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The present study aimed to fabricate and evaluate the therapeutic efficacy of pH-responsive Ibuprofen (IB) nanoparticles (NPs) loaded transdermal hydrogel against rheumatoid arthritis (RA). The IB loaded Eudragit® L 100 (EL 100) nanoparticles were formulated through a modified nanoprecipitation technique and optimized using central composite design software. The optimized NPs were loaded into Carbopol® 934-based hydrogel by solvent evaporation method and were analyzed for physicochemical characteristics. The mean particle size of the prepared NPs was 48 nm with an entrapment efficiency of 90%. The transdermal hydrogel showed a pH-responsive sustained drug release and high penetration through the skin. Moreover, the prepared nanocarrier system exhibited therapeutic efficacy at inflamed joints' sites both in acute and chronic RA mice model. The therapeutic efficacy of the prepared formulation was confirmed through the results of various behavioral, biochemical, and cytokines-based assays. Similarly, the assessment of histopathological and radiological images, as well as the skin irritation studies further strengthens the potential use of the prepared formulation through the transdermal route. The current findings suggested that IB loaded pH-responsive NPs based transdermal hydrogel can be used as an efficient agent to manage RA., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polysaccharides, due to their outstanding properties, have attracted the attention of researchers, working in the biomedical field and especially of those working in drug delivery. Modified/functionalized polysaccharides further increase the importance for various applications. Delivery of therapeutics for diverse ailments in different endocrine glands and hormones safely, is a focal point of researchers working in the field. Among the routes followed, the transdermal route is preferred due to non-exposure of active moieties to the harsh gastric environment and first-pass metabolism. This review starts with the overview of polysaccharides used for the delivery of various therapeutic agents. Advantages of polysaccharides used in the transdermal route are addressed in detail. Types of polysaccharides will be elaborated through examples, and in this context, special emphasis will be on the polysaccharides being used for synthesis of the membranes/films. Techniques employed for their modification to design novel carriers for therapeutics delivery will also be discussed. The review will end with a brief discussion on recent developments and future perspectives for delivery of therapeutic agents, and vaccine development., (© 2021 Wiley-VCH GmbH.)

The measurement of biological processes at a molecular and cellular level serves as a basis for molecular imaging. As compared with traditional imaging approaches, molecular imaging functions to probe molecular anomalies that are the basis of a disease rather than the evaluation of end results of these molecular changes. Proteases play central role in tumor invasion, angiogenesis and metastasis thus can be exploited as a target for imaging probes in early diagnosis and treatment of tumors. Molecular imaging of protease has undergone tremendous breakthroughs in the field of diagnosis. It allows the clinicians not only to see the tumor location but also provides an insight into the expression and activity of different types of markers associated with the tumor microenvironment. These imaging techniques are expected to have a huge impact on early cancer detection and personalized cancer treatment. Effective development of protease imaging probes with the highest in vivo biocompatibility, stability and most appropriate pharmacokinetics for clinical translation will upsurge the success level of early cancer detection and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin ( p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC 0- t , and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

Nanotechnology has burgeoned over last decade exploring varieties of novel applications in all areas of science and technology. Utilisation of bio-friendly polymers for engineering nanostructures (NS) improves safety and efficacy in drug delivery. Biopolymers not merely employed for fabricating drug carriers but also leveraged for surface functionalisation of other NS to impart bio-mimicking properties. Biopolymer functionalised NS garnered researcher's attention because of their potential to enhance skin permeability of drug cargo. Biopolymers, i.e. cell-penetrating peptides (CPP), chitosan and hyaluronic acid not only enhance skin permeability but also add multiple functions due to their intrinsic biomimetic properties. This multifunctional drug delivery system is a promising tool to achieve skin delivery of large number of therapeutic agents. In this review, functionalisation of NS with biopolymers particularly polysaccharides and polypeptides is discussed in detail. In particular, applications of these functionalised NS for TDDS is elaborated. Moreover, this review provides framework for elaborating importance of functionalisation of NS to enhance skin permeability and depicts advantages of biopolymers to construct more biocompatible carriers for drug cargos.

Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocytes can be used as a carrier for delivery of active agents into tissues, where other carriers have no significant access. Targeting monocytes is possible both through passive and active targeting, the former one is simply achieved by enhanced permeation and retention effect while the later one by attachment of ligands on the surface of the lipid-based particulate system. Monocytes have many receptors e.g., mannose, scavenger, integrins, cluster of differentiation 14 (CD14) and cluster of differentiation 36 (CD36). The ligands used against these receptors are peptides, lectins, antibodies, glycolipids, and glycoproteins. This review encloses extensive introduction of monocytes as a suitable carrier system for drug delivery, the design of lipid-based carrier system, possible ways for delivery of therapeutics to monocytes, and the role of monocytes in the treatment of life compromising diseases such as cancer, inflammation, stroke, etc., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Metallo-elements including Vanadium (V) have strong affinity for sulfhydryl (-SH) groups in biological molecules including Glutathione (GSH) in tissues. Because of this fact it was of interest to further investigate the interaction of Ammonium Vanadate [NH(4)VO(3)] with Glutathione as a biomarker of toxicity and the role of Glutathione in the detoxification and conjugation pr(o)Cesses in whole blood components including plasma and cytosolic fraction. Effects of different concentrations of Ammonium Vanadate [NH(4)VO(3)] on the level of reduced Glutathione in whole blood components (Plasma and Cytosolic fraction) were examined. GSH depletion in plasma and cytosolic fraction was Ammonium Vanadate's concentration-dependent. Depleted GSH level was more pronounced with more incubation time period. These findings show that changes in the GSH status produced by Ammonium Vanadate could be due to either by adduct formation of Vanadium and glutathione i.e. (V-SG) or by increased production of oxidized Glutathione (2GSH +V(+5) → GSSG). This change in GSH metabolic status provides some information regarding the mechanism of toxicity by Ammonium Vanadate and the protective role of glutathione.

Silver nitrate (AgNO3) effect on the status of reduced glutathione (GSH), the major non-protein thiol in blood components were examined using freshly isolated plasma and cytosolic fraction of whole blood of healthy human volunteer. AgNO3 had significant effects on GSH contents reduction in plasma and cytosolic fraction of blood. Effect or reduction in GSH content was more pronounced or significant at AgNO3 concentration with time intervals (minutes to hours). Depletion of GSH in plasma and cytosolic fraction of blood by the addition of AgNO3 indicates that AgNO3 penetrated the cell membrane and reacted with GSH, depleted its contents mostly due to oxidation of reduced Glutathione (GSH) to glutathione disulphide (GSSG) 2 GSH-GSSG+2H+ or likely that AgNO3 after penetration formed a Silver-Glutathione (Ag-SG) complex. Time dependent effect of AgNO3 on the chemical status of glutathione was discussed in vitro in this paper which in principle presents the model of in vivo reaction, which will be the precise indirect impression of AgNO3 detoxification resulting by the interaction with GSH.