Advances in nucleic acid delivery strategies for diabetic wound therapy.

In recent years, the prevalence of diabetic wounds has significantly increased, posing a substantial medical challenge due to their propensity for infection and delayed healing. These wounds not only increase mortality rates but also lead to amputations and severe mobility issues. To address this, advancements in bioactive molecules such as genes, growth factors, proteins, peptides, stem cells, and exosomes into targeted gene therapies have emerged as a preferred strategy among researchers. Additionally, the integration of photothermal therapy (PTT), nucleic acid, and gene therapy, along with 3D printing technology and the layer-by-layer (LBL) self-assembly approach, shows promise in diabetic wound treatment. Effective delivery of small interfering RNA (siRNA) relies on gene vectors. This review provides an in-depth exploration of the pathophysiological characteristics observed in diabetic wounds, encompassing diminished angiogenesis, heightened levels of reactive oxygen species, and impaired immune function. It further examines advancements in nucleic acid delivery, targeted gene therapy, advanced drug delivery systems, layer-by-layer (LBL) techniques, negative pressure wound therapy (NPWT), 3D printing, hyperbaric oxygen therapy, and ongoing clinical trials. Through the integration of recent research insights, this review presents innovative strategies aimed at augmenting the multifaceted management of diabetic wounds, thus paving the way for enhanced therapeutic outcomes in the future.

Development and characterization of ferulic acid-loaded chitosan nanoparticle embedded- hydrogel for diabetic wound delivery.

Diabetic wounds present a significant global health challenge exacerbated by chronic hyperglycemia-induced oxidative stress, impeding the natural healing process. Despite various treatment strategies, diabetic foot ulceration lacks standardized therapy. Ferulic acid (FA), known for its potent antidiabetic and antioxidant properties, holds promise for diabetic wound management. However, oral administration of FA faces limitations due to rapid oxidation, stability issues, and low bioavailability. The topical application of FA-loaded chitosan nanoparticles (FA-CSNPs) has emerged as a promising approach to overcome these challenges. Here, we report the development of a sustained-release formulation of FA-CSNPs within a hydrogel matrix composed of Chitosan and gelatin. The FA-CSNPs were synthesized using the ionic gelation method andoptimized through a Central Composite Design (CCD) approach. Characterization of the optimized nanoparticles revealed spherical morphology, a particle size of 56.9 ± 2.5 nm, and an impressive entrapment efficiency of 90.3 ± 2.4 %. Subsequently, an FA-CSNPs-loaded hydrogel was formulated, incorporating chitosan as a gelling agent, gelatin to enhance mechanical properties and cell permeation, and glutaraldehyde as a cross-linker. Comprehensive characterization of the hydrogel included pH, moisture loss, porosity, swelling index, rheology, water vapor transmission rate (WVTR), SEM, TEM, invitro drug release studies, antioxidant activity, antibacterial efficacy, cell cytotoxicity, cell migration studies on L929 fibroblast cell line, and stability studies. The stability study demonstrated negligible variations in particle size, zeta potential, and entrapment efficiency over 60 days, ensuring the stable nature of nanoparticles and hydrogel. This innovative delivery approach embedded within a hydrogel matrix holds significant promise for enhancing the therapeutic efficacy of FA-CSNPs-hydrogel in diabetic wound healing applications.

Emerging Trends in Hybrid Nanoparticles: Revolutionary Advances and Promising Biomedical Applications.

Modern nanostructures must fulfill a wide range of functions to be valuable, leading to the combination of various nano-objects into hierarchical assemblies. Hybrid Nanoparticles (HNPs), comprised of multiple types of nanoparticles, are emerging as nanoscale structures with versatile applications. HNPs offer enhanced medical benefits compared to basic combinations of distinct components. They address the limitations of traditional nanoparticle delivery systems, such as poor water solubility, nonspecific targeting, and suboptimal therapeutic outcomes. HNPs also facilitate the transition from anatomical to molecular imaging in lung cancer diagnosis, ensuring precision. In clinical settings, the selection of nanoplatforms with superior reproducibility, cost-effectiveness, easy preparation, and advanced functional and structural characteristics is paramount. This study aims toextensively examine hybrid nanoparticles, focusing on their classification, drug delivery mechanisms, properties of hybrid inorganic nanoparticles, advancements in hybrid nanoparticle technology, and their biomedical applications, particularly emphasizing the utilization of smart hybrid nanoparticles. PHNPs enable the delivery of numerous anticancer, anti-leishmanial, and antifungal drugs, enhancing cellular absorption, bioavailability, and targeted drug delivery while reducing toxic side effects.

COVID-19: Recent Insight in Genomic Feature, Pathogenesis, Immunological Biomarkers, Treatment Options and Clinical Updates on SARS-CoV-2.

SARS-CoV-2 is a highly contagious and transmissible viral infection that first emerged in 2019 and since then has sparked an epidemic of severe respiratory problems identified as "coronavirus disease 2019" (COVID-19) that causes a hazard to human life and safety. The virus developed mainly from bats. The current epidemic has presented a significant warning to life across the world by showing mutation. There are different tests available for testing Coronavirus, and RT-PCR is the best, giving more accurate results, but it is also time-consuming. There are different options available for treating n-CoV-19, which include medications such as Remdesivir, corticosteroids, plasma therapy, Dexamethasone therapy, etc. The development of vaccines such as BNT126b2, ChAdOX1, mRNA-1273 and BBIBP-CorV has provided great relief in dealing with the virus as they decreased the mortality rate. BNT126b2 and ChAdOX1 are two n-CoV vaccines found to be most effective in controlling the spread of infection. In the future, nanotechnology-based vaccines and immune engineering techniques can be helpful for further research on Coronavirus and treatment of this deadly virus. The existing knowledge about the existence of SARS-CoV-2, along with its variants, is summarized in this review. This review, based on recently published findings, presents the core genetics of COVID-19, including heritable characteristics, pathogenesis, immunological biomarkers, treatment options and clinical updates on the virus, along with patents.

In silico exploration of venlafaxine, a potential non-tricyclic antidepressant in a liposomal formulation for nose-to-brain drug delivery.

OBJECTIVE: Non-tricyclic antidepressants (non-TCAs) work by preventing the intake of norepinephrine and serotonin. Therefore, the aim of this study was to identify a potent non-TCAs and to develop liposomal formulation, characterize and to determine the drug release study across model of dialysis membrane via in vitro and in silico techniques. METHODS: The in silico docking analysis identified venlafaxine (VLF) as the best non-TCAs with the depressant targets (PDB ID: 3PBL and 4BVN). VLF-loaded liposomal formulation was prepared by the thin-film hydration technique and characterized by physicochemical properties, including entrapment efficacy, in vitro drug release, particle size analysis, and FTIR. Moreover, this article also compares VLF and VLF-loaded with liposome carriers (LPs) based on nose-to-brain drug delivery approaches to treating depression. RESULTS: Drug release profiles of the optimal liposomal formulation of VLF-LPs were examined in the high entrapment efficiency 94.13 ± 1.20% was attained at 224 nm, composed of spherical particles having a mean particle size of 191 ± 2.0 nm, a polydispersity index of 0.281 ± 0.06 and zeta potential of -20.3 mV. The best formulation of VLF-LPs was more effective than oral VLF treatment, as shown by the in vitro drug release data. CONCLUSION: The results show that the VLF-LPs formulation is a promising potential platform for application in nose-to-brain drug delivery. Thus, highlighting the robustness of the intranasal drug delivery system with enhanced pharmaceutical properties, efficacy, and bioavailability for the anti-depression effect.

Advanced Drug Delivery System for Management of Chronic Diabetes Wound Healing.

The diabetic wound is excessively vulnerable to infection because the diabetic wound suggests delayed and incomplete healing techniques. Presently, wounds and ulcers related to diabetes have additionally increased the medical burden. A diabetic wound can impair mobility, lead to amputations, or even death. In recent times, advanced drug delivery systems have emerged as promising approaches for enhancing the efficacy of wound healing treatments in diabetic patients. This review aims to provide an overview of the current advancements in drug delivery systems in managing chronic diabetic wound healing. This review begins by discussing the pathophysiological features of diabetic wounds, including impaired angiogenesis, elevated reactive oxygen species, and compromised immune response. These factors contribute to delayed wound healing and increased susceptibility to infection. The importance of early intervention and effective wound management strategies is emphasized. Various types of advanced drug delivery systems are then explored, including nanoparticles, hydrogels, transferosomes, liposomes, niosomes, dendrimers, and nanosuspension with incorporated bioactive agents and biological macromolecules are also utilized for chronic diabetes wound management. These systems offer advantages such as sustained release of therapeutic agents, improved targeting and penetration, and enhanced wound closure. Additionally, the review highlights the potential of novel approaches such as antibiotics, minerals, vitamins, growth factors gene therapy, and stem cell-based therapy in diabetic wound healing. The outcome of advanced drug delivery systems holds immense potential in managing chronic diabetic wound healing. They offer innovative approaches for delivering therapeutic agents, improving wound closure, and addressing the specific pathophysiological characteristics of diabetic wounds.

Optimization of Nasal Liposome Formulation of Venlafaxine Hydrochloride using a Box-Behnken Experimental Design.

Background: Intranasal administration is among the most effective alternatives to deliver drugs directly to the brain and prevent first-pass metabolism. Venlafaxine-loaded liposomes are biocompatible carriers that enhance transport qualities over the nasal mucosa. Objective: This research aimed to develop, formulate, characterize, and observe the prepared formulation. Methods: The formulation was developed using the thin-film hydration technique. The response surface plot interrelationship between three independent variables are lipid, cholesterol and polymer and four dependent variables such as particle size, percentage entrapment efficiency, and percentage drug release were ascertained using the Box-Behnken design. Results: The drug-release chitosan-coated liposomes were reported to have a particle size distribution, entanglement efficiency, and 84%, respectively, of 191 ± 34.71 nm, 94 ± 2.71% and 94 ± 2.71%. According to in vitro investigations, liposomes as a delivery system for the nasal route provided a more sustained drug release than the oral dosing form. Conclusions: The intranasal administration of venlafaxine liposomal vesicles effectively enhanced the absolute bioavailability, retention time, and brain delivery of venlafaxine.

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies.

The pathetic malignant mesothelioma (MM) is a extremely uncommon and confrontational tumor that evolves in the mesothelium layer of the pleural cavities (inner lining- visceral pleura and outer lining- parietal pleura), peritoneum, pericardium, and tunica vaginalis and is highly resistant to standard treatments. In mesothelioma, the predominant pattern of lesions is a loss of genes that limit tumour growth. Despite the worldwide ban on the manufacture and supply of asbestos, the prevalence of mesothelioma continues to increase. Mesothelioma presents and behaves in a variety of ways, making diagnosis challenging. Most treatments available today for MM are ineffective, and the median life expectancy is between 10 and 12 months. However, in recent years, considerable progress has already been made in understanding the genetics and molecular pathophysiology of mesothelioma by addressing hippo signaling pathway. The development and progression of MM are related to many important genetic alterations. This is related to NF2 and/or LATS2 mutations that activate the transcriptional coactivator YAP. The X-rays, CT scans, MRIs, and PET scans are used to diagnose the MM. The MM are treated with surgery, chemotherapy, first-line combination chemotherapy, second-line treatment, radiation therapy, adoptive T-cell treatment, targeted therapy, and cancer vaccines. Recent clinical trials investigating the function of surgery have led to the development of innovative approaches to the treatment of associated pleural effusions as well as the introduction of targeted medications. An interdisciplinary collaborative approach is needed for the effective care of persons who have mesothelioma because of the rising intricacy of mesothelioma treatment. This article highlights the key findings in the molecular pathogenesis of mesothelioma, diagnosis with special emphasis on the management of mesothelioma.

Hesperidin-Loaded Lipid Polymer Hybrid Nanoparticles for Topical Delivery of Bioactive Drugs.

Hesperidin is a bioflavonoid constituent that among many other biological activities shows significant wound healing properties. However, the bioavailability of hesperidin when applied topically is limited due to its low solubility and systemic absorption, so novel dosage forms are needed to improve its therapeutic efficacy. The objectives of this study were to develop hesperidin-loaded lipid-polymer hybrid nanoparticles (HLPHNs) to enhance the delivery of hesperidin to endogenous sites in the wound bed and promote the efficacy of hesperidin. HLPHNs were optimized by response surface methodology (RSM) using the Box-Behnken design. HLPHNs were prepared using an emulsion-solvent evaporation method based on a double emulsion of water-in-oil-in-water (w/o/w) followed by freeze-drying to obtain nanoparticles. The prepared formulations were characterized using various evaluation parameters. In addition, the antioxidant activity of HLPHN 4 was investigated in vitro using the DPPH model. Seventeen different HLPHNs were prepared and the HLPHN4 exhibited the best mean particle size distribution, zeta potential, drug release and entrapment efficiency. The values are 91.43 nm, +23 mV, 79.97% and 92.8%, respectively. Transmission electron microscope showed similar spherical morphology as HLPHN4. Differential scanning calorimetry verified the physical stability of the loaded drug in a hybrid system. In vitro release studies showed uniform release of the drug over 24 h. HLPHN4 showed potent antioxidant activity in vitro in the DPPH model. The results of this study suggest that HLPHNs can achieve sustained release of the drug at the wound site and exhibit potent in vitro antioxidant activity.

Phytochemical screening and determination of phenolics and flavonoids in Dillenia pentagyna using UV-vis and FTIR spectroscopy.

Here, we report an ultrasonic-assisted extraction (UAE) of phytochemicals from bark, leaves, sepals, fruits, and seeds of Dillenia pentagyna (Roxb) using different organic solvents such as chloroform, ethanol, and n-hexane. The preliminary phytochemical screening results showed that the ethanolic extract is enriched with phenolics, flavonoids, tannin, saponin, alkaloid, and terpenoids. The profiling of phytochemicals is carried out employing UV-Vis and Fourier-transform infrared (FTIR) spectroscopy analyses. The higher amount of phenolic compounds obtained in the ethanolic extract of bark and leaves as compared to other parts of the plant. Consequently, a higher amount of total flavonoid compounds unveiled in the bark of targeted species. The ethanolic extract of bark and leaves showed good free radical scavenging activity using DPPH with inhibition percentage of 90.58 ± 1.89% and 76.46 ± 1.58%, respectively, in comparison to standard ascorbic acid at 10 µg/mL. Moreover, the half-maximal inhibitory concentration (IC50) value of bark and leaves are 5.64 and 6.54 µg/mL, respectively, in comparison to standard ascorbic acid. With the best of our knowledge, it is the first report pertaining to characterization and quantification of phenols and flavonoids as well as the investigation of the medicinal property in D. pentagyna.

In vitro and In vivo characterization of quercetin loaded multiphase hydrogel for wound healing application.

The present work aim to prepare and evaluate multiphase hydrogel system incorporated with quercetin loaded liposomes (QLH), for wound healing. The quercetin loaded liposomal hydrogel were prepared by taking 15% carbopol and varying gelatin ratio. The clear and transparent hydrogel was obtained by taking ratio of gelatin to carbapol (6/4) compared to other ratios. The best prepared hydrogel were characterized for surface morphology, water vapor transmission rate (WVTR), swelling ratio, hemocompatibility, stability, in-vitro release and in-vivo studies. The evaluated results of (QLH) for surface morphology, WVTR, swelling ratio, hemocompatibility and in-vitro release were found to be significant compared to other prepared formulations. Consequently, on basis of optimized hydrogel was selected to study wound healing activity in albino rats. The results demonstrated accelerated wound-healing with significant decrease in wound closure time compared to conventional dosage form. The results of in-vitro and in-vivo promises reliable mode of treatment for connective tissue disorder as wound healing.

Preparation and optimization of quercetin-loaded liposomes for wound healing, using response surface methodology.

The basic objective of this study was to prepare quercetin-loaded liposomes by the thin film hydration method. The liposomal formulation was optimized using response surface methodology (RSM). A rotation speed of 75 rpm and a water bath temperature of 46°C were finalized as the best for optimized drug-loaded liposomal formulation. In vitro characterization of the quercetin-loaded liposomal formulation was done through some parameters including the entrapment efficiency (EE), drug release (DR), and mean particle size; the resulting values of 86.5 ± 0.42%, 76.5%, and146 nm were found to be standard characterized values respectively. It is concluded that quercetin-loaded liposomal formulations achieve sustained release of drug in wound areas.