Abstract
In the present study, a novel transdermal delivery system was developed and its advantages were demonstrated. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug; however, because of its short biological half-life, it must be frequently administered orally and is highly irritating to the digestive tract. To prepare a novel transdermal delivery system for ibuprofen, a microemulsion was used as a drug carrier and dispersed in a hyaluronic acid-based hydrogel (ME/Gel) to increase percutaneous drug absorption while avoiding gastrointestinal tract irritation. The prepared microemulsion had a droplet size of ~ 90 nm, and the microemulsion had good stability in the hydrogel. Rheological tests revealed that the ME/Gel is a pseudoplastic fluid with decreased viscosity and increased shear rate. It displayed a certain viscoelasticity, and the microemulsion distribution displayed minor effects on the rheological characteristics of the hydrogel system. There was no significant difference in the rheology of the ME/Gel at 25°C and 32°C (normal skin surface temperature), which is beneficial for clinical application. Drug transdermal flux was significantly higher than that of the hydrogel and commercial cream groups (p < 0.01). The 24-h cumulative drug permeation amount was 1.42-fold and 2.52-fold higher than that of the hydrogel and cream groups, respectively. By loading into the ME/Gel, the cytotoxicity of the drug to HaCaT cells was reduced. These results indicate that the prepared ME/Gel can effectively improve transdermal ibuprofen delivery and the biosafety of the drug and could therefore have applicability as a drug delivery system.
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Abbreviations
- IBU:
-
Ibuprofen
- HA:
-
Hyaluronic acid
- ME:
-
Ibuprofen-loaded microemulsion
- ME/Gel:
-
Ibuprofen-loaded microemulsion-based hyaluronic acid hydrogel
- Gel:
-
Ibuprofen-loaded hyaluronic acid hydrogel
- NS:
-
Normal saline
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All authors contributed to the experimental studies, data collection and statistical analysis, and the structuring and writing of the article.
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The data used to derive Fig. 3 and Fig. 5b in this work can be obtained upon reasonable request from the corresponding author.
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This work was financially supported by the National Natural Science Foundation of China (81673612, 81573619).
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Zhang, Y., Zhang, K., Wang, Z. et al. Transcutol® P/Cremophor® EL/Ethyl Oleate–Formulated Microemulsion Loaded into Hyaluronic Acid–Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen. AAPS PharmSciTech 21, 22 (2020). https://doi.org/10.1208/s12249-019-1584-8
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DOI: https://doi.org/10.1208/s12249-019-1584-8