Formation of ion pairing as an alternative to improve encapsulation and stability and to reduce skin irritation of retinoic acid loaded in solid lipid nanoparticles
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This work aims to investigate the influence of the formation of ion pairing between all-trans retinoic acid (RA) and a lipophilic amine (stearylamine; STE) on the drug encapsulation efficiency (EE) and stability of solid lipid nanoparticles (SLNs). The SLNs were characterized for EE and size. The EE and particle size were significantly improved and reduced, respectively, when the surfactant or co-surfactant concentration increased. However, while the formulation without STE allowed only 13% of RA encapsulation, the EE for RA-STE-loaded SLNs was 94%. The stability studies showed a significant decrease in EE for the SLNs without STE, while, for SLNs loaded with RA and STE, the EE remained constant after 360 days. The interactions among ion pairing components and the lipid matrix were investigated through small-angle X-ray scattering (SAXS). The SAXS analysis revealed the presence of RA in the crystalline form in SLNs without ion pairing, while crystalline RA was not observed in SLNs loaded with RA/amine. Skin irritation studies showed that the SLNs loaded with the ion pairing were significantly less irritating when compared to the marketed RA-cream. This novel SLN formulation represents a promising alternative for topical treatment of acne with RA.
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Interaction of ATRA with a lipophilic amine (stearylamine) decreases ATRA crystallinity, leading to a formulation with less skin irritating properties.
“Interaction of ATRA with a lipophilic amine (stearylamine) decreases ATRA crystallinity, leading to a formulation with less skin irritating properties77.”
From Advances and challenges in retinoid delivery systems in regenerative and therapeutic medicine (2020) · cites this paper as [77]
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- Authors
- Castro, G. A., Coelho, A. L. L. R., Oliveira, C. A., Mahecha, G. A. B., Oréfice, R. L., & Ferreira, L. A. M.
- Affiliations
- Universidade Federal de Minas Gerais (BR)
- Corresponding author
- Ferreira, Lucas A.M.
- Venue
- International Journal of Pharmaceutics
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 381
- Issue
- 1
- Pages
- 77-83
- ISSN
- 0378-5173 (ISSN-L)
- OpenAlex
- W2005760281
- Cited by
- 119
- References
- 28
- Citations by year
- 2025: 6 · 2024: 8 · 2023: 3 · 2022: 4 · 2021: 14 · 2020: 10 · 2019: 9 · 2018: 5 · 2017: 7 · 2016: 8 · 2015: 11 · 2014: 6 · 2013: 9 · 2012: 8
- FWCI
- 4.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- International Journal of Pharmaceutics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Universidade Federal de Minas Gerais
- Laboratório Nacional de Luz Síncrotron
- 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
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- ion pairing, all-trans retinoic acid, solid lipid nanoparticles, octadecylamine, encapsulation efficiency, nanoparticle stability, skin irritation, topical retinoids, acne treatment
- MeSH terms
- Acne Vulgaris, Administration, Cutaneous, Amines, Animals, Chemistry, Pharmaceutical, Drug Stability, Emulsions, Exanthema, Excipients, Female, Mice, Hairless, Particle Size, Surface Properties, Surface-Active Agents, Tretinoin, X-Ray Diffraction, Drug Delivery Systems, Phase Transition, Mice, Nanoparticles, Scattering, Small Angle, Electrochemical Techniques
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