BackgroundImpaired wound healing is the most common and significant complication of Diabetes. While most other complications of Diabetes have better treatment options, diabetic wounds remain a burden as they can cause pain and suffering in patients. Wound closure and repair are orchestrated by a sequence of events aided by the release of pro-inflammatory cytokines, which are dysregulated in cases of Diabetes, making the wound environment unfavorable for healing and delaying the wound healing processes. This concise review provides an overview of the dysregulation of pro-inflammatory cytokines and offers insights into better therapeutic outcomes.Purpose of reviewAlthough many therapeutic approaches have been lined up nowadays to treat Diabetes, there are no proper treatment modalities proposed yet in treating diabetic wounds due to the lack of understanding about the role of inflammatory mediators, especially Pro-inflammatory mediators- Cytokines, in the process of Wound healing which we mainly focus on this review.Recent findingsAlthough complications of Diabetes mellitus are most reported after years of diagnosis, the most severe critical complication is impaired Wound Healing among Diabetes patients. Even though Trauma, Peripheral Artery Disease, and Peripheral Neuropathy are the leading triggering factors for the development of ulcerations, the most significant issue contributing to the development of complicated cutaneous wounds is wound healing impairment. It may even end up with amputation. Newer therapeutic approaches such as incorporating the additives in the present dressing materials, which include antimicrobial molecules and immunomodulatory cytokines is of better therapeutic value.SummaryThe adoption of these technologies and the establishment of novel therapeutic interventions is difficult since there is a gap in terms of a complete understanding of the pathophysiological mechanisms at the cellular and molecular level and the lack of data in terms of the assessment of safety and bioavailability differences in the individuals’ patients. The target-specific pro-inflammatory cytokines-based therapies, either by upregulation or downregulation of them, will be helpful in the wound healing process and thereby enhances the Quality of life in patients, which is the goal of drug therapy.
Nanogels are highly recognized as adaptable drug delivery systems that significantly contribute to improving various therapies and diagnostic examinations for different human diseases. These three-dimensional, hydrophilic cross-linked polymers have the ability to absorb large amounts of water or biological fluids. Due to the growing demand for enhancing current therapies, nanogels have emerged as the next-generation drug delivery system. They effectively address the limitations of conventional drug therapy, such as poor stability, large particle size, and low drug loading efficiency. Nanogels find extensive use in the controlled delivery of therapeutic agents, reducing adverse drug effects and enabling lower therapeutic doses while maintaining enhanced efficacy and patient compliance. They are considered an innovative drug delivery system that highlights the shortcomings of traditional methods. This article covers several topics, including the involvement of nanogels in the nanomedicine sector, their advantages and limitations, ideal properties like biocompatibility, biodegradability, drug loading capacity, particle size, permeability, non-immunological response, and colloidal stability. Additionally, it provides information on nanogel classification, synthesis, drug release mechanisms, and various biological applications. The article also discusses barriers associated with brain targeting and the progress of nanogels as nanocarriers for delivering therapeutic agents to the central nervous system.
In our study, a structure-based virtual screening study was conducted to identify potent ITK inhibitors, as ITK is considered to play an important role in the treatment of inflammatory diseases. We developed a structure-based pharmacophore model using the crystal structure (PDB ID: 3MJ2) of ITK complexed with BMS-50944. The most predictive model, SB-Hypo1, consisted of six features: three hydrogen-bond acceptors (HBA), one hydrogen-bond donor (HBD), one ring aromatic (RA), and one hydrophobic (HY). The statistical significance of SB-Hypo1 was validated using wide range of test set molecules and a decoy set. The resulting well-validated model could then be confidently used as a 3D query to screen for drug-like molecules in a database, in order to retrieve new chemical scaffolds that may be potent ITK inhibitors. The hits retrieved from this search were filtered based on the maximum fit value, drug-likeness, and ADMET properties, and the hits that were retained were used in a molecular docking study to find the binding mode and molecular interactions with crucial residues at the active site of the protein. These hits were then fed into a molecular dynamics simulation to study the flexibility of the activation loop of ITK upon ligand binding. This combination of methodologies is a valuable tool for identifying structurally diverse molecules with desired biological activities, and for designing new classes of selective ITK inhibitors.
: Conventional delivery of antidiabetic drugs faces many problems like poor absorption, low bioavailability, and drug degradation. Nanoemulsion is a unique drug technology which is very suitable for the delivery of antidiabetic drugs. In recent years the flaws of delivering anti-hypoglycaemic drugs have been overcome by choosing nanoemulsion drug technology. They are thermodynamically stable and also deliver the therapeutic agent for a longer duration. Generally, Nanoemulsions are made up of either oil-in-water or water-in-oil and size of the droplets is from fifty to thousand nanometer. Surfactants are critical substances which are added in the manufacturing of nanoemulsions. Only the surfactants which are approved for human use can be utilized in the manufacturing of nanoemulsions. Generally, the preparation of emulsions includes mixing of the aqueous phase and organic phase and using surfactant with proper agitation. Nanoemulsions are used for antimicrobial drugs, and they are also used in the prophylaxis of cancer, diabetics. Reduction in the droplet size may cause variation in the elastic and optical behaviour of nanoemulsions.
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