Exploring the Synergistic Effect of Bergamot Essential Oil with Spironolactone Loaded Nano-Phytosomes for Treatment of Acne Vulgaris: In Vitro Optimization, In Silico Studies, and Clinical Evaluation

Abstract

The foremost target of the current work was to formulate and optimize a novel bergamot essential oil (BEO) loaded nano-phytosomes (NPs) and then combine it with spironolactone (SP) in order to clinically compare the efficiency of both formulations against acne vulgaris. The BEO-loaded NPs formulations were fabricated by the thin-film hydration and optimized by 32 factorial design. NPs’ assessments were conducted by measuring entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), and zeta potential (ZP). In addition, the selected BEO-NPs formulation was further combined with SP and then examined for morphology employing transmission electron microscopy and three months storage stability. Both BEO-loaded NPs selected formula and its combination with SP (BEO-NPs-SP) were investigated clinically for their effect against acne vulgaris after an appropriate in silico study. The optimum BEO-NPs-SP showed PS of 300.40 ± 22.56 nm, PDI of 0.571 ± 0.16, EE% of 87.89 ± 4.14%, and an acceptable ZP value of −29.7 ± 1.54 mV. Molecular modeling simulations showed the beneficial role of BEO constituents as supportive/connecting platforms for favored anchoring of SP on the Phosphatidylcholine (PC) interface. Clinical studies revealed significant improvement in the therapeutic response of BEO-loaded NPs that were combined with SP over BEO-NPs alone. In conclusion, the results proved the ability to utilize NPs as a successful nanovesicle for topical BEO delivery as well as the superior synergistic effect when combined with SP in combating acne vulgaris.

Bergamot Byproducts: A Sustainable Source to Counteract Inflammation

“…The anti-inflammatory role of bergamot derivatives was also documented in vivo, considering that BJ improved the acne vulgaris lesions caused by an excessive secretion of androgen via reducing the release of inflammatory IL-1α, IL-6, TNF-α cytokines and the levels of matrix metalloprotease (MMP)-2 and -9 in the sebaceous gland of golden hamsters, though to a lesser extent than BEO [ 109 ]. This study is resulted in line with a previous clinical application in which a nano-phytosome (NP) formulation was developed to optimize the BEO topical delivery, experiencing synergic effects between BEO-NPs and spironolactone in acne patients [ 110 ]. Interestingly, ultradeformable nanocarriers were designed for a transdermal delivery of naturally derived compounds such as BEO and ammonium glycyrrhizinate (AG) since the proper deformability of these nanosystems facilitates movement through the skin barrier, ensuring a topical application.…”

Advances and Developments in Drug Repurposing; State of Art

“…Another study performed by Albash et al proved the enhanced repurposed effect of spironolactone for reducing hair production and as a treatment for hirsutism using hyaluronic acid enriched cerosomes 59 . Further, another study performed in human subjects proved the efficacy of the repurposed effect of spironolactone against acne using nanocarrier called phytosome 60 . Another investigation proved the efficacy of 3-D nanocompositealginate-hydrogel loaded with pitavastatin nanovesicles as a functional wound dressing with controlled drug release aspect 61 .…”

Metformin Loaded Zein Polymeric Nanoparticles to Augment Antitumor Activity against Ehrlich Carcinoma via Activation of AMPK Pathway: D-Optimal Design Optimization, In Vitro Characterization, and In Vivo Study

“…It was tested for visual, EE%, PS, PDI, and ZP alterations before and after storage. The gathered data were statistically examined utilizing the Student's t-test in SPSS ® program 22.0 [63,64] The current investigation was carried out in accordance with the guidelines for the care and use of laboratory animals approved by the Research Ethical Committee, Faculty of Pharmacy, October 6 University, Egypt (PRE-Ph-2212046). A total of 70 adult female Swiss Albino mice weighing 20-25 g were acquired from the National Research Center (Cairo, Egypt).…”