Development and characterization of skin permeation retardants and enhancers: a comparative study of levothyroxine-loaded PNIPAM, PLA, PLGA and EC microparticles
Abstract
Polymeric microparticles suitable for topical and transdermal delivery systems were studied using poly D,L lactide (PLA), poly D,L lactide co glycoside (PLGA), poly (N-isopropylacrylamide) (PNIPAM) and ethyl cellulose (EC). Drug encapsulation efficacy, microparticle stability and skin permeation studies of levothyroxine loaded microparticles were carried out using excised human skin, and the skin permeation pattern was observed using confocal laser scanning microscopy. It was found that ethyl cellulose microparticles had the highest drug encapsulation and minimal drug leakage during the 14 week storage period. The PNIPAM microparticles had the lowest drug encapsulation efficiency and a fast degradation rate. The PLGA microparticles exhibited a temperature dependent drug leakage. Permeation studies using a flow-through diffusion cell indicated that the polymer transition temperature (T(g)) may influence the skin permeation rate of levothyroxine. Polyesters (PLA and PLGA) and PNIPAM acted as a skin penetration retardant and caused skin accumulation of the drug. These microparticles have potential use in skin formulations containing sunscreens and other active ingredients that are meant to be concentrated on the skin surface. However, skin permeation was observed from EC microparticles, therefore such polymers may be used as carriers in transdermal formulations to help achieve therapeutic concentrations of the drug in the plasma.
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50% to 70% of LT4 was gradually released in vitro during the first 15 to 30 minutes, with the remainder released in the next 2 to 7 hours.
“However, 50% to 70% of LT4 was gradually released in vitro during the first 15 to 30 minutes, with the remainder being released in the next 2 to 7 hours, denoting an unsatisfying sustained-release profile.”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [266]
Azarbayjani et al. decreased LT4 skin permeability to almost an undetectable level by encapsulating LT4 into sustained-release nanoparticles.
“Azarbayjani et al further decreased the permeability to almost an undetectable level by encapsulating LT4 into sustained-release nanoparticles (266, 267).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [266]
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Levothyroxine: conventional and novel drug delivery formulations.
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- Authors
- Azarbayjani, A. F., Khu, J. V., Chan, Y. W., & Chan, S. Y.
- Affiliations
- National University of Singapore (SG)
- Singapore General Hospital (SG)
- Corresponding author
- Chan, Sui Yung
- Venue
- Biopharmaceutics & Drug Disposition
- Publisher
- Wiley
- Published
- 2011-08-03
- Volume
- 32
- Issue
- 7
- Pages
- 380-388
- ISSN
- 0142-2782 (ISSN-L)
- OpenAlex
- W1838357553
- Cited by
- 24
- References
- 40
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 3 · 2020: 2 · 2019: 3 · 2018: 1 · 2017: 1 · 2016: 2 · 2015: 3 · 2013: 2 · 2012: 1
- FWCI
- 0.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biopharmaceutics & Drug Disposition (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Funders
- National University of Singapore
- Universidad de la República Uruguay
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advancements in Transdermal Drug Delivery
- 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
- Keywords
- levothyroxine, polymeric microparticles, skin permeation, skin penetration enhancers, poly(N-isopropylacrylamide), poly(D,L-lactide), PLGA, ethyl cellulose, transdermal drug delivery, encapsulation efficiency, polymer degradation, glass transition temperature, confocal laser scanning microscopy, flow-through diffusion cell, topical formulation
- MeSH terms
- Polylactic Acid-Polyglycolic Acid Copolymer, Acrylic Resins, Cellulose, Drug Carriers, Drug Stability, Drug Storage, Humans, Microscopy, Electron, Scanning, Particle Size, Permeability, Polyesters, Polyglycolic Acid, Polymers, Skin, Thyroxine, Microscopy, Confocal, Lactic Acid
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