The insect nervous system is critical for its functional integrity. The cholinergic system, of which acetylcholinesterase (AChE) is a key enzyme, is essential to the Anopheles (consisting of major malaria vector species) nervous system. Furthermore, the nervous system is also the primary target site for insecticides used in malaria vector control programs. Insecticides, incorporated in insecticide-treated nets and used for indoor residual spraying, are a core intervention employed in malaria vector control. However, Anopheles resistance against these insecticides has grown rapidly. Due to this major setback, novel agents with potential activity against resistant Anopheles and/or capacity to overcome resistance against current WHO-approved insecticides are urgently needed. The essential oils have the potential to be natural sources of novel insecticides with potential to inhibit the Anopheles AChE target. In the current review, the scientific evidence highlights the ability of essential oils and specific essential oil constituents to serve as anticholinesterase insecticides. For this reason, the published data from scientific databases on the essential oils and essential oil constituents on anticholinesterase, ovicidal, larvicidal, pupicidal and adulticidal activities were analyzed. The identification of major constituents in active essential oils and their possible influence on the biological activity have also been critically evaluated. Furthermore, the toxicity to mammals as well as potential activity against the mammalian AChE target has also been reviewed. The importance of identifying novel potent insecticides from essential oils has been discussed, in relation to human safety and cost-effectiveness. Finally, the critical insights from this review can be used to inform future researchers towards potent and safe anticholinesterase insecticides for the management of Anopheles malaria vectors.

As one of the most cutting-edge and promising polymer crosslinked network nanoparticle systems. Polymer nano-sized hydrogels (nanogels) have been a hot topic in the biomedical field over the last few decades. Due to their unique characteristics, which include their relatively high drug encapsulation efficiency, ease of preparation, high tunability, low toxicity, high stability in serum and responsive behavior to a range of stimuli to facilitate drug release. Nanogels are thought to be the next generation of drug delivery systems that can completely change the way that drug delivery systems have an impact on patients’ lives. Nanogels have demonstrated significant potential in a variety of fields, including chemotherapy, diagnosis, organ targeting, and delivery of bioactive molecules of different dimensions. However, the lack of substantial clinical data from nanogels becomes one of the major barriers to translating the nanogel concept into a practical therapeutic application for many disease conditions. In addition, nanogel safety profiles have been the major concern that hinders it advancement to the clinical trial phase. This review aims to emphasize the unique properties of nanogels as delivery systems for a variety of bioactive molecules over other nano-delivery systems. Also, this review attempts to give insight into the recent progress in nanogels as a carrier in the field of nanomedicine to overcome complex biological barriers. Relevant scientific data and clinical rationale for the development and the potential use of nanogel as a carrier for targeted therapeutic interventions are discussed. Finally, the concluding points of this review highlight the importance of understanding the long-term toxicity profile of nanogel within the biological system to fully understand their biocompatibility.

Psoriasis vulgaris (PV) is a common chronic disease, affecting much of the population. Hydrocortisone (HCT) is currently utilized as a PV treatment; however, it is associated with undesirable side effects. The aim of this research was to create a thermo-responsive nano-hydrogel delivery system. HCT-loaded sorbitan monostearate (SMS)-polycaprolactone (PCL) nanoparticles, encapsulated with thermo-responsive hydrogel carboxymethyl cellulose (CMC), were synthesized by applying the interfacial polymer-deposition method following solvent displacement. The nanoparticles’ properties were evaluated employing Differential Scanning Colorimetry, Thermogravimetric Analysis, Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy, Zeta sizer, Ultraviolet/Visual spectroscopy, and cytotoxicity testing. The nanoparticle sizes were 110.5 nm, with polydispersity index of 0.15 and zeta potential of −58.7 mV. A drug-entrapment efficacy of 76% was attained by the HCT-loaded SMS-PCL nanoparticles and in vitro drug-release profiles showed continuous drug release over a period of 24 hrs. Keratinocyte skin cells were treated with HCT-loaded SMS-PCL nanoparticles encapsulated with CMC; the results indicated that the synthesized drug-delivery system was less toxic to the keratinocyte cells compared to HCT. The combined trials and results from the formulation of HCT-loaded SMS-PCL nanoparticles encapsulated with CMC showed evidence that this hydrogel can be utilized as a potentially invaluable formulation for transdermal drug delivery of HCT, with improved efficacy and patient conformity.

Background/Objectives: Helicobacter pylori infects approximately half of the global population, causing chronic gastritis, peptic ulcers, and gastric cancer, a leading cause of cancer mortality. While current therapies face challenges from rising antibiotic resistance, particularly to clarithromycin, alongside treatment complexity and costs, the World Health Organization has prioritized the development of new antibiotics to combat this high-risk pathogen. In this study, we employed computer-aided drug design (CADD) methodologies, including molecular docking, Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) analysis, molecular dynamics (MD) simulations, and Density Functional Theory (DFT) calculations, to explore the potential repurposing of FDA-approved agents as inhibitors of Helicobacter pylori shikimate kinase (HpSK). Methods: Using the Glide module, the HTVS method was initially applied to screen 1615 FDA-approved agents followed by extra-precision (XP) docking for the obtained 111 hits. The obtained XP scores were used to confine the results to those hits with a score above the reference ligand, shikimate, score. This yielded 31 final hits with an XP score above −5.867. MM-GBSA calculations were performed on these top candidates and the reference ligand to refine the analysis and compounds’ prioritization. Results: The 31 compounds displayed binding free energy (ΔG_bind) values ranging from 3.61 to −55.92 kcal/mol, with shikimate exhibiting a ΔG_bind of −34.24 kcal/mol and 10 hits having a lower ΔG_bind value. Out of these ten, three drugs—Dolutegravir, Cangrelor, and Isavuconazonium—were selected for further analysis based on their drug-like properties. Robust and stable binding profiles for both Isavuconazonium and Cangrelor were verified via molecular dynamics simulation. Additionally, Density Functional Theory (DFT) analysis was conducted, and the Highest Occupied Molecular Orbitals (HOMOs), Lowest Unoccupied Molecular Orbitals (LUMOs), and the energy gap (HLG) between them were calculated. All three drug candidates displayed lower HLG values than shikimate, suggesting higher reactivity and more efficient electronic transitions than the reference ligand. Conclusions: These findings suggest that the identified drugs, although not optimal for direct repurposing, would serve as promising leads against Helicobacter pylori shikimate kinase. These drugs could be valuable leads for experimental assessment and further optimization, particularly with no prototype yet identified. In terms of potential for clinical repurposing, the results point to diflunisal as a promising candidate for further testing.

High-dose methotrexate (HDMTX) is one of the chemotherapeutic agents used to treat a variety of cancers in both adults and children. However, the toxicity associated with HDMTX has resulted in the spread of infections and treatment interruption. Further, poor bioavailability due to efflux pump activities mediated by P-glycoprotein has also been linked to poor therapeutic effects of methotrexate following oral administrations. D-α-Tocopheryl poly-ethylene glycol 1000 succinate (TPGS) is known to improve the bioavailability of poorly soluble drugs by inhibiting P-gp efflux activities, thus enhancing cellular uptake. Therefore, to achieve improved bioavailability for MTX, this study aimed to design and develop a novel drug delivery system employing TPGS and a biodegradable polymer, i.e., PLGA, to construct methotrexate-loaded nanoparticles fixated in alginate-gelatine 3D printable hydrogel ink to form a solid 3D printed tablet for oral delivery. The results indicated that high accuracy (>95%) of the 3D printed tablets was achieved using a 25 G needle. In vitro, drug release profiles were investigated at pH 1.2 and pH 7.4 to simulate the gastrointestinal environment. The in vitro release profile displayed a controlled and prolonged release of methotrexate over 24 h. The in silico modeling study displayed P-gp ATPase inhibition, suggesting enhanced MTX absorption from the gastrointestinal site. The 3D-printed hydrogel-based tablet has the potential to overcome the chemotherapeutic challenges that are experienced with conventional therapies.