Sustained delivery of triamcinolone acetonide from a thermosensitive microemulsion gel system for the treatment of sensorineural hearing loss
Intratympanic administration for the delivery of steroids has been extensively studied but limited because of low permeability of the drug through the row window membrane. Here, to effectively deliver poorly soluble triamcinolone acetonide (TA), microemulsions (ME) were prepared from Capmul MCM (oil), Cremophor RH40 (surfactant), and tetraglycol (cosurfactant) based on solubility studies, emulsifying ability test, and pseudoternary phase diagrams. Microemulsion gel (MEG) was prepared by mixing TA-ME with a poloxamer hydrogel base. The physicochemical properties of ME and MEG formulations were characterized, and the toxicity and oto-protective effectiveness were evaluated in vitro and in vivo. The ME-3 formulation showed a small droplet size (16.5 ± 0.2 nm), narrow PDI (0.067 ± 0.041), and enhanced TA solubility (2619.7 ± 57.6 μg/g). The optimized MEG demonstrated temperature-dependent gelation with a gelation time of 208 ± 10 sec at 37 °C. Slow degradation of the gel matrix sustained release of TA from MEG compared to the ME formulation. Both TA-ME and TA-MEG were found to be nontoxic to NIH3T3 cells at the test concentrations (0 to 5 µg/mL), and biocompatible after intratympanic administration to mice. The incorporation of ME into thermosensitive hydrogels prolonged retention of TA at the site of administration until 6 days. As a consequence, the enhanced drug absorption into the cochlea in TA-MEG group (approximately 2 times higher than other groups) protected hair cells, spiral ganglion neurons, and stria vascular cells from cisplatin-induced damage. Therefore, this injectable TA-loaded MEG is an effective and safe vehicle for the sustained delivery of triamcinolone acetonide into the inner ear.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:30 |
|---|---|
| Enthalten in: |
Drug delivery - 30(2023), 1 vom: 03. Dez., Seite 2242003 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Nguyen, Thu Nhan [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Emulsions |
|---|
| Anmerkungen: |
Date Completed 07.08.2023 Date Revised 09.08.2023 published: Print Citation Status MEDLINE |
|---|
| doi: |
10.1080/10717544.2023.2242003 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM360375863 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM360375863 | ||
| 003 | DE-627 | ||
| 005 | 20231226082902.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1080/10717544.2023.2242003 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1201.xml |
| 035 | |a (DE-627)NLM360375863 | ||
| 035 | |a (NLM)37537864 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Nguyen, Thu Nhan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Sustained delivery of triamcinolone acetonide from a thermosensitive microemulsion gel system for the treatment of sensorineural hearing loss |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 07.08.2023 | ||
| 500 | |a Date Revised 09.08.2023 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Intratympanic administration for the delivery of steroids has been extensively studied but limited because of low permeability of the drug through the row window membrane. Here, to effectively deliver poorly soluble triamcinolone acetonide (TA), microemulsions (ME) were prepared from Capmul MCM (oil), Cremophor RH40 (surfactant), and tetraglycol (cosurfactant) based on solubility studies, emulsifying ability test, and pseudoternary phase diagrams. Microemulsion gel (MEG) was prepared by mixing TA-ME with a poloxamer hydrogel base. The physicochemical properties of ME and MEG formulations were characterized, and the toxicity and oto-protective effectiveness were evaluated in vitro and in vivo. The ME-3 formulation showed a small droplet size (16.5 ± 0.2 nm), narrow PDI (0.067 ± 0.041), and enhanced TA solubility (2619.7 ± 57.6 μg/g). The optimized MEG demonstrated temperature-dependent gelation with a gelation time of 208 ± 10 sec at 37 °C. Slow degradation of the gel matrix sustained release of TA from MEG compared to the ME formulation. Both TA-ME and TA-MEG were found to be nontoxic to NIH3T3 cells at the test concentrations (0 to 5 µg/mL), and biocompatible after intratympanic administration to mice. The incorporation of ME into thermosensitive hydrogels prolonged retention of TA at the site of administration until 6 days. As a consequence, the enhanced drug absorption into the cochlea in TA-MEG group (approximately 2 times higher than other groups) protected hair cells, spiral ganglion neurons, and stria vascular cells from cisplatin-induced damage. Therefore, this injectable TA-loaded MEG is an effective and safe vehicle for the sustained delivery of triamcinolone acetonide into the inner ear | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Intratympanic delivery | |
| 650 | 4 | |a thermosensitive microemulsion gel | |
| 650 | 4 | |a triamcinolone acetonide | |
| 650 | 7 | |a Triamcinolone Acetonide |2 NLM | |
| 650 | 7 | |a F446C597KA |2 NLM | |
| 650 | 7 | |a Hydrogels |2 NLM | |
| 650 | 7 | |a Surface-Active Agents |2 NLM | |
| 650 | 7 | |a Emulsions |2 NLM | |
| 700 | 1 | |a Yoo, So-Yeol |e verfasserin |4 aut | |
| 700 | 1 | |a Tangchang, Warisraporn |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jae-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Son, Hwa-Young |e verfasserin |4 aut | |
| 700 | 1 | |a Park, Jeong-Sook |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Drug delivery |d 1996 |g 30(2023), 1 vom: 03. Dez., Seite 2242003 |w (DE-627)NLM09361134X |x 1521-0464 |7 nnns |
| 773 | 1 | 8 | |g volume:30 |g year:2023 |g number:1 |g day:03 |g month:12 |g pages:2242003 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1080/10717544.2023.2242003 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 30 |j 2023 |e 1 |b 03 |c 12 |h 2242003 | ||