Tabriz University of Medical Sciences Advanced Pharmaceutical Bulletin 2228-5881 14 1 2024 03 07 Green Formulation of Spironolactone Loaded Chitosan-Coated Nano Lipid Carrier for Treatment of Acne Vulgaris: A Randomized Double-Blind Clinical Trial 161 175 10.34172/apb.2024.011 EN Majid Saeedi https://orcid.org/0000-0003-2617-9961 Katayoun Morteza-Semnani Jafar Akbari Zohreh Hajheydari Amin Goodarzi Seyyed Sohrab Rostamkalaei Seyyed Mohammad Hassan Hashemi https://orcid.org/0000-0003-1148-180X Seyyed Mobin Rahimnia https://orcid.org/0000-0003-1499-7668 Journal Article 10.34172/apb.2024.011 2023 04 04 2023 09 20 Purpose: Spironolactone (SPN), which is classified as an anti-androgen, has demonstrated efficacy in treating acne. This study aimed to utilize ultrasonication to create a chitosan-coated nano lipid carrier (NLC) for enhancing the delivery of SPN to the skin and treating acne. Methods: Various hydrophilic-lipophilic balance (HLB) values were investigated to optimize the SPN-NLCs. Photon correlation spectroscopy, attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), transmission electron microscopy (TEM), and differential scanning calorimetry (DSC) were employed to characterize the solid state of SPN in nanoparticle form. Additionally, the optimized formulation was used in a double-blind, randomized clinical trial. Results: Reducing the HLB of the surfactant mixtures resulted in a reduction in the size of SPNNLCs. The formula with the smallest particle diameter (238.4±0.74 nm) and the lowest HLB value (9.65) exhibited the highest encapsulation efficiency (EE) of 79.88±1.807%. Coating the optimized SPN-NLC with chitosan increased the diameter, polydispersity index (PDI), zeta potential (ZP), and EE. In vitro skin absorption studies demonstrated sustained release profiles for chitosan-coated SPN-NLC. In the double-blind trial, a gel containing chitosan-coated SPN-NLC effectively treated mild to moderate acne vulgaris, leading to improved healing and reduced lesion count after 8 weeks of therapy compared to the placebo. It successfully addressed both non-inflammatory and inflammatory lesions without adverse effects on the skin. Conclusion: The findings indicate that chitosan-coated SPN-NLCs have the potential as nanoparticles for targeted SPN delivery to the skin, offering novel options for the treatment of acne vulgaris.