Antimicrobial Activity, Stability and Wound Healing Performances of Chitosan Nanoparticles Loaded Recombinant LL37 Antimicrobial Peptide

Author(s):  
Shohreh Fahimirad ◽  
Ehsanollah Ghaznavi-Rad ◽  
Hamid Abtahi ◽  
Nahid Sarlak
2018 ◽  
Vol 51 (2) ◽  
pp. 647-663 ◽  
Author(s):  
Bobin Mi ◽  
Jing Liu ◽  
Yi Liu ◽  
Liangcong Hu ◽  
Yukun Liu ◽  
...  

Background/Aims: Antimicrobial peptides are effective promoters of wound healing but are susceptible to degradation. In this study, we replaced the GIGDP unit on the N-terminal of the endogenous human antimicrobial peptide hBD-2 with APKAM to produce A-hBD-2 and analyzed the effect on wound healing both in vitro and in vivo. Methods: The effects of A-hBD-2 and hBD-2 on cytotoxicity and proliferation in keratinocytes were assessed by Cell Counting Kit-8 assay. The structural stability and antimicrobial activity of hBD-2 and A-hBD-2 were evaluated against Staphylococcus aureus. RNA and proteins levels were evaluated by real-time PCR and western blotting, respectively. Cell migration was evaluated using a transwell assay. Cell cycle analysis was performed by flow cytometry. Wound healing was assessed in Sprague-Dawley rats. Epidermal thickness was evaluated by hematoxylin and eosin staining. Results: We found that hBD-2 exhibited cytotoxicity at high concentrations and decreased the structural stability in the presence of high sodium chloride concentrations. A-hBD-2 exhibited increased structural stability and antimicrobial activity, and had lower cytotoxicity in keratinocytes. A-hBD-2 increased the migration and proliferation of keratinocytes via phosphorylation of EGFR and STAT3 and suppressed terminal differentiation of keratinocytes. We also found that A-hBD-2 elicited mobilization of intracellular Ca2+ and stimulated keratinocytes to produce pro- and anti-inflammatory cytokines and chemokines via phospholipase C activation. Furthermore, A-hBD-2 promoted wound healing in vivo. Conclusion: Our data suggest that A-hBD-2 may be a promising candidate therapy for wound healing.


2019 ◽  
Author(s):  
Tanay Bhatt ◽  
Mruthyunjaya MS ◽  
Aishwarya Bhosale ◽  
Bhavya Bajantri ◽  
Abrar Rizvi ◽  
...  

Author(s):  
Lan Zhang ◽  
Yang Xue ◽  
Sanjana Gopalakrishnan ◽  
Kai Li ◽  
Yong Han ◽  
...  

2021 ◽  
Vol 9 (6) ◽  
pp. 1249
Author(s):  
Johannes Koehbach ◽  
Jurnorain Gani ◽  
Kai Hilpert ◽  
David J Craik

According to the World Health Organization (WHO) the development of resistance against antibiotics by microbes is one of the most pressing health concerns. The situation will intensify since only a few pharmacological companies are currently developing novel antimicrobial compounds. Discovery and development of novel antimicrobial compounds with new modes of action are urgently needed. Antimicrobial peptides (AMPs) are known to be able to kill multidrug-resistant bacteria and, therefore, of interest to be developed into antimicrobial drugs. Proteolytic stability and toxicities of these peptides are challenges to overcome, and one strategy frequently used to address stability is cyclization. Here we introduced a disulfide-bond to cyclize a potent and nontoxic 9mer peptide and, in addition, as a proof-of-concept study, grafted this peptide into loop 6 of the cyclotide MCoTI-II. This is the first time an antimicrobial peptide has been successfully grafted onto the cyclotide scaffold. The disulfide-cyclized and grafted cyclotide showed moderate activity in broth and strong activity in 1/5 broth against clinically relevant resistant pathogens. The linear peptide showed superior activity in both conditions. The half-life time in 100% human serum was determined, for the linear peptide, to be 13 min, for the simple disulfide-cyclized peptide, 9 min, and, for the grafted cyclotide 7 h 15 min. The addition of 10% human serum led to a loss of antimicrobial activity for the different organisms, ranging from 1 to >8-fold for the cyclotide. For the disulfide-cyclized version and the linear version, activity also dropped to different degrees, 2 to 18-fold, and 1 to 30-fold respectively. Despite the massive difference in stability, the linear peptide still showed superior antimicrobial activity. The cyclotide and the disulfide-cyclized version demonstrated a slower bactericidal effect than the linear version. All three peptides were stable at high and low pH, and had very low hemolytic and cytotoxic activity.


2021 ◽  
Vol 8 (2) ◽  
Author(s):  
Yue Li ◽  
QingQing Leng ◽  
XianLun Pang ◽  
Huan Shi ◽  
YanLin Liu ◽  
...  

Abstract Dermal injury, including trauma, surgical incisions, and burns, remain the most prevalent socio-economical health care issue in the clinic. Nanomedicine represents a reliable administration strategy that can promote the healing of skin lesions, but the lack of effective drug delivery methods can limit its effectiveness. In this study, we developed a novel nano-drug delivery system to treat skin defects through spraying. We prepared curcumin-loaded chitosan nanoparticles modified with epidermal growth factor (EGF) to develop an aqueous EGF-modified spray (EGF@CCN) for the treatment of dermal wounds. In vitro assays showed that the EGF@CCN displayed low cytotoxicity, and that curcumin was continuously and slowly released from the EGF@CCN. In vivo efficacy on wound healing was then evaluated using full-thickness dermal defect models in Wistar rats, showing that the EGF@CCN had significant advantages in promoting wound healing. On day 12 post-operation, skin defects in the rats of the EGF@CCN group were almost completely restored. These effects were related to the activity of curcumin and EGF on skin healing, and the high compatibility of the nano formulation. We therefore conclude that the prepared nano-scaled EGF@CCN spray represents a promising strategy for the treatment of dermal wounds.


2021 ◽  
Vol 12 ◽  
Author(s):  
Miho Takahashi ◽  
Yoshie Umehara ◽  
Hainan Yue ◽  
Juan Valentin Trujillo-Paez ◽  
Ge Peng ◽  
...  

In addition to its antimicrobial activity, the skin-derived antimicrobial peptide human β-defensin-3 (hBD-3) promotes keratinocyte proliferation and migration to initiate the wound healing process; however, its effects on fibroblasts, which are the major cell type responsible for wound healing, remain unclear. We investigated the role of hBD-3 in cell migration, proliferation and production of angiogenic growth factors in human fibroblasts and evaluated the in vivo effect of hBD-3 on promoting wound healing and angiogenesis. Following hBD-3 treatment, the mouse wounds healed faster and showed accumulation of neutrophils and macrophages in the early phase of wound healing and reduction of these phagocytes 4 days later. hBD-3-treated wounds also displayed an increased number of fibroblasts and newly formed vessels compared to those of the control mice. Furthermore, the expression of various angiogenic growth factors was increased in the hBD-3-treated wounds. Additionally, in vitro studies demonstrated that hBD-3 enhanced the secretion of angiogenic growth factors such as fibroblast growth factor, platelet-derived growth factor and vascular endothelial growth factor and induced the migration and proliferation of human fibroblasts. The hBD-3-mediated activation of fibroblasts involves the fibroblast growth factor receptor 1 (FGFR1)/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathways, as evidenced by the inhibitory effects of pathway-specific inhibitors. We indeed confirmed that hBD-3 enhanced the phosphorylation of FGFR1, JAK2 and STAT3. Collectively, the current study provides novel evidence that hBD-3 might be a potential candidate for the treatment of wounds through its ability to promote wound healing, angiogenesis and fibroblast activation.


2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Sedighe Sadat Hashemi kamangar ◽  
Houtan Zareian ◽  
Abbas Bahador ◽  
Maryam Pourhajibagher ◽  
Zahra Bashareh ◽  
...  

Objectives. The present study evaluated the antimicrobial effects of fissure sealants containing chitosan nanoparticles. Materials and Methods. Antibacterial effect of Master Dent fissure sealant alone and after incorporating chitosan nanoparticles was evaluated on Streptococcus mutans, sanguis, and Lactobacillus acidophilus. Biofilm growth was evaluated by determining colony counts. Antimicrobial effect was determined on days 3, 15, and 30 by counting microbial colonies using eluted components test. One-way ANOVA, Tukey HSD tests, t test, and two-way ANOVA were used for statistical analyses (α = 0.05). Results. Biofilm inhibition test showed that fissure sealant containing 1 wt.% chitosan decreased colony counts significantly ( P < 0.05 ). Eluted components test with S. mutans and sanguis showed significant decrease in colony counts during the first 15 days in chitosan containing group; however, from day 30, antimicrobial activity decreased noticeably, with no significant difference from control group ( P > 0.05 ). Antimicrobial activity against L. acidophilus was maintained in chitosan group up to 30 days, and decrease in colony counts was significant ( P < 0.05 ). Conclusion. According to the results of this study, incorporation of 1 wt.% chitosan into fissure sealant induced an antimicrobial activity. Antibacterial effect on L. acidophilus persisted for longer time (30 days) compared to the two other bacterial species (15 days).


Sign in / Sign up

Export Citation Format

Share Document