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Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.
Jeong, Min Young; Kim, Subin; Kim, Hye Rim; Jeon, Jiae; Won, Seong Su; Yang, Keum-Jin; Park, Jun Soo; Yang, In Gyu; Lee, Dong Geon; Myung, Jin Hyuk; Kim, Yoon-Gyoon; Jin, Sung Giu; Choi, Yong Seok; Kim, Dong-Kee; Kang, Myung Joo.
Afiliación
  • Jeong MY; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Kim S; Department of Otolaryngology, College of Medicine, The Catholic University of Korea. 64 Daeheung-ro, Jung-gu, Daejeon, 34943, Republic of Korea.
  • Kim HR; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Jeon J; Department of Otolaryngology, College of Medicine, The Catholic University of Korea. 64 Daeheung-ro, Jung-gu, Daejeon, 34943, Republic of Korea.
  • Won SS; Department of Otolaryngology, College of Medicine, The Catholic University of Korea. 64 Daeheung-ro, Jung-gu, Daejeon, 34943, Republic of Korea.
  • Yang KJ; Department of Otolaryngology, College of Medicine, The Catholic University of Korea. 64 Daeheung-ro, Jung-gu, Daejeon, 34943, Republic of Korea.
  • Park JS; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Yang IG; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Lee DG; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Myung JH; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Kim YG; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Jin SG; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Choi YS; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea.
  • Kim DK; Department of Otolaryngology, College of Medicine, The Catholic University of Korea. 64 Daeheung-ro, Jung-gu, Daejeon, 34943, Republic of Korea. Electronic address: cider12@catholic.ac.kr.
  • Kang MJ; College of Pharmacy, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, Chungnam 31116, Republic of Korea. Electronic address: kangmj@dankook.ac.kr.
Carbohydr Polym ; 345: 122546, 2024 Dec 01.
Article en En | MEDLINE | ID: mdl-39227091
ABSTRACT
Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dexametasona / Cóclea / Hidrogeles / Nanopartículas / Derivados de la Hipromelosa / Inyección Intratimpánica / Pérdida Auditiva Límite: Animals Idioma: En Revista: Carbohydr Polym Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dexametasona / Cóclea / Hidrogeles / Nanopartículas / Derivados de la Hipromelosa / Inyección Intratimpánica / Pérdida Auditiva Límite: Animals Idioma: En Revista: Carbohydr Polym Año: 2024 Tipo del documento: Article Pais de publicación: Reino Unido