With the increased occurrence of antibiotic-resistant bacteria, alternatives to classical antibiotics are urgently needed for treatment of various infectious diseases. Medicinal plant extracts are among the promising candidates due to their bioactive components. The aim of this study was to prepare niosome-encapsulated Echinacea angustifolia extract and study its efficacy against multidrug-resistant Klebsiella pneumoniae strains. Encapsulation was first optimized by Design of Experiments, followed by the empirical study. The obtained niosomes were further characterized for the size and morphology using dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Spherical niosomes had a diameter of 142.3 ± 5.1 nm, as measured by DLS. The entrapment efficiency (EE%) of E. angustifolia extract reached up to 77.1% ± 0.3%. The prepared niosomes showed a controlled drug release within the tested 72 h and a storage stability of at least 2 months at both 4 and 25 °C. The encapsulated E. angustifolia displayed up to 16-fold higher antibacterial activity against multidrug-resistant K.pneumoniae strains, compared to the free extract. Additionally, the niosome exhibited negligible cytotoxicity against human foreskin fibroblasts. We anticipate that the results presented herein could contribute to the preparation of other plant extracts with improved stability and antibacterial activity, and will help reduce the overuse of antibiotics by controlled release of natural-derived drugs.

Non-healing wounds impose huge cost on patients, healthcare, and society, which are further fortified by biofilm formation and antimicrobial resistance (AMR) problems. Here, Thymol, an herbal antimicrobial agent, is utilized to combat AMR. For efficient delivery of Thymol gelatin methacryloyl (GelMa), a hydrophilic polymeric hydrogel with excellent biocompatibility combined with niosome was used to encapsulate Thymol. After optimization of the niosomal Thymol (Nio–Thymol) in the company of GelMa (Nio–Thymol@GelMa) to achieve maximum entrapment efficiency, minimum size, and low polydispersity index, the Thymol release peaked at 60% and 42% from Nio–Thymol@GelMa in medium with pH values of 6.5 and 7.4 after 72 h, respectively. Furthermore, Nio–Thymol@GelMa demonstrated higher antibacterial and anti-biofilm activity than Nio–Thymol and free Thymol against both Gram-negative and Gram-positive bacteria. Interestingly, compared with other obtained formulations, Nio–Thymol@GelMa also led to greater enhancement of migration of human dermal fibroblasts in vitro, and higher upregulation of the expression of certain growth factors such as FGF-1, and matrix metalloproteinases such as MMP-2 and MMP-13. These results suggest that Nio–Thymol@GelMa can represent a potential drug preparation for Thymol to enhance the wound healing process and antibacterial efficacy.