Poly(caprolactone)-based subcutaneous implant for sustained delivery of levothyroxine
Open accessAbstract
This work aimed to develop a subcutaneous implant for prolonged delivery of LEVO to treat hypothyroidism. This could overcome challenges with patient compliance and co-administration and could improve treatment of this condition. For this purpose, implants were produced by solvent casting mixtures of poly(caprolactone) (PCL), poly(ethylene glycol) (PEG) and LEVO sodium. These implants contained mixtures of PCL of differing molecular weight, PEG and different LEVO sodium loadings (20% or 40% w/w). SEM images confirmed that the drug was evenly dispersed throughout the implant. In vitro release rates ranging from 28.37 ± 1.19 - 78.21 ± 19.93 µg/day and 47.39 ± 8.76 - 98.92 ± 4.27 µg/day were achieved for formulations containing 20% and 40% w/w drug loading, respectively. Implants containing higher amounts of low molecular weight PCL and 40% w/w of LEVO showed release profiles governed by zero order kinetics. On the other hand, implants containing higher amounts of high molecular weight PCL showed a release mechanism governed by Fickian diffusion. Finally, two representative formulations were tested in vivo. These implants were capable of providing detectable LEVO levels in plasma during the entire duration of the experiments (4 weeks) with LEVO plasma levels ranging between 5 and 20 ng/mL.
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A cumulative percentage of 8% to 20% was revealed after 98 days in vitro.
“A cumulative percentage of 8% to 20% was revealed after 98 days in vitro.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
An increased proportion of L-PCL in the ingredients increased drug loadings by 20% to 25%.
“An increased proportion of L-PCL in the ingredients was observed to increase the drug loadings by 20% to 25%.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
An implant made of 100% H-PCL could load approximately 40 mg LT4.
“An implant made of 100% H-PCL could load ∼40 mg LT4.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
Polyethylene glycol was incompatible with LT4 and caused significant drug degradation.
“Frustratingly, it was incompatible with LT4 and caused significant drug degradation.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
An in vitro study in bovine serum albumin solution revealed a linear release after a burst release in the first 24 hours.
“An in vitro study in bovine serum albumin solution revealed a linear release after a burst release in the first 24 hours.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
The average release rate was 30 to 100 μg/day and was close to the oral dose of LT4.
“The average release rate was 30 to 100 µg/day and was close to the oral dose of LT4 (44).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
The addition of L-PCL could prevent unwanted fast release over the first 24 hours.
“The addition of L-PCL could prevent unwanted fast release over this period.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
A large proportion of articles on LT4 nanomaterials only extended the studies to in vitro experiments and few proceeded to animal or human studies.
“However, a large proportion of articles only extended the studies to in vitro experiments and few of them proceeded to animal or human studies (179, 180, 272).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
The pharmacokinetic properties and biocompatibility of LT4 nanomaterials remained untested.
“The pharmacokinetic properties and biocompatibility remained untested.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [272]
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Levothyroxine: conventional and novel drug delivery formulations.
Liu, H., Li, W., Zhang, W., Sun, S., & Chen, C. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnac030 · Cited by 63 · see citing works
- Authors
- Stewart, S. A., Domínguez-Robles, J., Utomo, E., Picco, C. J., Corduas, F., Mancuso, E., Amir, M. N., Bahar, M. A., Sumarheni, S., Donnelly, R. F., Permana, A. D., & Larrañeta, E.
- Affiliations
- Queen's University Belfast (GB)
- University of Ulster (GB)
- Hasanuddin University (ID)
- Corresponding author
- Permana, Andi Dian
- Larrañeta, Eneko
- ORCID
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2021-09
- Volume
- 607
- Pages
- 121011
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W3196166366
- Cited by
- 35
- References
- 50
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 10 · 2023: 9 · 2022: 9 · 2021: 2
- FWCI
- 3.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Research Portal (Queen's University Belfast) (publishedVersion, cc-by-nc-nd)
- Ulster University Research Portal (Ulster University) (acceptedVersion, other-oa)
- Funders
- Department for the Economy
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Physical Sciences › Materials Science › Biomaterials › biodegradable polymer synthesis and properties
- Keywords
- levothyroxine, subcutaneous implants, polycaprolactone, sustained drug release, hypothyroidism, polyethylene glycol, solvent casting, Fickian diffusion, zero-order release kinetics, in vivo drug delivery, plasma drug concentration
- MeSH terms
- Drug Compounding, Humans, Polyesters, Polyethylene Glycols, Thyroxine
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