Sustained delivery of lidocaine into the cochlea using poly lactic/glycolic acid microparticles.
OBJECTIVE
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.


METHODS
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. Nystagmus 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.
Horie
Rie T
RT
Department of Otolaryngology, Head and Neck Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
Sakamoto
Tatsunori
T
Nakagawa
Takayuki
T
Tabata
Yasuhiko
Y
Okamura
Noboru
N
Tomiyama
Naoki
N
Tachibana
Mitsuhiro
M
Ito
Juichi
J
D000779:Anesthetics, Local / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D000818:Animals; D001672:Biocompatible Materials; D003051:Cochlea; D004337:Drug Carriers / Q000009:adverse effects; D016503:Drug Delivery Systems; D004432:Ear, Middle / Q000187:drug effects / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D019344:Lactic Acid / Q000009:adverse effects; D008012:Lidocaine / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008863:Microspheres; D011100:Polyglycolic Acid / Q000009:adverse effects; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D013499:Surface Properties; D014724:Vestibular Function Tests
D000779:Anesthetics, Local; D001672:Biocompatible Materials; D004337:Drug Carriers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D008012:Lidocaine