Biofilm-related infections are increasing in health care, both in devices and non-device-related infections (Mirzaei et al., 2020). Most biofilms are tolerant to antibiotics and immune responses. Therefore, an urgent need is to find an alternative approach to antibiotics for inhibiting biofilm-related infection (Mirzaei et al., 2020). Biofilm can be overcome by inhibiting its formation or by dispersal/removal of the already formed biofilm (Shrestha et al., 2022). In general, antibiofilm agents include natural compounds, peptides, and extracellular polymeric substances (EPSs) degrading enzymes that target biofilm formation (Shrestha et al., 2022). Cinnamaldehyde, also known as Trans-Cinnamaldehyde, Cinnamal, or Cinnamic aldehyde, is the main component of cinnamon essential oil, naturally occurring in parts of cinnamon trees of Cinnamomum species (Firmino et al., 2018; Mohamed et al., 2018). Among essential oils, the antimicrobial potential was obtained from Cinnamomum cassia (C. cassia) and Cinnamomum zeylanicum (C. zeylanicum) (Firmino et al., 2018). C. cassia, traditionally known as “cinnamon-china,” is a permanent tree native to southern China (Luo et al., 2013). Generally, C. cassia is used in traditional Chinese medicine to treat illnesses such as diarrhea, cramps, lack of appetite, flatulent, gastric ulcers, cough, bronchitis, renal weakness, spasms, palpitation, arthritic angina, and fungal/bacterial infections of the skin (Chaudhry and Tariq, 2006; Firmino et al., 2018; Skidmore-Roth, 2009). C. zeylanicum is a native tree in some areas of India and Ceylon, known as “cinnamon-of-ceylon” (Lima et al., 2005). C. zeylanicum is used in folk medicine due to its various medicinal properties, including antiseptic, astringent, aperitif, aphrodisiac, stimulant and vasodilator, aromatic, sedative, carminative, digestive, antidiabetic antinociceptive, and diuretic (Firmino et al., 2018; Hassan et al., 2012). Many studies have proved the antimicrobial activities of cinnamaldehyde (Firmino et al., 2018; Khan et al., 2017; Mohamed et al., 2018). It was reported that cinnamaldehyde has antibiofilm activities against Gram-negative and Gram-positive bacteria, and yeasts (Firmino et al., 2018; Khan et al., 2017; Mohamed et al., 2018).
Additionally, it was reported that cinnamaldehyde can disrupt biofilm formation by reducing the expression of intracellular levels of c-di-GMP (Topa et al., 2018). Generally, high levels of c-di-GMP stimulate the expression of several adhesions and biofilm-associated exopolysaccharides (EPSs) and decrease the expression or activity of flagella (Hengge, 2009). Cinnamaldehyde also inhibits the quorum sensing of Pseudomonas aeruginosa (P. aeruginosa) by repressing the expression of rhlA, lasB, and pqsA (Topa et al., 2020). The mode of action of cinnamaldehyde on the bacterial cell may be mediated via membrane depolarization (Topa et al., 2018), where its hydrophobicity property facilitates bacterial cell entry and disturbs the lipid bilayer of the cell membrane, causing an increase in membrane permeability. The leaky cell membrane could release ions and vital molecules outside the bacterial cells, resulting in bacterial death (Jia et al., 2011). Cinnamaldehyde may also interact with the cell membrane and cause rapid inhibition of energy metabolism (Friedman, 2017).
The design and synthesis of efficient drug delivery systems are necessary for medicinal and pharmaceutical applications (Gopi and Amalraj, 2016). Materials development using nanotechnology has synergistically stimulated the progress of drug delivery. Many polymers have been studied in designing nano-drug delivery systems (Gopi and Amalraj, 2016). Electrospinning is a simple and versatile technique that applies electrical forces to fabricate fibers with diameters ranging from two nanometers to several micrometers using natural and synthetic polymers (Ahn et al., 2006; Bhardwaj and Kundu, 2010). Electrospun nanofibers have numerous biomedical applications, such as filtration, drug and gene delivery, wound dressings, enzyme immobilization, sensors, and catalysts (Bhardwaj and Kundu, 2010; Thenmozhi et al., 2017). Nanofibers were utilized extensively in the delivery of various drugs, including antibiotics, anticancer drugs, cardiovascular drugs, nonsteroidal anti-inflammatory drugs, anti-histamines, gastrointestinal drugs, and contraceptives (Shahriar et al., 2019). Compared with other Nano-technological techniques, electrospinning of nanofibers provides a high level of drug loading capacity and encapsulation efficiency, with a f
The used materials and their rate of degradation are two crucial factors in the fabrication of electrospun nanofibers (Dias et al., 2022). In addition, various pharmacists and researchers consider nanofibers necessary due to their advantages, such as easy functionalization, small diameters (nano/micro-sized fiber), high surface-to-volume, high porosity, flexible control, and relatively inexpensive (Dias et al., 2022).
One of the most commonly used synthetic polymers in medical and industrial fields is polycaprolactone (PCL) due to its attractive properties such as biocompatibility, biodegradability, structural stability, mechanical strength, cost efficiency, and the approval of the United States Food and Drug Administration (USFDA) for its use in human (Dias et al., 2022). However, its hydrophobic nature can lead to a very slow rate of degradation ranging from 2 to 4 years, which has limited its application in the biomedical fields (Dias et al., 2022). Therefore, this study aimed to exhibit the inhibition of biofilm formation of a widely infectious bacterium Escherichia coli (E. coli) by using the naturally available flavonoid cinnamaldehyde-loaded polycaprolactone (PCL) nanofibers as a potential means of application in the biomedical field.