Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear

详细信息    查看全文

• 作者：Naila El Kechai^a ; ^{naila.el-kechai@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Elisabeth Mamelle^b ; ^c ; ^{elisabeth.mamelle@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Yann Nguyen^b ; ^c ; ^{yann.nguyen@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Nicolas Huang^a ; ^{nicolas.huang@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Valé ; rie Nicolas^d ; ^{valerie.nicolas@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Pierre Chaminade^e ; ^{pierre.chaminade@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Sté ; phanie Yen-Nicolaÿ ; ^e ; ^{stephanie.nicolay@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Claire Gueutin^a ; ^{claire.gueutin@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Benjamin Granger^f ; ^{benjamin.granger@aphp.fr" class="auth_mail" title="E-mail the corresponding author} ; Evelyne Ferrary^b ; ^{evelyne.ferrary@inserm.fr" class="auth_mail" title="E-mail the corresponding author} ; Florence Agnely^a ; ¹ ; ^{florence.agnely@u-psud.fr" class="auth_mail" title="E-mail the corresponding author} ; Amé ; lie Bochot^a ; ¹ ; ^{amelie.bochot@u-psud.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Chol ; cholesterol ; DSPE-PEG2000 ; 1 ; 2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-poly-(ethyleneglycol)-2000] ; Dex ; dexamethasone ; DexP ; dexamethasone phosphate ; DLS ; dynamic light scattering ; EPC ; egg phosphatidylcholine ; Flu ; flumethasone ; HA ; hyaluronic acid ; Lip ; liposomes ; LC&ndash ; MS ; liquid chromatography coupled to mass spectroscopy ; PE ; phosphatidylethanolamine ; Rh ; rhodamine ; RW ; round window
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：28 March 2016
• 年：2016
• 卷：226
• 期：Complete
• 页码：248-257
• 全文大小：815 K

文摘

The inner ear is one of the most challenging organs for drug delivery, mainly because of the blood-perilymph barrier. Therefore, local rather than systemic drug delivery methods are being developed for inner ear therapy. In this work, we have evaluated the benefit of a hyaluronic acid liposomal gel for sustained delivery of a corticoid to the inner ear after local injection into the middle ear in a guinea pig model. The liposomal gel was easily injectable as a result of the shear-thinning behavior of hyaluronic acid. A prolonged residence time at the site of injection as well as in the round window were achieved without any negative effect on the hearing thresholds of the animals. The presence of liposomes in the formulation resulted in sustained release of the drug in the perilymph for 30 days and promoted the conversion of the prodrug loaded within the liposomes (dexamethasone phosphate) into its active form (dexamethasone). In this way, therapeutic doses were attained in the perilymph. A small amount of intact liposomes was visualized in the perilymph, whereas the main proportion of liposomes seemed to be trapped in the round window resulting in a reservoir effect. Thus, the administration of hyaluronic acid liposomal gel to the middle ear is an efficient strategy for delivering corticoids to the inner ear in a sustained manner.