Leishmaniasis, caused by the intramacrophage protozoan parasite Leishmania donovani, is a life-threatening yet neglected vector-borne disease. Few medications for the treatment of this disease are available. However, targeted delivery of drugs to macrophages remains a significant concern. Macrophages are equipped with many receptors, and therefore putting suitable ligands in the macrophage targeting drug delivery vehicle gained a lot of attention. One such receptor is the mannose receptor, abundantly expressed by macrophages. To treat this deadly disease, in this study, a mannose containing composite hydrogel is prepared by combining a self-aggregating short peptide (Nap-FFGE-NH 2 , Pep-A) and a mannose containing non-aggregating peptide (Nap-FF-mannosyl, Pep-B). The self-aggregation of the composite hydrogel is evaluated using various spectroscopic and microscopic techniques. Intermolecular hydrogen bonding and π-π stacking lead to an antiparallel β-sheet like arrangement of the peptides. Notably, the composite hydrogel showed shear-thinning and syneresis properties. Moreover, the composite hydrogel was found to be stable in cell-culture media, biodegradable and non-toxic to the macrophages. Both control and infected macrophages showed effective cell growth and proliferation when subjected to the composite 2D and 3D hydrogel matrix. When treated with Amphotericin B loaded composite hydrogel, the drug was effectively delivered to kill the parasite in the infected macrophages. Almost 3.5 fold decrease in the parasite burden was recorded when infected cells were treated with drug-loaded composite hydrogel. The injectability, biodegradability, non-cytotoxicity, and efficient drug delivery properties of the mannosefunctionalized hydrogel make it a suitable candidate for the treatment of Leishmaniasis.
An intricate synergism between multiple biochemical processes and physical conditions determines the formation and function of various biological self‐assemblies. Thus, a complex set of variables dictate the far‐from‐equilibrium nature of these biological assemblies. Mimicking such systems synthetically is a challenging task. We report multi‐stimuli responsive transient coacervation of an aldehyde‐appended polymer and a short peptide. The coacervates are formed by the disulphide linkages between the peptide molecules and the imine bond between the polymer and the peptide. Imines are susceptible to pH changes and the disulphide bonds can be tuned by oxidation/reduction processes. Thus, the coacervation is operational only under the combined effect of appropriate pH and oxidative conditions. Taking advantage of these facts, the coacervates are transiently formed under a pH cycle (urea‐urease/gluconolactone) and a non‐equilibrium redox cycle (TCEP/H2O2). Importantly, the system showed high adaptability toward environmental changes. The transient existence of the coacervates can be generated without any apparent change in size and shape within the same system through the sequential application of the above‐mentioned nonequilibrium reaction cycles. Additionally, the coacervation allows for efficient encapsulation/stabilisation of proteins. Thus, the system has the potential to be used for protein/drug delivery purposes in the future.
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