Insight in Superiority of the Hydrophobized Gentamycin in Terms of Antibiotics Delivery to Bone Tissue.

Bone infections are a serious problem to cure, as systemic administration of antibiotics is not very effective due to poor bone vascularization. Therefore, many drug delivery systems are investigated to solve this problem. One of the potential solutions is the delivery of antibiotics from poly(L-actide-co-glycolide) (PLGA) nanoparticles suspended in the gellan gum injectable hydrogel. However, the loading capacity and release kinetics of the system based on hydrophilic drugs (e.g., gentamycin) and hydrophobic polymers (e.g., PLGA) may not always be satisfying. To solve this problem, we decided to use hydrophobized gentamycin obtained by ion-pairing with dioctyl sulfosuccinate sodium salt (AOT). Herein, we present a comparison of the PLGA nanoparticles loaded with hydrophobic or hydrophilic gentamycin and suspended in the hydrogel in terms of physicochemical properties, drug loading capacity, release profiles, cytocompatibility, and antibacterial properties. The results showed that hydrophobic gentamycin may be combined in different formulations with the hydrophilic one and is superior in terms of encapsulation efficiency, drug loading, release, and antibacterial efficacy with no negative effect on the NPs morphology or hydrogel features. However, the cytocompatibility of hydrophobic gentamycin might be lower, consequently more extensive study on its biological properties should be provided to evaluate a safe dose.

Composites Based on Gellan Gum, Alginate and Nisin-Enriched Lipid Nanoparticles for the Treatment of Infected Wounds.

Due to growing antimicrobial resistance to antibiotics, novel methods of treatment of infected wounds are being searched for. The aim of this research was to develop a composite wound dressing based on natural polysaccharides, i.e., gellan gum (GG) and a mixture of GG and alginate (GG/Alg), containing lipid nanoparticles loaded with antibacterial peptide-nisin (NSN). NSN-loaded stearic acid-based nanoparticles (NP_NSN) were spherical with an average particle size of around 300 nm and were cytocompatible with L929 fibroblasts for up to 500 µg/mL. GG and GG/Alg sponges containing either free NSN (GG + NSN and GG/Alg + NSN) or NP_NSN (GG + NP_NSN and GG/Alg + NP_NSN) were highly porous with a high swelling capacity (swelling ratio above 2000%). Encapsulation of NSN within lipid nanoparticles significantly slowed down NSN release from GG-based samples for up to 24 h (as compared to GG + NSN). The most effective antimicrobial activity against Gram-positive Streptococcus pyogenes was observed for GG + NP_NSN, while in GG/Alg it was decreased by interactions between NSN and Alg, leading to NSN retention within the hydrogel matrix. All materials, except GG/Alg + NP_NSN, were cytocompatible with L929 fibroblasts and did not cause an observable delay in wound healing. We believe that the developed materials are promising for wound healing application and the treatment of bacterial infections in wounds.

Poly(amidoamine) Dendrimers as Nanocarriers for 5-Fluorouracil: Effectiveness of Complex Formation and Cytotoxicity Studies.

Two generations of positively charged poly(amidoamine) dendrimers (PAMAMs) were selected for study as potential carriers for the anticancer drug 5-fluorouracil (5FU), a drug primarily used in the treatment of colorectal cancer. Analytical techniques, such as UV-Vis spectrophotometry, NMR Spectroscopy and Laser Doppler Velocimetry (LDV), have shown that the most critical factor determining the formation of a PAMAM-5FU complex is the starting components' protonation degree. The tests confirmed the system's ability to attach about 20 5FU molecules per one dendrimer molecule for the G4PAMAM dendrimer and about 25 molecules for the G6PAMAM dendrimer, which gives a system yield of 16% for the fourth generation and 5% for sixth generation dendrimers. Additionally, using the QCM-D method, the adsorption efficiency and the number of drug molecules immobilized in the dendrimer structure were determined. A new aspect in our study was the determination of the change in zeta potential (ζ) induced by the immobilization of 5FU molecules on the dendrimer's outer shell and the importance of this effect in the direct contact of the carrier with cells. Cytotoxicity tests (resazurin reduction and MTS tests) showed no toxicity of dendrimers against mouse fibroblast cells (L929) and a significant decrease in cell viability in the case of four human malignant cell lines: malignant melanoma (A375), glioblastoma (SNB-19), prostate cancer (Du-145) and colon adenocarcinoma (HT-29) during incubation with PAMAM-5FU complexes. The purpose of our work was to investigate the correlation between the physicochemical properties of the carrier and active substance and the system efficiency and optimizing conditions for the formation of an efficient system based on PAMAM dendrimers as nanocarriers for 5-fluorouracil. An additional aspect was to identify potential application properties of the complexes, as demonstrated by cytotoxicity tests.

Inhalable microparticles as drug delivery systems to the lungs in a dry powder formulations.

Inhalation-administrated drugs remain an interesting possibility of addressing pulmonary diseases. Direct drug delivery to the lungs allows one to obtain high concentration in the site of action with limited systemic distribution, leading to a more effective therapy with reduced required doses and side effects. On the other hand, there are several difficulties in obtaining a formulation that would meet all the criteria related to physicochemical, aerodynamic and biological properties, which is the reason why only very few of the investigated systems can reach the clinical trial phase and proceed to everyday use as a result. Therefore, we focused on powders consisting of polysaccharides, lipids, proteins or natural and synthetic polymers in the form of microparticles that are delivered by inhalation to the lungs as drug carriers. We summarized the most common trends in research today to provide the best dry powders in the right fraction for inhalation that would be able to release the drug before being removed by natural mechanisms. This review article addresses the most common manufacturing methods with novel modifications, pros and cons of different materials, drug loading capacities with release profiles, and biological properties such as cytocompatibility, bactericidal or anticancer properties.

The Effect of Chitosan on Physicochemical Properties of Whey Protein Isolate Scaffolds for Tissue Engineering Applications.

New scaffolds, based on whey protein isolate (WPI) and chitosan (CS), have been proposed and investigated as possible materials for use in osteochondral tissue repair. Two types of WPI-based hydrogels modified by CS were prepared: CS powder was incorporated into WPI in either dissolved or suspended powder form. The optimal chemical composition of the resulting WPI/CS hydrogels was chosen based on the morphology, structural properties, chemical stability, swelling ratio, wettability, mechanical properties, bioactivity, and cytotoxicity evaluation. The hydrogels with CS incorporated in powder form exhibited superior mechanical properties and higher porosity, whereas those with CS incorporated after dissolution showed enhanced wettability, which decreased with increasing CS content. The introduction of CS powder into the WPI matrix promoted apatite formation, as confirmed by energy dispersive spectroscopy (EDS) and Fourier transform infrared spectroscopy (FTIR) analyses. In vitro cytotoxicity results confirmed the cytocompatibility of CS powder modified WPI hydrogels, suggesting their suitability as cell scaffolds. These findings demonstrate the promising potential of WPI/CS scaffolds for osteochondral tissue repair.

Betalains isolated from underexploited wild plant Atriplex hortensis var. rubra L. exert antioxidant and cardioprotective activity against H9c2 cells.

Atriplex hortensis var. rubra L. extracts prepared from leaves, seeds with sheaths, and stems were characterized for betalainic profiles by spectrophotometry, LC-DAD-ESI-MS/MS and LC-Orbitrap-MS techniques. The presence of 12 betacyanins in the extracts was strongly correlated with high antioxidant activity measured by ABTS, FRAP, and ORAC assays. Comparative assessment between samples indicated the highest potential for celosianin and amaranthin (IC50 21.5 and 32.2 µg/ml, respectively). The chemical structure of celosianin was elucidated for the first time by complete 1D and 2D NMR analysis. Our findings also demonstrate that betalain-rich A. hortensis extracts and purified pigments (amaranthin and celosianin) do not induce cytotoxicity in a wide concentration range in rat cardiomyocytes model (up to 100 µg/ml for extracts and 1 mg/ml for pigments). Furthermore, tested samples effectively protect H9c2 cells from H2O2-induced cell death and prevent from apoptosis induced by Paclitaxel. The effects were observed at sample concentrations between 0.1 and 10 µg/ml.

Poly(sebacic acid) microparticles loaded with azithromycin as potential pulmonary drug delivery system: Physicochemical properties, antibacterial behavior, and cytocompatibility studies.

Recurrent bacterial infections are a common cause of death for patients with cystic fibrosis and chronic obstructive pulmonary disease. Herein, we present the development of the degradable poly(sebacic acid) (PSA) microparticles loaded with different concentrations of azithromycin (AZ) as a potential powder formulation to deliver AZ locally to the lungs. We characterized microparticle size, morphology, zeta potential, encapsulation efficiency, interaction PSA with AZ and degradation profile in phosphate buffered saline (PBS). The antibacterial properties were evaluated using the Kirby-Bauer method against Staphylococcus aureus. Potential cytotoxicity was evaluated in BEAS-2B and A549 lung epithelial cells by the resazurin reduction assay and live/dead staining. The results show that microparticles are spherical and their size, being in the range of 1-5 µm, should be optimal for pulmonary delivery. The AZ encapsulation efficiency is nearly 100 % for all types of microparticles. The microparticles degradation rate is relatively fast - after 24 h their mass decreased by around 50 %. The antibacterial test showed that released AZ was able to successfully inhibit bacteria growth. The cytotoxicity test showed that the safe concentration of both unloaded and AZ-loaded microparticles was equal to 50 µg/ml. Thus, appropriate physicochemical properties, controlled degradation and drug release, cytocompatibility, and antibacterial behavior showed that our microparticles may be promising for the local treatment of lung infections.