Enhancement of antifungal activity and transdermal delivery of 5-flucytosine via tailored spanlastic nanovesicles: statistical optimization, in-vitro characterization, and in-vivo biodistribution study

Awaji Y Safhi; Nimbagal Raghavendra Naveen; Krishna Jayanth Rolla; Penmetsa Durga Bhavani; Mallesh Kurakula; Khaled M Hosny; Walaa A Abualsunun; Mohammed Alissa; Abdullah Alsalhi; Amerh Aiad Alahmadi; Khalid Zoghebi; Abdulrahman Sindam Halwaani; Rasha Ibrahim K

doi:10.3389/fphar.2023.1321517

Enhancement of antifungal activity and transdermal delivery of 5-flucytosine via tailored spanlastic nanovesicles: statistical optimization, in-vitro characterization, and in-vivo biodistribution study

Front Pharmacol. 2023 Dec 4:14:1321517. doi: 10.3389/fphar.2023.1321517. eCollection 2023.

Affiliations

¹ Department of Pharmaceutics, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
² Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy, Adichunchanagiri University, Mandya, Karnataka, India.
³ Department of Biotechnology, Sri Indu Institute of Engineering, Hyderabad, Telangana, India.
⁴ Department of Pharmaceutics, Vishnu Institute of Pharmaceutical Education and Research, Narsapur, Telangana, India.
⁵ Thermo Fisher Scientific, Bend, OR, United States.
⁶ Department of Pharmaceutics, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
⁷ Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
⁸ Department of Pharmaceutical Chemistry, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
⁹ Central Lab for Neurosciences, King Abdulaziz University, Jeddah, Saudi Arabia.
¹⁰ Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt.

Abstract

Aim and background: This current study aimed to load 5-flucytosine (5-FCY) into spanlastic nanovesicles (SPLNs) to make the drug more efficient as an antifungal and also to load the 5-FCY into a hydrogel that would allow for enhanced transdermal permeation and improved patient compliance. Methods: The preparation of 5-FCY-SPLNs was optimized by using a central composite design that considered Span 60 (X1) and the edge activator Tween 80 (X2) as process variables in achieving the desired particle size and entrapment efficiency. A formulation containing 295.79 mg of Span 60 and 120.00 mg of Tween 80 was found to meet the prerequisites of the desirability method. The optimized 5-FCY-SPLN formulation was further formulated into a spanlastics gel (SPG) so that the 5-FCY-SPLNs could be delivered topically and characterized in terms of various parameters. Results: As required, the SPG had the desired elasticity, which can be credited to the physical characteristics of SPLNs. An ex-vivo permeation study showed that the greatest amount of 5-FCY penetrated per unit area (Q) (mg/cm²) over time and the average flux (J) (mg/cm²/h) was at the end of 24 h. Drug release studies showed that the drug continued to be released until the end of 24 h and that the pattern was correlated with an ex-vivo permeation and distribution study. The biodistribution study showed that the 99mTc-labeled SFG that permeated the skin had a steadier release pattern, a longer duration of circulation with pulsatile behavior in the blood, and higher levels in the bloodstream than the oral 99mTc-SPNLs. Therefore, a 5-FCY transdermal hydrogel could possibly be a long-acting formula for maintenance treatment that could be given in smaller doses and less often than the oral formula.

Keywords: 5-flucytosine; anti-fungal; biodistribution; gel; healthcare; nanospanlastics; optimization.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. The Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah, Saudi Arabia, funded this project under Grant No. RG-4-166-43.