The preparation of dexamethasone sodium phosphate multivesicular liposomes thermosensative hydrogel and its impact on noise-induced hearing loss in the Guinea …

Y Li, R Zhang, X Li, W Li, Y Lu, C Dai - Experimental Cell Research, 2020 - Elsevier
Y Li, R Zhang, X Li, W Li, Y Lu, C Dai
Experimental Cell Research, 2020Elsevier
Objective The aim of this study is to establish the dexamethasone sodium phosphate
multivesicular liposomes thermosensative hydrogel (DEX-MVLs-Gel) drug delivery system
and to analyze the pharmacodynamics, pharmacokinetics and safety of DEX-MVLs-Gel as
well as to explore whether the prepared DEX-MVLs-Gel can protect the hearing in the
guinea pigs following noise exposure. Methods DEX-MVLs formulations were constructed
by double emulsion method, and the DEX-MVLs-Gel was prepared after adding P407 and …
Objective
The aim of this study is to establish the dexamethasone sodium phosphate multivesicular liposomes thermosensative hydrogel (DEX-MVLs-Gel) drug delivery system and to analyze the pharmacodynamics, pharmacokinetics and safety of DEX-MVLs-Gel as well as to explore whether the prepared DEX-MVLs-Gel can protect the hearing in the guinea pigs following noise exposure.
Methods
DEX-MVLs formulations were constructed by double emulsion method, and the DEX-MVLs-Gel was prepared after adding P407 and P188 into the DEX-MVLs. A total of 20 adult albino guinea pigs were chosen to establish the animal models with noise-induced hearing loss. After animals were treated with DEX-MVLs-Gel at concentrations of 20, 6 and 2 mg/mL, and 5 mg/mL Dexamethasone Sodium Phosphate (DEX-P) solution, respectively, the hearing function, drug concentration in the peripheral lymph fluid, and hair cell morphology were assessed.
Results
The ABR threshold of the 20 mg/mL DEX-MVLs-Gel treated group at the frequencies of 4, 8, 16 and 24 kHz were measured as 47.5 ± 5.2, 48.3 ± 4.1, 55.8 ± 3.8 and 57.5 5 ± 5.2 dB SPL, respectively. Statistical significances were noted between the 20 mg/mL DEX-MVLs-Gel treated group and control group at each frequency (all P < 0.05), between the 2 mg/mL and 6 mg/mL DEX-MVLs-Gel treated groups at the frequencies of 4 and 8 kHz (both P < 0.05). High Performance Liquid Chromatography (HPLC) demonstrated that the drug concentrations in the peripheral lymph in all groups were gradually decreased on the 1st, 3rd and 7th d after intratympanic injection. Scattered hair cell loss could be observed mainly in the basal and middle turn in the saline administrated group and the 20 mg/mL DEX-MVLs-Gel administration group, and the hair cell loss was not identified in the apical turn.
Conclusions
A high concentration (20 mg/mL) of DEX-MVLs-Gel exerts significant protective effects upon the guinea pigs with noise-induced hearing loss. The prepared DEX-MVLs-Gel can be effectively maintained in the peripheral lymph fluid of guinea pigs for 3–7 d and MVLs-Gel causes no obvious ototoxicity.
Elsevier
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