Abstract
The self-assembly of hydrophobically modified polymers has become a research hotspot due to its wide application in the biomedical field. Recombinant human epidermal growth factors (rhEGFs) are molecules that are able to enhance wound healing; however, they have a short half-life and require sustained action to enhance their mitogenic effect on epithelial cells. Here, we proposed a new delivery system to avoid the inhibition of rhEGF by various enzymes, thus improving its bioavailability and sustained release. The amphiphilic polymer was composed of conjugated linoleic acid (CLA) and carboxymethyl chitosan (CMCS), which were further characterized by fourier transformed infrared spectroscopy (FTIR) and 1H nuclear magnetic resonance (1H NMR). Then, the self-assembly behavior of CLA–CMCS (CC) polymer in water was observed in which the particle size of CC decreased from 196 to 155 nm with the degree of CLA substitution increasing. The nanoparticles were loaded with rhEGF and the maximum rhEGF loading efficiency (LE) of CC3 nanoparticles was 82.43 ± 3.14%. Furthermore, CC nanoparticles (NPs) exhibited no cytotoxicity for L929 cells, and cell proliferation activity was well preserved after rhEGF loading to CC-NPs and was comparable to that of free rhEGF. Topically applied rhEGF:CC-NPs significantly accelerated the wound-closure rate in full thickness, which was most probably due to its sustained release and enhanced skin permeation. In conclusion, carboxymethyl chitosan-based nanoparticles were constructed and showed good cytocompatibility. Moreover, these findings also demonstrated the therapeutic potential of rhEGF:CC-NPs as a topical wound-healing drug carrier.
Highlights
Skin wound healing is a complex and long process involving coagulation, inflammation, and the formation of new skin tissue [1]
10 hours was observed, which was probably due to the full dissolution of the carboxymethyl chitosan (CMCS) outer layer in condition according to its polyampholytic character nature, and the internal embedded Recombinant human epidermal growth factors (rhEGFs) is the designated condition according to its polyampholytic character nature, and the internal gradually released
CC-NPs prepared in this way were uniform and stable cross-linking with carboxymethyl chitosan
Summary
Skin wound healing is a complex and long process involving coagulation, inflammation, and the formation of new skin tissue [1]. Self-assembled nanoparticles based on poly(lactic–co–glycolic acid) (PLGA) and polysaccharides, which are composed of an inner hydrophobic core and outer hydrophilic shell, have been widely reported to improve drug delivery efficiency [14,15,16] These nanoparticles are suitable delivery systems for skin wound treatment due to their high drug concentration in the treatment area and the ability to induce tissue repair. Their nano size ensures that the particles are in close contact with the skin, while controlling the release of the drug to increase the action time of the drug on the skin surface [17]. The rhEGF-loaded CC-NPs were applied to the full thickness excised wound model of mice, and the wound healing was evaluated according to wound closure, inflammatory recovery, and epithelial regeneration
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