limits exceeded.

Current strategies to determine antifungal and antimicrobial activity of natural compounds.

Fungal and microbial infections are increasingly common diseases affecting not only humans, but also animals. Despite the fact that there are wide ranges of antifungal drugs that can be used as therapy against different types of mycosis, the large-scale needed for new antifungal and antimicrobial agents is undeniable. The reasons for a great demand for new agents are low effectiveness due to the development of resistance, host toxicity and various side effects of currently used therapeutics. In order to develop novel drugs against fungal infections, scientists need to search for new molecules that show antimicrobial activity. However, there are various methods to determine antifungal and antimicrobial activity such as diffusion methods, bioautography methods, dilution methods and other frequently used methods. This review aims to explain the methodologies mentioned, to highlight the functioning, usage, advantages and disadvantages and to compare the techniques using different sources of the last years. Additionally, some of the currently investigated natural compounds such as essential oils, which show promising results in the medication of fungal diseases, are mentioned.

Is hyaluronic acid the perfect excipient for the pharmaceutical need?

Hyaluronic acid has become an interesting and important polymer as an excipient for pharmaceutical products due to its beneficial properties, like solubility, biocompatibility and biodegradation. To improve the properties of hyaluronic acid, different possibilities for chemical modifications are presented, and the opportunities as novel systems for drug delivery are discussed. This review gives an overview over the production of hyaluronic acid, the possibilities of its chemical modification and the current state of in vitro and in vivo research. Furthermore, market approved and commercially available products are reviewed and derivatives undergoing clinical trials and applying for market approval are shown. In particular, hyaluronic acid has been studied for different administrations in rheumatology, ophthalmology, local anesthetics, cancer treatment and bioengineering of tissues. The present work concludes with perspectives for future administration of pharmaceuticals based on hyaluronic acid.

The progress on sulfhydryl modified polymers with regard to synthesis, characterization and mucoadhesion.

The concepts of mucoadhesion and mucoadhesive polymers were introduced in the 20th century, leading to several advantages. These included enhanced drug absorption and extended residence at specific site of action. Polymeric excipients underwent chemical modification with sulfhydryl groups on the polymeric backbone so as to improve mucoadhesive features as well as potential. This modification resulted in compounds mimicking the nature of secreted mucus glycoproteins. Thus, these thiol group-bearing excipients presented the ability to attach covalently to the mucosa by the disulfide bonding. Nevertheless, the first generation of these thiol-modified polymers, named thiomers, presented disadvantages such as low stability in aqueous media and/or the high susceptibility towards oxidation along with the drawback of low sufficient reactive functional moieties on the polymeric backbone at lower pH. Therefore, in the 21st century, a second generation of preactivated or S-protected polymers with protected thiol moieties were developed, as well as a third generation of thiomers, solving some of the previously described problems. This review article aimed to highlight the progess on a potent sulfhydryl modification during the last decades and the posterior characterization and in vitro/ex vivo/in vivo mucoadhesiveness.