Antibiotic-loaded silica nanoparticles/collagen composite hydrogels with prolonged antimicrobial activity for wound infection prevention

C HÉLARY; GS ALVAREZ; AM MEBERT; X WANG; T CORADIN; MF DESIMONE

Kos

Conferencia; 5th International Conference on Tissue Engineering; 2014

[Oral] Cutaneous chronic wounds are characterized by an impaired wound healing after 6 weeks. In some cases, the absence of wound closure leads to infection and amputation. The most common bacteria responsible for the wound bed infection and biofilm formation are Pseudomonas aeruginosa and Staphylococcus aureus. Current treatments rely on negative pressure therapy or wound dressings. To date, no ideal treatment is available. Nowadays, research orientation is towards medicated dressings for drug delivery of antibiotics. Collagen-based biomaterials are broadly used to treat chronic wounds as collagen is biocompatible, biodegradable and favors wound healing. Nevertheless, collagen hydrogels are poor drug delivery systems since the drug content is usually released within a few minutes. Hence, the combination of collagen with a drug delivery system is required to control and delay the release. In this study, silica nanoparticles/collagen nanocomposites have been evaluated as novel drug delivery systems to prevent infection in chronic wounds. For this purpose, gentamycin, an antibiotic targeting gram positive and gram negative bacteria, was encapsulated within plain silica nanoparticles (SiNPs) of various sizes (100, 300 and 500 nm) using a single step procedure. Subsequently, increasing doses of loaded SiNPs were immobilized within concentrated collagen hydrogels. Silica nanoparticles of 500 nm in diameter presented the best loading capacity with 600 µg of gentamycin per SiNPs gram. Gentamycin-loaded 500 nm particles could be immobilized at high silica dose (250 mM) in concentrated collagen hydrogels without modifying their fibrillar structure or impacting on their biomechanical behavior (Figure 1A). Gentamycin release from the nanocomposites was sustained over 7 days, offering an unparalleled prolonged antibacterial activity on Pseudomonas aeuriginosa (Figure 1B and 1C). The drug release kinetic exhibited a linear profile without any initial burst. Particles immobilization within collagen hydrogels was not associated with any toxicity towards fibroblasts as cell viability was maximal despite the high SiNPs doses used. Taken together, our results show that nanocomposite hydrogels associating concentrated collagen hydrogels with gentamicin-loaded silica nanoparticles can be used as drug delivery systems for a prolonged antibacterial activity to treat chronic wounds.