Title: Investigation of Antioxidant, Antibacterial and Photocatalytic Activities of Silver Nanoparticles Synthesized via Sebin Walnut Fruit Extract

Abstract

The origin of walnut samples used in this study is Çakır Village, Çileder neighborhood, Şebinkarahisar district, Giresun Province, Türkiye. Having a total tocopherol content of 36.3% plays a major role in the enhanced antioxidant properties of Sebin walnut. When the tocopherol content of 100 g oil obtained from Sebin walnut was examined, the total amount of tocopherol was 36.9 mg, of which 1.4 mg α-Tocopherol, 33.1 mg γ + β-Tocopherol, 2.4 mg δ-Tocopherol were determined. In our study, we extracted Sebin walnut (Juglans Regia) fruits by pestling in the mortar and filtered. We used the walnut fruit exract for reducing to Ag+ to Ag0. UV-vis, FT-IR, DLS, SEM, EDAX and TEM characterization studies were carried out in order to find out whether synthesized silver nanoparticles (AgNPs) can really be synthesized, the functional groups and bond structures of AgNPs, the particle sizes of AgNPs, the zeta potential of AgNPs, the surface morphology of AgNPs, the percentage distribution of the elements contained in AgNPs. AgNPs showed promising antioxidant properties via DPPH radical scavenging and Folin-Ciocalteu methods. The antibacterial effects of AgNPs were observed against to liquid and solid forms of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Also obtained AgNPs showed promising photocatalytic activity on the photodegradation of Methylene Blue dye.

Results/Conclusion/Images:

Synthesized AgNP showed a peak at 235 nm which is characteristic to AgNP at UV-vis spectrum [1-5]. The FT-IR spectrum of AgNPs shows a strong band at 3212,826 cm-1 indicating the presence of hydroxyl functional groups that may belong to polyphenols and another band at 1631,48 cm-1 against C-N and C-C stretching indicating the presence of protein [6,7]. According to DLS analyses, the average particle size of the synthesised AgNPs was determined as 40.92 nm and the zeta potential value as -24 mV and these reults are compatible with the previous studies [8,9]. According to SEM images, it was determined that the synthesised AgNPs were spherical particles and the average particle size of these particles was 34.6 nm that is compatible with previous studies [10]. As a result of EDAX analysis of AgNPs, the dominant elements were 28.53% silver (Ag), 4.76% copper (Cu), 17.59% oxygen (O) and 49.13% carbon (C) and these reults are compatible with previous studies [11]. According to TEM images, the synthesised AgNPs were found to be spherical and the average particle size was determined as 18,191 nm and this result is supported by the previous studies [12-15]. According to Folin-Ciocalteu method results, the excellent correlation coefficient (R2) value was found to be as 0.9921 for AgNPs obtained from Sebin Walnut Fruit Extract. When the amount of AgNPs was increased 3 times, DPPH concentration decreased by 24.76%. The addition of 100 ml of M-AgNPs decreased the concentration of DPPH radical by 43.7 mg/l. For the liquid bacteria cultures, a 32.23% and 11.62% decrease was observed in the bacterial concentration of E.coli to which 1.2 and 2.4 ml of M-AgNP was added, respectively. A 2.671%, 14.17%, 2.15%, 18.38%, 0.444% and 12.52% decrease was observed in the bacterial concentration of S. aureus to which 0.6, 0.9, 1.2, 1.5, 2.1, 2.4 ml AgNP was added, respectively. In liquid form E.coli, bacterial deaths were observed in areas of 0.45, 0.63, 0.63, 0.45, 0.45, 0.283, 0.45 and 0.45 cm2 as a result of AgNP added in amounts of 0.6, 0.9, 1.2, 1.5, 1.8, 2.1 and 2.4 ml, respectively. The optimum amounts of AgNP for E.coli were 0.9 and 1.2 ml. In liquid form of S.aureus, bacterial deaths were observed in areas of 1.04, 1.04, 0.83, 1.04, 0.83, 0.83, 0.83 and 0.283 cm2 as a result of AgNP added in amounts of 0.6, 0.9, 1.2, 1.5, 1.8, 2.1 and 2.4 ml, respectively. The optimum amounts of AgNP for S.aureus were determined as 0.6, 0.9 and 1.5 ml. As a result of the degradation test with methylene blue, the intensity of the characteristic peak at 664 nm decreased by 33.77% 12 hours after the addition of AgNP.

Title: Human Nanomaterials in The Clinic

Abstract

Nanomaterials have been widely tested in vitro and in small order animal studies for decades (Figure 1). Results have shown greater tissue growth, decreased bacteria growth, and inhibited inflammation. However, few studies exist examining human tissue response to nanomaterials. This presentation presents a cohort study of nano implants inserted into humans. In particular, one study includes the implantation of nanotextured spinal implants into over 14,000 patients over the past 5 years. Results demonstrated no cases of infections or other implant failures which is significantly better than statistics on conventional spinal implants which have up to 20% failure rates. This study will further explain that nano implants mimic the natural nano texture of bone itself and possess surface energy that can competitively increase the adsorption of proteins known to promote osteoblast (bone forming cells) functions, decrease bacteria functions, and limit inflammatory cell functions. As such, this presentation will cover the few human clinical studies on nano implants showing improved human health.

Results/Conclusion/Images:

Figure 1: Nanometer Pores Through a Ti Orthopedic Implant

Title: Polymer Composites for Advanced Drug Delivery: Current Developments and Future Perspective

Abstract

Polymer composites have emerged as promising drug delivery materials owing to their unique features, including excellent biocompatibility, biodegradability, and customizable drug release kinetics. Due to their capacity to improve drug solubility, bioavailability, and targeting efficiency, polymer composites have attracted substantial attention in recent years as a drug delivery method. This article presents a comprehensive overview of the applications of polymer composites in pharmaceutical and drug delivery systems. Natural polymer composites, synthetic polymer composites, and hybrid polymer composites are among the polymer composites discussed in this article. The merits and disadvantages of each type of polymer composite are discussed, as well as their specialised applications in drug administration, such as sustained release formulations, targeted drug delivery, and implantable drug delivery devices. In addition, the paper addresses recent developments in polymer composite-based drug delivery systems, such as nanocomposites and 3D printing technologies. In addition, the study highlights the regulatory considerations for polymer compositebased drug delivery systems, such as safety and toxicity problems. In conclusion, polymer composites have shown significant promise for enhancing drug delivery and patient outcomes, and their continuous development and improvement are essential for the evolution of medicines.

Title: Spine Bracing: When to Utilize—A Narrative Review

Abstract

Spinal bracing is a common non-surgical technique that allows clinicians to prevent and correct malformations or injuries of a patient’s spinal column. This review will explore the current standards of practice on spinal brace utilization. Specifically, it will highlight bracing usage in traumatic injuries, pregnancy, pediatrics, osteoporosis, and hyperkyphosis; address radiological findings concurrent with brace usage; and provide an overview of the braces currently available and advancements in the field. In doing so, we aim to improve clinicians’ understanding and knowledge of bracing in common spinal pathologies to promote their appropriate use and improve patient outcomes.

Title: Development and Evaluation of Gastroretentive Floating Tablet Using 3d Printing Technology

Abstract

Three dimensional (3D) printing technologies has become a potential tool for the pharmaceutical sector, leading to personalized medicine focused on the patient’s needs. Individualized drug and dosage forms can be produce by using 3D printing for future therapeutic application. Herein, the aim of this study was to explore the feasibility of fused deposition modelling (FDM) 3D printing to prepare gastro-floating tablets of metronidazole. A nitro-imidazole class drug metronidazole, was chosen as a model drug to examine, and was successfully assembled into floating tablet case made up of commercial polyvinyl alcohol (PVA) filament. The tablet was designed by AutoCAD followed by slicing using Cura Ultimaker 4.4 software. The formulation conditions for preparation of 3D floating tablet case were optimized by observing different orifice. Three different batches were optimized on the basis of orifice size. The floating tablet case consists of body and cap as separate component at the bottom of the body of tablet case and an air chamber was designed at the inner top of cap. All the dimensions for the formulation were same only different orifice was optimized. These printed tablets were evaluated for weight variation, friability, hardness, in-vitro floating test, and in- vitro dissolution studies. All results were within acceptable range and 0.5 mm orifice case was floated on 0.1 N HCl media surface for more than 8hr and provided zero-order drug release with r 2 values of 0.9989. These data indicate that the current 3D printing tablet case has promise in the development of floating drug delivery systems.

Designing of Tablet Structure (Auto CAD)

Finishing of the Tablet After the Printing

Title: Green Synthesis and Characterization of Biogenic Silver nanoparticles (AgNPs) from Selected Medicinal Plants for their Pharmacological Potential

Abstract

The development of biosynthetic and environmentally friendly technologies for the production of nanomaterials has given rise to the field of bio nanotechnology. For millennia, the potent bactericidal effects of silver have been known. Silver (Ag) nanoparticles (NPs) were produced using various amounts of M. philippensis, R. indica, M. piperita, J. officinale, and P. granatum plant extracts at room temperature. The biological activities of the nanoparticles made using plant extracts from three to five important medicinal plants have been compared by the green synthesis of AgNPs utilizing plant extracts. Different microscopy and spectroscopic analyses were used to describe nanoparticles. The sizes and shapes of the biosynthesized AgNPs were shown to change with the concentration of plant extract when examined under an atomic force microscope (AFM), scanning electron microscope (SEM), X-ray diffractometer (XRD), and UV-vis spectrophotometer. Significant variations in the antibacterial activity of biologically produced AgNPs against two different gram-negative bacteria were seen prepared from plant extracts of the five different plants. Additionally, these findings reveal that the antibacterial and cytotoxic properties of AgNPs made from synthetic plant extract depend on their structure. In contrast to predominantly spherical nanoparticles, the nanoparticles of diverse shapes displayed the strongest antibacterial and cytotoxic activities. The current findings showed that the form of the nanoparticles and the origin of the plant extract employed in their manufacture had an impact on the biological activities of AgNPs. Furthermore, this study also provides a chemical free synthesis method to produce silver nanoparticles and provide a better approach to produce the nanoparticles which can be used for medical purposes.

Title: Biomimetic Hydrogels to Promote Wound Healing

Abstract

Chronic, non-healing diabetic wounds put a massive economic burden on health services causing patient incompliance and discomfort. Thorough interpreting of chronic wound pathophysiology led to the fabrication of targeted systems of drug delivery that can improve and accelerate the wound healing process. Bioploymers and regenerin based extract are now explored for the fabrication of wound dressings. Polysaccharides elicit enormous and promising applications due to their extensive obtainability, innocuousness, and biodegradability. Various outstanding features of polysaccharides can be employed to fabricate biomimetic and multifunctional hydrogels as efficient wound dressings. These hydrogels mimic the natural extracellular matrix and also boost the proliferation of cells.

The therapeutic effectiveness of the placenta can be well defined with respect to several biochemical mechanisms of various components present in it. The placental extract derived from biomedical wastes has also shown a great potential for treatment of various diseases. Placental therapy has been reported specifically to have potent action on treatment of diseases and tissue regeneration. Placental bioactive components and their multi-targeting identity prompted us to compile the précised information on placental extract products. However, some findings are needed to be explored by scientific community to prove their clinical potential with significant statistical validation. In the light of available information and the usefulness of the placental extract, it is necessary that the formulations of various desirable properties may be developed to meet the clinical requirements in several treatment paradigms. It is also a matter of exploration that the short- and long-term adverse effects to be explored by advanced scientific techniques.

Owing to distinctive architectures and abundance of biopolymer as well as placental extract based gel have exceptional physicochemical properties and unique therapeutic interventions. Hydrogels designed using them can effectively safeguard wounds from bacterial attack. More research is required to engineer multifaceted advanced hydrogels with tuneable and adjustable properties to attain huge potential in wound healing. Such hydrogels demonstrated better healing as they inhibited bacterial growth and expedited re-epithelization and cell proliferation. So, these hydrogels can be used for effective wound care offering truly valuable material in the field of wound healing and certainly opening new avenues for future research and development.

Results/Conclusion/Images:

Title: Designing free flowing dry Nano powder using Micro Reactor based thin film freezing technique.

Abstract

Free flowing characteristic of powder is important consideration in pharmaceuticals. The advancements in nanopowder technology is emerging with enhanced surface characteristics required for pharmaceutical products. Drying of nanopowder formulation is difficulty task and surface drying in considered to be important parameters for biosimilar, biological, pharmaceutical and good products. The drying is almost final stage of product development and has several challenges may possibly dismantle the characteristics of products if not screened properly. Generation of nanosize dispersion using microreactor technology followed by thin film freezing (TFF) pave a way out of new strategies for reshaping the existing products in newer forms. The advent of new technologies is helpful for the designing new products for direct commercialization. The microreactor technology also been helpful for surface engineering of nanomaterials useful for targeted drug delivery. The new advance technique not only increase surface characteristics but also improve the flow characteristics with smoothing process parameters. TFF holds promise in delivering therapeutics for lung diseases such as fungal infection, bacterial infection, lung dysfunction, and pneumonia..

Results/Conclusion/Images:

Surface engineering of nanopharmaceutics increases selectivity towards specified target with reducing dose and dosing frequency of conventional therapeutic agent. The modulated technique like microreactors supports upscaling of preparation at commercial scale with maintaining physicochemical characteristics of powder material. The use of TFF maintains the morphology suitable for surface interaction at biointerfaces. The microreactor technology increase encapsulation of therapeutic agent along with increase in dissolution characteristics. The TFF supports the improvement in the stability and protects the drug or biomolecules from degradation. The TFF is considered as advance technique and suitable for drying of vaccine, biosimilar, biotechnological products, etc. The present technology supports the continous manufacturing of pharmaceutcals.

Title: Novel Investigational Anti-Sars-Cov‑2 Agent Ensitrelvir “S-217622”: A Very Promising Potential Universal Broad-Spectrum Antiviral at The Therapeutic Frontline of Coronavirus Species

Abstract

Lately, nitrogenous heterocyclic antivirals, such as nucleoside-like compounds, oxadiazoles, thiadiazoles, triazoles, quinolines, and isoquinolines, topped the therapeutic scene as promising agents of choice for the treatment of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and their accompanying ailment, the coronavirus disease 2019 (COVID-19). At the same time, the continuous emergence of new strains of SARS-CoV-2, like the Omicron variant and its multiple sublineages, resulted in a new defiance in the enduring COVID-19 battle. Ensitrelvir (S-217622) is a newly discovered orally active noncovalent nonpeptidic agent with potential strong broad-spectrum anticoronaviral activities, exhibiting promising nanomolar potencies against the different SARS-CoV-2 variants. S-217622 effectively and nonspecifically hits the main protease (Mpro) enzyme of a broad scope of coronaviruses. Herein, in the present computational/biological study, we tried to extend these previous findings to prove the universal activities of this investigational agent against any coronavirus, irrespective of its type, through synchronously acting on most of its main unchanged replication enzymes/proteins, including (in addition to the Mpro), e.g., the highly conserved RNA-dependent RNA polymerase (RdRp) and 3′-to-5′ exoribonuclease (ExoN). Biochemical evaluation proved, using the in vitro anti-RdRp/ExoN bioassay, that S-217622 can potently inhibit the replication of coronaviruses, including the new virulent strains of SARS-CoV-2, with extremely minute in vitro anti-RdRp and anti-RdRp/ExoN half-maximal effective concentration (EC50) values of 0.17 and 0.27 μM, respectively, transcending the anti-COVID-19 drug molnupiravir. The preliminary in silico results greatly supported these biochemical results, proposing that the S-217622 molecule strongly and stabilizingly strikes the key catalytic pockets of the SARS-CoV-2 RdRp’s and ExoN’s principal active sites predictably via the nucleoside analogism mode of anti-RNA action (since the S-217622 molecule can be considered as a uridine analog). Moreover, the idealistic druglikeness and pharmacokinetic characteristics of S-217622 make it ready for pharmaceutical formulation with the expected very good clinical behavior as a drug for the infections caused by coronaviruses, e.g., COVID-19. To cut it short, the current critical findings of this extension work significantly potentiate and extend the S-217622’s previous in vitro/in vivo (preclinical) results since they showed that the striking inhibitory activities of this novel anti-SARS-CoV-2 agent on the Mpro could be extended to other replication enzymes like RdRp and ExoN, unveiling the possible universal use of the compound against the next versions of the virus (i.e., disclosing the nonspecific anticoronaviral properties of this compound against almost any coronavirus strain), e.g., SARS-CoV-3, and encouraging us to rapidly start the compound’s vast clinical anti-COVID-19 evaluations.

Title: Enhanced Efficacy of Photodynamic Therapy When Combined with Nitroglyc­ErinOintment Administration On Xenografted Retinoblastoma in Mice

Abstract

The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamictherapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on nude mice.

PDT uses a non-mutagen photosensitizing agent (PS: glycoconjugated porphyrin derivative) activated by red light exposure. Absorption of light initiates photochemical reactions leading to the generation of cytotoxic photoproducts (ROSs: oxygen reactive species) responsible for the therapeutic effects. We propose to increase the PDT efficiency (on our least responsive retinoblastoma line to treatment) with a better PS delivery in the tumor generated by NG which is known to dilate vessels and enhance the permeability and retention (EPR) of macromolecules in solid tumors.

Methods: In vivo follow-up of the therapeutic effects was performed by sodium MRI which directly monitors variations of sodium concentrations in a non-invasive way and can be used to follow-up the tumor response to therapy. NG ointment was applied one hour before PDT. The PDT protocol implied a double tumor targeting, cellular and vascular. A first PS dose was injected followed by a second one, separated by a 3 h interval. The time lapse allowed the PS molecules to penetrate into tumor cells. Ten minutes after the second dose, the PS was red light activated using a laser.

Results: The PDT efficacy (increase of necrosis, decrease of the tumor volume) was enhanced by applying NG ointment on the skin of tumor-bearing animals.

Conclusion: NG increases the PDT efficacy by enhancing the intratumor concentration of PS inducing a more significant production of ROSs on the illuminated region increasing thus the propagation of cellular death signalling deeper into the tumor (bystander effect).