Thyroid hormone (levothyroxine) replacement via the respiratory route by inhalation:in vitro exploratory studies
Abstract
OBJECTIVES: To conduct proof of principle studies that will enable development of noninvasive (respiratory) delivery systems for levothyroxine (T4). METHODS: Preformulation (solubility, stability), formulation and biopharmaceutical (in vitro absorption, transport, gene expression) studies were conducted. Calu-3 cell line was used for permeation studies. RESULTS: Solubility profiles of T4 were established in aqueous (PBS, HBSS, isotonic saline) and non-aqueous solvents (PEG 400, PEG 600, propylene glycol, glycerine). Transport of the compound across Calu-3 cells suggested involvement of active transport systems. This correlated with expression of thyroxine transporters (MCT8, MCT10, OATP1A2, LAT1 and LAT2) in the cell line. Diffusion characteristics showed significant absorption with no detection of T4 metabolite (triiodothyronine). Formulation studies revealed that stable formulations could be prepared using a combination of aqueous and non-aqueous solvents. CONCLUSIONS: Results of the studies indicated that T4 can be absorbed effectively from the respiratory mucosa. Factors affecting stability such as pH and temperature should be taken into account during formulation development of this compound for the respiratory route.
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A cumulative permeation of 0.90 ± 0.53 μM was achieved in the apical to basolateral direction at 37 °C over 3 hours for LT4 in Calu-3 respiratory mucosa cells.
“A cumulative permeation of 0.90 ± 0.53 µM was achieved in the apical to basolateral direction at 37 °C over 3 hours.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [263]
Real-time polymerase chain reaction showed expression of sodium-dependent thyroid hormone transporters on the apical membrane of Calu-3 cells, which were significantly affected by pH and temperature.
“Real-time polymerase chain reaction showed expression of sodium-dependent TH transporters on the apical membrane of Calu-3 cells, which were significantly affected by pH and temperature.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [263]
The respiratory epithelium is a promising route for LT4 administration without significant cytotoxicity.
“Their study denoted the respiratory epithelium as a promising route for LT4 administration without significant cytotoxicity.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [263]
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Levothyroxine: conventional and novel drug delivery formulations.
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- Authors
- Agu, R. U., Mactavish, J., K. Yeung, P., & Imran, S. A.
- Affiliations
- Dalhousie University (CA)
- Corresponding author
- Imran, Syed Ali
- Venue
- Expert Opinion on Drug Delivery
- Publisher
- Informa UK Limited
- Published
- 2015-12-18
- Volume
- 13
- Issue
- 2
- Pages
- 195-205
- ISSN
- 1742-5247 (ISSN-L)
- 1744-7593
- OpenAlex
- W2233665716
- Cited by
- 4
- References
- 29
- Citations by year
- 2024: 1 · 2022: 2 · 2019: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Opinion on Drug Delivery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- College of Pharmacy, Dalhousie University (PEF2012)
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Inhalation and Respiratory Drug Delivery
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Drug Solubulity and Delivery Systems
- Keywords
- levothyroxine, thyroid hormone replacement, pulmonary drug delivery, respiratory mucosa, Calu-3 cells, drug permeation, active transport, MCT8, MCT10, OATP1A2, LAT1, LAT2, drug solubility, drug stability, non-aqueous solvents, preformulation, drug formulation
- MeSH terms
- Administration, Inhalation, Carrier Proteins, Cell Line, Chemistry, Pharmaceutical, Humans, Hypothyroidism, Solvents, Thyroxine, Gene Expression, Respiratory Mucosa
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