Future Nanotechnology-Based Strategies for Improved Management of Helicobacter pylori Infection.

Helicobacter pylori (H. pylori) is a recalcitrant pathogen, which can cause gastric disorders. During the past decades, polypharmacy-based regimens, such as triple and quadruple therapies have been widely used against H. pylori. However, polyantibiotic therapies can disturb the host gastric/gut microbiota and lead to antibiotic resistance. Thus, simpler but more effective approaches should be developed. Here, some recent advances in nanostructured drug delivery systems to treat H. pylori infection are summarized. Also, for the first time, a drug release paradigm is proposed to prevent H. pylori antibiotic resistance along with an IVIVC model in order to connect the drug release profile with a reduction in bacterial colony counts. Then, local delivery systems including mucoadhesive, mucopenetrating, and cytoadhesive nanobiomaterials are discussed in the battle against H. pylori infection. Afterward, engineered delivery platforms including polymer-coated nanoemulsions and polymer-coated nanoliposomes are poposed. These bioinspired platforms can contain an antimicrobial agent enclosed within smart multifunctional nanoformulations. These bioplatforms can prevent the development of antibiotic resistance, as well as specifically killing H. pylori with no or only slight negative effects on the host gastrointestinal microbiota. Finally, the essential checkpoints that should be passed to confirm the potential effectiveness of anti-H. pylori nanosystems are discussed.

Potential anticancer activity of a new pro-apoptotic peptide-thioctic acid gold nanoparticle platform.

Targeted nanoparticle platforms designed to induce cell death by apoptosis can bypass the resistance mechanisms of cancer cells. With this in mind we have constructed a new cancer-targeting peptide-functionalized nanoparticle using gold nanoparticles (AuNPs) and a thioctic acid-DMPGTVLP peptide (TA-peptide) conjugate. Morphological analysis of the nanoparticles by transmission electron microscopy showed average diameters of about 3.52 nm and 26.2 nm for the AuNP core and shell, respectively. Strong affinity toward the nucleolin receptors of breast cancer cell lines MCF-7 and T47D was observed for the TA-peptide gold nanoparticles (TAP@AuNPs) based on IC50 values. Furthermore, the nanoparticles showed excellent hemocompatibility. Quantitative results of atomic absorption showed improved uptake of TAP@AuNPs. Treatment of the cells with TAP@AuNPS resulted in greater release of cytochrome c following caspase-3/7 activation compared with free TA-peptide. The cytosolic level of adenosine triphosphate for TAP@AuNPs was higher than in controls. Higher anti-tumor efficiency was observed for TAP@AuNPs than TA-peptide compared with phosphate-buffered saline after intratumoral injection in tumor-bearing mice. It can be concluded that the design and development of a receptor-specific peptide-AuNP platform will be valuable for theranostic applications in cancer nanomedicine.

Biomaterials coated with zwitterionic polymer brush demonstrated significant resistance to bacterial adhesion and biofilm formation in comparison to brush coatings incorporated with antibiotics.

A critical problem with the use of biomaterial implants is associated with bacterial adhesion on the surface of implants and in turn the biofilm formation. Among different strategies that have been reported to resolve this dilemma, surface design combined with both antiadhesive and antimicrobial properties has proven to be highly effective. Physiochemical properties of polymer brush coatings possess non-adhesive capability against bacterial adhesion and create a niche for further functionalization. The current study aims to evaluate the effect of antibiotics incorporated into the polymer brush on bacterial adhesion and biofilm formation. Brushes made of zwitterionic polymers were synthesized, functionalized with vancomycin via both physical and chemical conjugation, and grafted onto the silicon rubber surfaces. Antibacterial and antiadhesive measurements of designed coated biomaterials were mediated through the use of a parallel plate flow chamber against biofilm growth developed by Staphylococcus aureus and Escherichia coli over a period of 24 h. The analysis of biofilm growth on designed coated biomaterials showed that the pristine coated zwitterionic brushes are significantly resistant to bacterial adhesion and biofilm formation but not in the polymer brush coating incorporated with antibiotics.

A doxycycline-loaded microfiber of poly-metformin/PCL for eradicating melanoma stem cells.

Nowadays, electrospun fibrous mats are used as drug delivery systems for loading of potential drugs in order to kill cancer cells. In the study, a skin patch for treating melanoma cancer after surgery was made using polycaprolactone and polymetformin microfibers that were loaded with doxycycline (PolyMet/PCL@DOX), an anti-cancer stem cell agent. The morphology, structure, mechanical characteristics, swelling, and porosity of the electrospun microfibers were examined. Drug release andanticancereffectiveness of PolyMet/PCL@DOXwas evaluated against A375 melanoma cancer stem cells using the MTS, Flow cytometry, colony formation and CD44 expression assays. Scanning electron microscopy (SEM) verified the micro fibrous structure with a diameter of about 2.31 µm. The porosity and swelling percentages for microfibers was 73.5 % and 2.9 %, respectively. The tensile strength at the breaking point was equal to 3.84 MPa. The IC50 of PolyMet/PCL@DOX was 7.4 µg/mL. The survival rate of A375 cells after 72 h of PolyMet/PCL@DOX treatment was 43.9 %. The colony formation capacity of A375 cells decreased after PolyMet/PCL@DOX treatment. The level of CD44 expression in the PolyMet/PCL@DOX group decreased compared to the control group. Generally, PolyMet/PCL@DOX microfibers can be a promising candidate as a patch after surgery to eradicate cancer stem cells, effectively.

Synthesis of magnetic electroactive nanomotors based on sodium alginate/chitosan and investigation the influence of the external electric field on the mechanism of locomotion.

In this paper, we report a novel electric-driven Janus nanomotor (JNMs) based on SPIONs nanoparticle decorated with chitosan (Cs) and sodium alginate (Na/Alg) using the Pickering emulsion method. The JNMs dispersed in aqueous media exhibit linear trajectories under DC electric field, and the driving force is attributed to the self-electro-osmotic mechanism and surface modifications. This study offers an approach to remotely control the motion modes of the JNMs, including start, stop, directional and programmable motion, which can be advantageous for various application scenarios. The diffusion coefficient and velocity of the JNMs were investigated through mean square displacement analysis for single particle of JNMs, both in distilled water and in the presence of different di and trivalent metal cations (Fe3+, Al3+, Ba2+, Ca2+ and Mg2+) as crosslinking agents, as well as monovalent salts (LiCl and KCl). The results revealed that the motion of JNMs was fastest in the presence of Fe3+ as crosslinker agent (about 7.2181 µm2/s) due to its higher charge than equimolar Na+ . Moreover, it was demonstrated that increasing the ionic strength led to relatively higher speeds of JNMs, as the solution polarity increased and, as a result, the driving force of electro-osmoesis enhanced.

Synthesis of Fe-Doped Peroxidase Mimetic Nanozymes from Natural Hemoglobin for Colorimetric Biosensing and In Vitro Anticancer Effects.

Despite their efficiency and specificity, the instability of natural enzymes in harsh conditions has inspired researchers to replace them with nanomaterials. In the present study, extracted hemoglobin from blood biowastes was hydrothermally converted to catalytically active carbon nanoparticles (BDNPs). Their application as nanozymes for the colorimetric biosensing of H2O2 and glucose and selective cancer cell-killing ability was demonstrated. Particles that were prepared at 100 °C (BDNP-100) showed the highest peroxidase mimetic activity, with Michaelis-Menten constants (Km) of 11.8 mM and 0.121 mM and maximum reaction rates (Vmax) of 8.56 × 10-8 mol L-1 s-1 and 0.538 × 10-8 mol L-1 s-1, for H2O2 and TMB, respectively. The cascade catalytic reactions, catalyzed by glucose oxidase and BDNP-100, served as the basis for the sensitive and selective colorimetric glucose determination. A linear range of 50-700 µM, a response time of 4 min, a limit of detection (3σ/N) of 40 µM, and a limit of quantification (10σ/N) of 134 µM was achieved. In addition, the reactive oxygen species (ROS)-generating ability of BDNP-100 was employed for evaluating its potential in cancer therapy. Human breast cancer cells (MCF-7), in the forms of monolayer cell cultures and 3D spheroids, were studied by MTT, apoptosis, and ROS assays. The in vitro cellular experiments showed dose-dependent cytotoxicity of BDNP-100 toward MCF-7 cells in the presence of 50 µM of exogenous H2O2. However, no obvious damage was induced to normal cells in the same experimental conditions, verifying the selective cancer cell-killing ability of BDNP-100.

Additive Manufacturing of an Extended-Release Tablet of Tacrolimus.

An extended-release tablet of tacrolimus as once-daily dosing was fabricated using 3D printing technology. It was developed by combining two 3D-printing methods in parallel. Indeed, an optimized mixture of PVA, sorbitol, and magnesium stearate as a shell compartment was printed through a hot-melt extrusion (HME) nozzle while an HPMC gel mixture of the drug in the core compartment was printed by a pressure-assisted micro-syringe (PAM). A 3D-printed tablet with an infill of 90% was selected as an optimized formula upon the desired dissolution profile, releasing 86% of the drug at 12 h, similar to the commercial one. The weight variation, friability, hardness, assay, and content uniformity determination met USP requirements. A microbial evaluation showed that the 3D-printed tablet does not support microbial growth. SEM analysis showed smooth surfaces with multiple deposited layers. No peak interference appeared based on FTIR analysis. No decomposition of the polymer and drug was observed in the printing temperature, and no change in tacrolimus crystallinity was detected based on TGA and DSC analyses, respectively. The novel, sTable 3D-printed tablet, fabricated using controllable additive manufacturing, can quickly provide tailored dosing with specific kinetic release for personalized medicine at the point-of-care.

Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori.

INTRODUCTION: Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED: In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION: For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).

The Potential Use of Antibiotics Against Helicobacter pylori Infection: Biopharmaceutical Implications.

Helicobacter pylori (H. pylori) is a notorious, recalcitrant and silent germ, which can cause a variety of debilitating stomach diseases, including gastric and duodenal ulcers and gastric cancer. This microbe predominantly colonizes the mucosal layer of the human stomach and survives in the inhospitable gastric microenvironment, by adapting to this hostile milieu. In this review, we first discuss H. pylori colonization and invasion. Thereafter, we provide a survey of current curative options based on polypharmacy, looking at pharmacokinetics, pharmacodynamics and pharmaceutical microbiology concepts, in the battle against H. pylori infection.