A Tanshinone IIA Loaded Hybrid Nanocomposite with Enhanced Therapeutic Effect for Otitis Media.

Otitis media, commonly known as middle ear inflammation, is among one of the most common maladies and results in significant morbidity such as loss of hearing. In view of the bacteria invasion such as Staphylococcus aureus causes the majority forms of otitis media, drug treatment generally uses antibacterial by topical or systematic approach. However, the effectiveness of antibacterial is diminishing because of the rapid emergence of antibiotic-resistant bacterial strains. Here, we designed and fabricated a silver nanoparticle (AgNPs)-based multicomponent hybrid nanocomposite termed as TSIIA @ CS/Lys @ AgNPs, which was comprised of a AgNPs core, a chitosan (CS) or lysozyme (Lys) middle layer, and a Tanshinone IIA (TSIIA) inclusion outlayer. Coating of CS or Lys to AgNPs through electrostatic interaction probably produced a core-shell nanocomplex resembling the endocarp of walnut. This design could reduce the dosage of AgNPs while maintaining antibacterial activity possibly due to the favorable interactions between nanocomplex and bacteria. The deposition of Chinese herb active component TSIIA by inclusion complexation formed the out layer of hybrid nanocomposite towards an improved antibacterial performance, which showed a therapeutic effect against acute otitis media of guinea pig comparable to the clinical commercial-used ofloxacin administrated by injection. The hybrid nanocomposite, when dispersed in poly (lactic-co-glycolic acid)/N-methyl-2-pyrrolidone (PLGA/NMP) solution as an in-situ organogel, not only maintained the therapeutic effectiveness, but also possessed the advantage of lower injection frequency compared with solution formulation. In addition, no obvious toxicity to the basilar membrane and epithelia tissue was observed after the healthy guinea pigs were treated with hybrid nanocomposite or organogel. This study provides a promising strategy to develop hybrid nanocomposite with enhanced antibacterial efficacy and also opens a new way for the establishment of efficient therapeutic systems with reduced administration frequency as substitute of antibiotics to treat otitis media.