Majid Saeedi
1,2 
, Katayoun Morteza-Semnani
3, Jafar Akbari
2, Zohreh Hajheydari
4, Amin Goodarzi
5, Seyyed Sohrab Rostamkalaei
6, Seyyed Mohammad Hassan Hashemi
7* , Seyyed Mobin Rahimnia
2,5* 1 Pharmaceutical Sciences Research Center, Haemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
2 Department of Pharmaceutics, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
3 Department of Medicinal Chemistry, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
4 Department of Dermatology, Boo Ali Sina (Avicenna) Hospital, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
5 Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.
6 Department of Pharmaceutics, Faculty of Pharmacy, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran.
7 Department of Pharmaceutics, Faculty of Pharmacy, Hormozgan University of Medical Sciences, Bandar Abbas, Iran.
Abstract
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.