Green formulation, characterization, antifungal and biological safety evaluation of terbinafine HCl niosomes and niosomal gels manufactured by eco-friendly green method

Abstract

Terbinafine (TER) is a promising candidate medication for the topical treatment of fungal infections. However, its solubility in water and skin permeability are limited. To overcome these limitations, a Terbinafine niosome and niosomal gel was developed. The impact of cholesterol:surfactants on terbinafine incorporated niosome (terbinasome) preparations was examined. Differential scanning calorimetry (DSC), photon correlation spectroscopy (PCS), scanning electron microscopy (SEM), and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy were used to assess the morphological features of terbinasome and the physicochemical characteristics of TER in terbinasome. The obtained results has shown that Chol enhanced the diameter of the terbinasome from 123.20 ± 2.86 to 701.93 ± 17.72 nm. The highest encapsulation of terbinafine was estimated to be around 66% due to the cholesterol:surfactants ratio in the terbinasome was 1:3 and 1:6. Additional examination has revealed that changes in the cholesterol:surfactants ratio can result in a change in the PDI value of between 0.421 ± 0.004 and 0.712 ± 0.011. The terbinasome gel was prepared and tested for pharmaceutical testing, including pH, viscosity, spreadability, and stability. The percentage of TER dissolution from terbinasome were determined more than 80% and showed quickest drug release. In a cutaneous permeability examination, the quantity of TER in the cutaneous layers and the receiver compartment were higher for the terbinasome gel than for the TER simple gel. The terbinasome's cell viability was around 90% (HFF cell line) and MTT experiment demonstrated that the terbinasome was not cytotoxic. The MIC of the terbinasome was lower than pure drug against Aspergillus, Fusarium, and Trichophyton. The terbinasomal gels were non-irritant (score < 2) in the cutaneous irritation examination performed on Wistar rats. The research suggests that the optimized terbinasome may be used as a nano-vesicle for TER drug administration, hence opening up new possibilities for the treatment of cutaneous infections.

Keywords:

• Terbinafine
• niosome
• fungicide
• nanoparticle
• MTT
• irritation test

Acknowledgment

The authors would wish to express their sincere and special appreciation to research council of Mazandaran University of Medical Sciences, Sari, Iran, for their valuable and technical cooperation

Disclosure statement

No potential conflict of interest was reported by the authors.

CRediT authorship contribution statement

Katayoun Morteza-Semnani: Supervision, Writing – Review & Editing

Majid Saeedi: Supervision, Writing – Review & Editing

Jafar Akbari: Supervision

Shakiba Hedayati: Methodology, Investigation

Seyyed Mohammad Hassan Hashemi: Methodology, Investigation, Writing – Review & Editing, Writing – Original Draft Preparation

Seyyed Mobin Rahimnia: Methodology, Investigation

Amirhossein Babaei: Methodology, Investigation, Writing – Review & Editing

Mona Ghazanfari: Methodology, Investigation

Iman Haghani: Methodology, Investigation

Mohammad Taghi Hedayati: Supervision

Additional information

Funding

This study was funded by a grant number 11692 from the Mazandaran University of Medical Sciences Research Council, Sari, Iran with ethical code IR.MAZUMS.RIB.REC.1400.097.