Multifunctional Delivery Nanosystems Formed by Degradable Antibacterial Poly(Aspartic Acid) Derivatives for Infected Skin Defect Therapy

Abstract

Nucleic acid (NA)‐based therapy is promising for tissue repair, such as skin and bone defect therapy. However, bacterial infections often occur in the process of tissue healing. The ideal treatment of tissue repair requires both anti‐infection and simultaneous tissue healing. The epidermal growth factor (EGF) plays an important role in wound healing processes. In this work, degradable antibacterial gene vectors based on tobramycin (clinically relevant antibiotic) conjugated poly(aspartic acid) (TPT) are proposed as multifunctional delivery nanosystems of plasmid encoding EGF (pEGF) to realize the antibacterial therapy and tissue healing of infected skin defects. TPT has low cytotoxicity and good degradability, which is helpful in the NA delivery process. TPT demonstrates good transfection performances and hemocompatibility, as well as excellent antibacterial activities in vitro. The outstanding pEGF delivery ability of TPT and the bioactivity of expressed EGF facilitate the proliferation of fibroblast cells. The effective in vivo infected skin defect therapy is also demonstrated with TPT/pEGF nanocomplexes, where skin tissue healing is promoted. The present work opens new avenues for the design of multifunctional delivery nanosystems with antibacterial ability to treat infected tissue defect.

Polymer-based non-viral vectors for gene therapy in the skin

“…Song et al reported a polyplex of a plasmid encoding EGF with PASA, formed by ROP of NCA with the antibiotic tobramycin employed as an initiator and subsequent constituent. 123 Evaluation of this polyplex in a rat in vivo skin wound healing model demonstrated an adequate degradation profile, low cytotoxicity, hemocompatibility, antibacterial activity, and the robust ability to transfect fibroblasts and increase proliferation.…”

Controllable Disulfide Exchange Polymerization of Polyguanidine for Effective Biomedical Applications by Thiol‐Mediated Uptake

“…The combined plasmid pKR-p53, which can simultaneously express photosensitive protein (KillerRed) and apoptosis-related protein (P53) in the same cell to achieve the combined therapy of p53-mediated gene/PDT therapy [22] was used to verify the gene delivery ability of The epidermal growth factor (EGF) can effectively promote tissue healing by stimulating the proliferation and migration of keratinocytes, endothelial cells, and fibroblasts. [23] pEGF delivered by an excellent gene vector can overcome the reduction of EGF in wounds, [24] and was chosen to further confirm the gene delivery ability of…”

Biodegradable Antibacterial Polymeric Nanosystems: A New Hope to Cope with Multidrug‐Resistant Bacteria

“…More recently, multifunctional delivery nanosystems containing conjugated tobramycin was developed to eradicate bacterial infections for wound tissue recovery . The tobramycin‐conjugated nanosystems were synthesized by ring‐opening reaction of β‐benzyl‐l‐aspartate N‐carboxy anhydride (BLA‐NCA) starting from the amino groups of tobramycin.…”

“…b) Photographs of wound healing processes of rat model. Reproduced with permission . Copyright 2018, Wiley‐VCH.…”