Abstract
The present work is focused on the design and development of novel amphotericin B (AmB)-conjugated biocompatible and biodegradable polypeptide hydrogels to improve the antifungal activity. Using three kinds of promoting self-assembly groups (2-naphthalene acetic acid (Nap), naproxen (Npx) and dexamethasone (Dex)) and polypeptide sequence (Phe-Phe-Asp-Lys-Tyr, FFDKY), we successfully synthesized the Nap-FFDK(AmB)Y gels, Npx-FFDK(AmB)Y gels and Dex-FFDK(AmB)Y gels. The AmB-conjugated hydrogelators are highly soluble in different aqueous solutions. The cryo-transmission electron microscopy and scanning electron microscopy micrographs of hydrogels afford nanofibres with a width of 20–50 nm. Powder X-ray diffraction analyses demonstrate that the crystalline structures of the AmB and Dex are changed into amorphous structures after the formation of hydrogels. Circular dichroism spectra of the solution of blank carriers and the corresponding drug deliveries further help elucidate the molecular arrangement in gel phase, indicating the existence of turn features. The in vitro drug releases suggest that the AmB-conjugated hydrogels are suitable as drug-controlled release vehicles for hydrophobic drugs. The antifungal effect of AmB-conjugated hydrogels significantly exhibits the antifungal activity against Candida albicans. The results of the present study indicated that the AmB-conjugated hydrogels are suitable carriers for poorly water soluble drugs and for enhancement of therapeutic efficacy of antifungal drugs.
Highlights
Invasive fungal infection has a significant influence on animal and plant life, which is a major cause of mortality that kills approximately 1.5 million people every year [1]
naphthalene acetic acid (Nap)-Amphotericin B (AmB), Npx-AmB and Dex-AmB hydrogelators are highly soluble in different aqueous solutions, such as water, PBS solutions and culture solutions
It is noted that Nap-AmB and Npx-AmB hydrogels randomly assemble in dendritic clusters, while Dex-AmB hydrogels are observed as aquatic plants or feather structures
Summary
Invasive fungal infection has a significant influence on animal and plant life, which is a major cause of mortality that kills approximately 1.5 million people every year [1]. The principles of the design are described as follows: (i) the peptide sequence of hydrogels contains Asp-Lys (DK) dipeptide fragments because it is crucial for antibacterial activity [12]—we hope that it can assist AmB to enhance antifungal activity; (ii) dipeptide of phenylalanine (FF) has been widely used to construct molecular hydrogelators; (iii) 2-naphthalene acetic acid (Nap) and naproxen (Npx) are frequently used to promote self-assembly—in the previous literature, Npx-FF fragments exhibit anti-inflammatory effect [13]; and (iv) dexamethasone (Dex) is an anti-inflammatory which is usually given alone or in combination with other antifungal drugs. Dex could reduce allergic reactions and the cell damage caused by AmB [14] These are owing to the immunosuppressive effects and the varying permeability of cell membranes of Dex [15]. Chemical, physical and antifungal properties of AmB-conjugated hydrogels are examined
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