Sustained Delivery of Lidocaine Into the Cochlea Using Poly Lactic/Glycolic Acid Microparticles

被引:44
作者
Horie, Rie T.
Sakamoto, Tatsunori
Nakagawa, Takayuki [1 ]
Tabata, Yasuhiko [4 ]
Okamura, Noboru [5 ]
Tomiyama, Naoki [5 ]
Tachibana, Mitsuhiro [2 ,3 ]
Ito, Juichi
机构
[1] Kyoto Univ, Grad Sch Med, Dept Otolaryngol Head & Neck Surg, Sakyo Ku, Kyoto 6068507, Japan
[2] Kyoto Univ, Dept Pathol & Biol Dis, Kyoto 6068507, Japan
[3] Kyoto Univ, Dept Diagnost Pathol, Grad Sch Med, Kyoto 6068507, Japan
[4] Kyoto Univ, Inst Frontier Med Sci, Dept Biomat, Kyoto 6068507, Japan
[5] Mukogawa Womans Univ, Dept Pharmaceut Sci, Nishinomiya, Hyogo, Japan
关键词
Biomaterial; drug-delivery system; inner ear; poly lactic/glycolic acid; tinnitus; INNER-EAR; TINNITUS; BEHAVIOR; THERAPY;
D O I
10.1002/lary.20713
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Objectives/Hypothesis: Lidocaine is a local anesthetic that is known to suppress tinnitus via systemic or local application; however, this effect has only limited duration. The current study aimed to establish a method for the sustained delivery of lidocaine into the cochlea using poly lactic/glycolic acid (PLGA) microparticles. Study Design: Experimental study. Methods: Lidocaine-loaded PLGA microparticles were produced and their in vitro-release profiles were examined. The lidocaine concentrations in the perilymph were measured at different time points following the application of the lidocaine-loaded PLGA microparticles to the round-window membranes of guinea pigs. The possible adverse effects of the local application of lidocaine-loaded PLGA microparticles were also examined. Results: The in vitro analyses revealed that the microparticles were capable of the sustained delivery of lidocaine. The in vivo experiments demonstrated the sustained delivery of lidocaine into the cochlear fluid, and the maintenance of high lidocaine concentrations in the perilymph for up to 3 days after application. Nyptagmus and inflammation in the middle ear mucosa were not detected after the local application of lidocaine-loaded PLGA microparticles, although temporary hearing loss was observed. Conclusions: Lidocaine-loaded PLGA microparticles were shown to be capable of the sustained delivery of lidocaine into the cochlea, suggesting that they could be used for the attenuation of peripheral tinnitus.
引用
收藏
页码:377 / 383
页数:7
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