Middle ear inflammation, also known as otitis media (OM), is a condition that affects the middle ear, which is part of the ear located behind the eardrum and can be caused by viruses and bacteria [1,2]. An inflammation occurs behind the eardrum (tympanic membrane) due to the presence of various viruses, bacteria, or fungi, and severe pus (fluid) is stimulated and trapped in the middle ear, such as vertigo, dizziness, fever, pain, and even inevitable permanent hearing loss problems [1,2]. The current treatment of OM, conventional ear drops, involves applying several antibiotics directly into the affected area [3,4]. However, since local delivery of antibiotics at a high level can potentially be toxic or result in antibiotic resistance, a change in the dosage of antibiotics in the affected area is necessary to eliminate these treatment-related side effects [[5], [6], [7]]. As a result, it is critical to solve this problem with a novel treatment strategy to achieve a therapeutic drug concentration in the middle ear, which is critical for efficient otic delivery. Over the last few decades, nanotechnology discovery has aroused significant interest in developing innovative drug delivery systems (DDSs) [8].

Over the last few decades, nanotechnology discovery has aroused significant interest in developing innovative drug delivery systems (DDSs) [8]. Electrospinning, which utilizes electrostatic voltage for the creation of nanofibers, can be highly effective for fabricating different types of dressings at a nanoscale. Antimicrobial dressings have been developed recently for DDSs [9]. In other words, the electrospinning method allows the production of different structures such as nanoparticles, nanofibers, nanospheres, or nanotubes to be applied in DDSs via regulating the medication supply from hydrophilic and biodegradable polymers [[10], [11], [12]]. This method has a lot of advantages, such as cost-effectiveness, ease of usage, simplicity, and reproducibility [13]. Moreover, ultra-fine electrospun fibers range in diameter from several micrometers to a few nanometers [14].

Various natural and synthetic materials have been employed to create fibrous scaffolds using electrospinning. Ethyl cellulose (EC) is an excellent biocompatible and water-insoluble polymer used primarily for slow drug release profiles [15,16]. Because of its low cost and electrospinnability, using EC in the electrospinning technique is highly preferred in drug release [17]. PHB is one of the most well-studied homopolymers in the polyhydroxyalkanoate family, known for its excellent biocompatibility, biodegradability, and high mechanical strength [18,19]. However, PHB has a low hydrophilicity, low elongation at break, and a slow breakdown rate [[20], [21], [22]]. Blending PHB with other polymers can be a possible solution to overcome these drawbacks. Recently, PHB has been combined with natural polymers like cellulose to improve the mechanical and physical characteristics of the scaffold [23]. Under physiological conditions, the presence of EC can decrease PHB crystallinity and encourage its degradation [24].

Ciprofloxacin (CIP) is a widespread fluoroquinolone antibiotic used as a local or systemic treatment for infections caused by gram-negative and gram-positive bacteria [25,26]. CIP is, therefore suitable for treating middle ear infections due to its application in the local area and the safety and effectiveness of its use against bacterial infections [27,28]. Among the antibiotics used for treating middle ear infections, amoxicillin (AMX) is another efficient treatment because it is well-absorbed and effective against both gram-positive and gram-negative bacteria [[29], [30], [31]].

In this study, electrospun drug-loaded nanofibrous scaffolds using the versatile electrospinning technique were fabricated to treat middle ear infections. Ciprofloxacin and amoxicillin antibiotics were loaded into an electrospun composite fabricated from ethyl cellulose and polyhydroxybutyrate polymer to find the optimal concentrations of their desirable properties due to having a feasible strategy to provide controlled drug release to reduce side effects of antibiotics, to increase therapeutic efficacy by providing higher and more effective doses to infected areas in the middle ear, to prevent overdosage of antibiotic usage, and as well as to avoid antibiotic resistance. The use of drug-loaded scaffolds for treating middle ear infections has not been reported yet, and this study provides a new approach to the treatment of middle ear infections.