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.

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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.

Single dose high-throughput screening (HTS) followed by dose-response evaluations is a common strategy for the identification of initial hits for further development. Early identification and exclusion of false positives is a cost-saving and essential step in early drug discovery. One of the mechanisms of false positive compounds is the formation of aggregates in assays. This study evaluates the mechanism(s) of inhibition of a set of 14 compounds identified previously as actives in Mycobacterium tuberculosis (Mt) cell culture screening and in vitro actives in Mt shikimate kinase (MtSK) assay. Aggregation of hit compounds was characterized using multiple experimental methods, LC-MS, HNMR, dynamic light scattering (DLS), transmission electron microscopy (TEM), and visual inspection after centrifugation for orthogonal confirmation. Our results suggest that the investigated compounds containing oxadiazole-amide and aminobenzothiazole moieties are false positive hits and non-specific inhibitors of MtSK through aggregate formation.

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.

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A micro-in-macro gastroretentive and gastrofloatable drug delivery system (MGDDS), loaded with the model-drug ciprofloxacin, was developed in this study to address the limitations commonly experienced in narrow-absorption window (NAW) drug delivery. The MGDDS, which consists of microparticles loaded in a gastrofloatable macroparticle (gastrosphere) was designed to modify the release of ciprofloxacin, allowing for an increased drug absorption via the gastrointestinal tract. The prepared inner microparticles (1–4 µm) were formed by crosslinking chitosan (CHT) and Eudragit® RL 30D (EUD), with the outer gastrospheres prepared from alginate (ALG), pectin (PEC), poly(acrylic acid) (PAA) and poly(lactic-co-glycolic) acid (PLGA). An experimental design was utilized to optimize the prepared microparticles prior to Fourier Transition Infrared (FTIR) spectroscopy, Scanning Electron Microscopy (SEM) and in vitro drug release studies. Additionally, the in vivo analysis of the MGDDS, employing a Large White Pig model and molecular modeling of the ciprofloxacin-polymer interactions, were performed. The FTIR results determined that the crosslinking of the respective polymers in the microparticle and gastrosphere was achieved, with the SEM analysis detailing the size of the microparticles formed and the porous nature of the MGDDS, which is essential for drug release. The in vivo drug release analysis results further displayed a more controlled ciprofloxacin release profile over 24 h and a greater bioavailability for the MGDDS when compared to the marketed immediate-release ciprofloxacin product. Overall, the developed system successfully delivered ciprofloxacin in a control-release manner and enhanced its absorption, thereby displaying the potential of the system to be used in the delivery of other NAW drugs.