title: Hyaluronic acid liposomal gel sustains delivery of a corticoid to the inner ear.
abstract: 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 30days 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.
authors: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: naila.el-kechai@u-psud.fr.
authors: Naila
authors: N
authors: El Kechai
authors: UMR-S 1159 Inserm/Université Pierre et Marie Curie - Sorbonne Universités "Minimally Invasive Robot-based Hearing Rehabilitation", 16 rue Henri Huchard, 75018 Paris, France; AP-HP, Pitié-Salpêtrière Hospital, Otolaryngology Department, Unit of Otology, Auditory Implants and Skull Base Surgery, 75013 Paris, France. Electronic address: elisabeth.mamelle@gmail.com.
authors: Elisabeth
authors: E
authors: Mamelle
authors: UMR-S 1159 Inserm/Université Pierre et Marie Curie - Sorbonne Universités "Minimally Invasive Robot-based Hearing Rehabilitation", 16 rue Henri Huchard, 75018 Paris, France; AP-HP, Pitié-Salpêtrière Hospital, Otolaryngology Department, Unit of Otology, Auditory Implants and Skull Base Surgery, 75013 Paris, France. Electronic address: yann.nguyen@inserm.fr.
authors: Yann
authors: Y
authors: Nguyen
authors: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: nicolas.huang@u-psud.fr.
authors: Nicolas
authors: N
authors: Huang
authors: UMS IPSIT, Plate-forme d'imagerie cellulaire, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: valerie.nicolas@u-psud.fr.
authors: Valérie
authors: V
authors: Nicolas
authors: UMS IPSIT, SAMM, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: pierre.chaminade@u-psud.fr.
authors: Pierre
authors: P
authors: Chaminade
authors: UMS IPSIT, SAMM, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: stephanie.nicolay@u-psud.fr.
authors: Stéphanie
authors: S
authors: Yen-Nicolaÿ
authors: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: claire.gueutin@u-psud.fr.
authors: Claire
authors: C
authors: Gueutin
authors: UPMC Univ Paris 06. AP-HP, Pitié Salpêtrière Hospital, Department of Public Health, 75013 Paris, France. Electronic address: benjamin.granger@aphp.fr.
authors: Benjamin
authors: B
authors: Granger
authors: UMR-S 1159 Inserm/Université Pierre et Marie Curie - Sorbonne Universités "Minimally Invasive Robot-based Hearing Rehabilitation", 16 rue Henri Huchard, 75018 Paris, France. Electronic address: evelyne.ferrary@inserm.fr.
authors: Evelyne
authors: E
authors: Ferrary
authors: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: florence.agnely@u-psud.fr.
authors: Florence
authors: F
authors: Agnely
authors: Institut Galien Paris-Sud, CNRS UMR 8612, Univ. Paris-Sud, Université Paris-Saclay, 92290 Châtenay-Malabry, France. Electronic address: amelie.bochot@u-psud.fr.
authors: Amélie
authors: A
authors: Bochot
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D007758:Ear, Inner / Q000378:metabolism*; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006168:Guinea Pigs; D006820:Hyaluronic Acid / Q000737:chemistry*; D007267:Injections; D008081:Liposomes / Q000737:chemistry*; D008297:Male
chemical_list: D003692:Delayed-Action Preparations; D005938:Glucocorticoids; D008081:Liposomes; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone; D006820:Hyaluronic Acid
keywords: 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-poly-(ethyleneglycol)-2000] (PubChem CID: 406952); Cholesterol (PubChem CID: 5997); Dexamethasone (PubChem CID: 5743); Dexamethasone phosphate; Dexamethasone sodium phosphate (PubChem CID: 16961); Liposomes; Local drug delivery; Local injection; Perilymph; Phosphatidylcholine (PubChem CID: 52922911); Round window; Sodium hyaluronate (PubChem CID: 3084049)