Controlled Delivery of Vancomycin from Collagen-tethered Peptide Vehicles for the Treatment of Wound Infections

Abstract

Despite the great promise of antibiotic therapy in wound infections, antibiotic resistance stemming from frequent dosing diminishes drug efficacy and contributes to recurrent infection. To identify improvements in antibiotic therapies, new antibiotic delivery systems that maximize pharmacological activity and minimize side effects are needed. In this study, we developed elastin-like peptide and collagen-like peptide nanovesicles (ECnVs) tethered to collagencontaining matrices to control vancomycin delivery and provide extended antibacterial effects against methicillin-resistant Staphylococcus aureus (MRSA). We observed that ECnVs showed enhanced entrapment efficacy of vancomycin by 3-fold as compared to liposome formulations. Additionally, ECnVs enabled the controlled release of vancomycin at a constant rate with zero-order kinetics, whereas liposomes exhibited first-order release kinetics. Moreover, ECnVs could be retained on both collagen-fibrin (co-gel) matrices and collagen-only matrices, with differential retention on the two biomaterials resulting in different local concentrations of released vancomycin. Overall, the biphasic release profiles of vancomycin from ECnVs/co-gel and ECnVs/ collagen more effectively inhibited the growth of MRSA for 18 and 24 h, respectively, even after repeated bacterial inoculation, as compared to matrices containing free vancomycin, which just delayed the growth of MRSA. Thus, this newly developed antibiotic delivery system exhibited distinct advantages for controlled vancomycin delivery and prolonged antibacterial activity relevant to the treatment of wound infections.

VEGF-Encoding, Gene-Activated Collagen-Based Matrices Promote Blood Vessel Formation and Improved Wound Repair

“…This formulation process does not employ covalent crosslinking between collagen and HA, which enables a similar collagen fibrillar structure in all samples (as assessed via microscopy analysis of the samples under reflected light at a wavelength of 405 nm, and by microscopic analysis of the autofluorescence of the collagen fibers) . We expect that the range of storage moduli of the samples would be below 100 Pa based on measurements of the storage moduli of collagen (54 Pa) and collagen and fibrin (61 Pa) hydrogels in our prior studies . After gelation at 37 °C for 45 min, the samples were incubated in complete DMEM at 37 °C with 5% CO 2 for 7 days.…”

“…25 We expect that the range of storage moduli of the samples would be below 100 Pa based on measurements of the storage moduli of collagen (54 Pa) and collagen and fibrin (61 Pa) hydrogels in our prior studies. 27 After gelation at 37 °C for 45 min, the samples were incubated in complete DMEM at 37 °C with 5% CO 2 for 7 days. The culture medium was collected and replaced with fresh culture medium every 2 days.…”

Nanoarchitecture-Integrated Hydrogel Systems toward Therapeutic Applications

“…Bioactive peptides can bind noncovalently to produce a diversity of supramolecular assemblages including nanoparticles and nanofibers, thus enhancing in vivo stability and bioavailability. Based on these characters, a large number of supramolecular assemblages have been extensively designed to form hydrogel and integrate with nanoarchitectures for extending bioapplication. − For instance, a self-assembled chelating peptide hydrogel (PPH) was engineered to load with an osteogenic metal ion cluster extracted from the processed pyritum decoction . Since this PPH could regulate a variety of genes related to extracellular matrix synthesis, cell adhesion and migration, and cytokine expression in the process of bone regeneration, PPH would accelerate the progress of various bone healing stages and shorten the bone healing cycle.…”

Analysis of Homo- and Heterotriple Helix Formation of Collagen Model Peptides and Evaluation of Their Stability in a Biological Environment

“…Various CMPs have been investigated as drug delivery carriers, thermosensitive gelators, collagen modification tools, and supramolecular assemblies due to their unique thermoresponsive triple helix formation and collagen binding properties via hydrogen bonding. − For example, a thermoresponsive gelator, a CMP-modified 8-arm PEG multiarm polymer, has been reported in a study using CMP as a cross-linking site . Previously, we also reported that multiarm poly­(ethylene glycol) (PEG) (4-arm-PEG-(POG) 10 ) end-modified with (POG) 10 induces gelation by binding between triple helices when mixed with fibrous collagen and has potential for tissue engineering applications .…”