[In vitro dexamethasone release from nanoparticles and its pharmacokinetics in the inner ear after administration of the drug-loaded nanoparticles via the round window].
OBJECTIVE
To investigate the feasibility of local drug delivery into the inner ear using solid lipid nanoparticles (SLN) and evaluate its potential for inner ear disease treatment in terms of the pharmacokinetics of the delivered drug in the inner ear.


METHODS
Dexamethasone acetate (DA)-loaded SLN was prepared with Compritol 888 ATO as the matrix by means of hot dispersion-ultrasonic technique. A high-performance liquid chromatography (HPLC) was established for determining DA and dexamethasone (Dex). The pharmaceutical properties of DA-loaded SLN including the particle size, entrapment ratio and in vitro release were estimated. DA-loaded SLN was administered via intratympanic injection or intravenous injection in guinea pigs and Dex concentration in the perilymph was measured with HPLC for estimation of the pharmacokinetic parameters.


RESULTS
The mean diameter of the DA-loaded SLN was 106.8 nm with entrapment ratio of 83.8%, and the in vitro DA release from the nanoparticles well conformed to Weibull distribution, with sustained-release of DA from the SLN exceeding 6 days. After intravenous injection of DA-loaded SLN in guinea pigs, Dex failed to be detected in the perilymph. Compared with Dex-loaded in situ gel following intratympanic injection, the relative bioavailability of Dex in the perilymph was 504% following intratympanic injection of DA-loaded SLN, which also resulted in increased t(1/2) and mean residence time (MRT) by 0.5 and 1.9 folds respectively.


CONCLUSIONS
Nanoparticles can be a promising tympanic drug delivery system for topical drug administration in the treatment of inner ear diseases.
Chen
Gang
G
Department of Pharmaceutical Sciences, Guangdong Pharmaceutical University, Guangzhou 510006, China. cg753@126.com
Hou
Shi-Xiang
SX
Hu
Ping
P
Hu
Qiao-Hong
QH
Guo
Dan-Dan
DD
Xiao
Yu
Y
D000287:Administration, Topical; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007758:Ear, Inner / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D008297:Male; D053758:Nanoparticles / Q000008:administration & dosage*; D012405:Round Window, Ear / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D003907:Dexamethasone