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Trans-Tympanic Drug Delivery for the Treatment of Ototoxicity
Published on: March 16, 2018
A Tanshinone IIA loaded hybrid nanocomposite with enhanced therapeutic effect for otitis media
Hang Yu1, Pei Zeng1, Yongshi Liang1
1School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Provincial Key Laboratory of Advanced Drug Delivery, Guangdong Pharmaceutical University, Guangzhou 510006, PR China; Guangdong Provincial Engineering Center of Topical Precise Drug Delivery System, Guangdong Pharmaceutical University, Guangzhou 510006, PR China.
Abstract:
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.
Insights
A novel silver nanoparticle (AgNPs) hybrid nanocomposite, TSIIA @ CS/Lys @ AgNPs, effectively treats middle ear infections (otitis media) in guinea pigs. This innovative antibacterial approach shows comparable efficacy to ofloxacin with reduced toxicity and lower administration frequency.
Area of Science:
- Biomaterials Science
- Nanotechnology
- Pharmacology
Background:
- Otitis media (middle ear inflammation) is a common condition leading to hearing loss, often caused by Staphylococcus aureus.
- Increasing antibiotic resistance necessitates novel therapeutic strategies for bacterial infections.
- Current treatments face challenges with diminishing effectiveness due to emerging resistant bacterial strains.
Purpose of the Study:
- To design and fabricate a novel multicomponent hybrid nanocomposite for treating otitis media.
- To evaluate the antibacterial efficacy and therapeutic effect of the developed nanocomposite.
- To assess the safety and potential for reduced administration frequency of the new therapeutic system.
Main Methods:
- Fabrication of a silver nanoparticle (AgNPs)-based hybrid nanocomposite (TSIIA @ CS/Lys @ AgNPs) with chitosan (CS) or lysozyme (Lys) and Tanshinone IIA (TSIIA).
- Evaluation of therapeutic effect against acute otitis media in a guinea pig model.
- Assessment of the nanocomposite dispersed in a poly (lactic-co-glycolic acid)/N-methyl-2-pyrrolidone (PLGA/NMP) organogel formulation for in-situ application.
- Toxicity assessment on basilar membrane and epithelia tissue in healthy guinea pigs.
Main Results:
- The TSIIA @ CS/Lys @ AgNPs nanocomposite demonstrated significant therapeutic effects against acute otitis media, comparable to commercial ofloxacin.
- The organogel formulation maintained therapeutic effectiveness with a reduced injection frequency compared to solution formulations.
- No obvious toxicity was observed in healthy guinea pigs treated with the hybrid nanocomposite or organogel.
Conclusions:
- The developed hybrid nanocomposite offers an effective and safe strategy for treating otitis media.
- This approach enhances antibacterial efficacy and provides a promising alternative to conventional antibiotics.
- The study highlights a novel therapeutic system with potential for reduced administration frequency.

