A rapid drug release system with a NIR light-activated molecular switch for dual-modality photothermal/antibiotic treatments of subcutaneous abscesses

J Control Release. 2015 Feb 10:199:53-62. doi: 10.1016/j.jconrel.2014.12.011. Epub 2014 Dec 11.

Abstract

Eradicating subcutaneous bacterial infections remains a significant challenge. This work reports an injectable system of hollow microspheres (HMs) that can rapidly produce localized heat activated by near-infrared (NIR) light and control the release of an antibiotic via a "molecular switch" in their polymer shells, as a combination strategy for treating subcutaneous abscesses. The HMs have a shell of poly(d,l-lactic-co-glycolic acid) (PLGA) and an aqueous core that is comprised of vancomycin (Van) and polypyrrole nanoparticles (PPy NPs), which are photothermal agents. Experimental results demonstrate that the micro-HMs ensure efficiently the spatial stabilization of their encapsulated Van and PPy NPs at the injection site in mice with subcutaneous abscesses. Without NIR irradiation, the HMs elute a negligible drug concentration, but release substantially more when exposed to NIR light, suggesting that this system is suitable as a photothermally-responsive drug delivery system. The combination of photothermally-induced hyperthermia and antibiotic therapy with HMs increases cytotoxicity for bacteria in abscesses, to an extent that is greater than the sum of the two treatments alone, demonstrating a synergistic effect. This treatment platform may find other clinical applications, especially for localized hyperthermia-based cancer therapy.

Keywords: Antibiotic therapy; Combination therapy; Hyperthermia; In situ drug delivery; Photothermal response system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abscess / drug therapy
  • Abscess / therapy*
  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Drug Delivery Systems*
  • Hot Temperature
  • Infrared Rays
  • Injections, Subcutaneous
  • Lactic Acid
  • Methicillin-Resistant Staphylococcus aureus / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Microspheres
  • Nanoparticles
  • Photochemistry
  • Polyglycolic Acid
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Pyrroles
  • Skin Diseases / drug therapy
  • Skin Diseases / therapy*
  • Tissue Distribution
  • Vancomycin / administration & dosage
  • Vancomycin / pharmacology
  • Vancomycin / therapeutic use
  • Wound Healing / drug effects

Substances

  • Anti-Bacterial Agents
  • Pyrroles
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Vancomycin