Cryptotanshinone (CPT) is an efficacious acne treatment, while niosomal hydrogel is a known effective topical drug delivery system that produces a minimal amount of irritation. Three-dimensional (3D) printing technologies have the potential to improve the field of personalized acne treatment. Therefore, this study endeavored to develop a 3D-printed niosomal hydrogel (3DP-NH) containing CPT as a topical delivery system for acne therapy. Specifically, CPT-loaded niosomes were prepared using a reverse phase evaporation method, and the formulation was optimized using a response surface methodology. In vitro characterization showed that optimized CPT-loaded niosomes were below 150 nm in size with an entrapment efficiency of between 67 and 71%. The CPT-loaded niosomes were added in a dropwise manner into the hydrogel to formulate CPT-loaded niosomal hydrogel (CPT-NH), which was then printed as 3DP-CPT-NH with specific drug dose, shape, and size using an extrusion-based 3D printer. The in vitro release behavior of 3DP-CPT-NH was found to follow the Korsmeyer-Peppas model. Permeation and deposition experiments showed significantly higher rates of transdermal flux, Q24, and CPT deposition (p < 0.05) compared with 3D-printed CPT-loaded conventional hydrogel (3DP-CPT-CH), which did not contain niosomes. In vivo anti-acne activity evaluated through an acne rat model revealed that 3DP-CPT-NH exhibited a greater anti-acne effect with no skin irritation. Enhanced skin hydration, wide inter-corneocyte gaps in the stratum corneum and a disturbed lipid arrangement may contribute towards the enhanced penetration properties of CPT. Collectively, this study demonstrated that 3DP-CPT-NH is a promising topical drug delivery system for personalized acne treatments.
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This study was funded by the Science and Technology Planning Project of Guangdong Province (grant no. 2017B090912005 and 2017A050506027), National Natural Science Foundation of China (grant no. 81874346 and 81573611), Natural Science Foundation of Guangdong Province (grant no. 2017A030310021), and the Science and Technology Program of Guangzhou (grant no. 201907010018 and 201807010053).
All animal experiments presented here were performed in accordance with the animal handling guidelines established by The Ministry of Science and Technology of the People’s Republic of China, and the procedures were approved by the Ethics Committee of Southern Medical University.
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Electronic Supplementary Material
The methods of TEWL measurements, histopathological examination, skin ultrastructure observation (transmission electron microscopy), enzyme-linked immunosorbent assay, and the results of CCD, characterization of the release media (PBS) of 3DP-CPT-NH, cell viability of HaCaT cells, HE staining of rat skin, ELISA, CPT deposition in the normal and oleic acid treated skin treated with 3DP-CPT-NH and TEWL measurements are given in the supplementary data.
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Wang, Z., Liu, L., Xiang, S. et al. Formulation and Characterization of a 3D-Printed Cryptotanshinone-Loaded Niosomal Hydrogel for Topical Therapy of Acne. AAPS PharmSciTech 21, 159 (2020). https://doi.org/10.1208/s12249-020-01677-1
- niosomal hydrogel
- topical drug delivery
- 3D printing
- personalized acne treatments