Microfibers and nanofibers are solid polymer-based carriers that exhibit particle sizes ranging from micrometers to nanometers, respectively, in at least one dimension. In Fig. 1, examples of nanofibers along with their representative particle size distribution are presented [1]. These fibers have gained significant attention in various fields due to their unique properties and potential applications. They are commonly fabricated using the electrospinning technique. Other techniques such as template synthesis, phase separation, drawing, and self-assembly have also been used for microfibers and nanofibers preparation, but their application has been limited due to their long and time-consuming process and difficulties in large-scale production [2]. Various electrospinning techniques, including blend electrospinning, melt electrospinning, co-axial electrospinning, emulsion electrospinning, and gas jet electrospinning [3] have been considered for fabricating ultrafine nanofibers and microfibers from natural, synthetic, or hybrid polymers [4]. As shown in Fig. 2, the electrospinning technique requires the application of high-voltage electrostatic forces along with suitable temperature, humidity, and flow rate conditions to transform polymer solutions into nanofibers and microfibers [5]. The electrospinning technique, also known as electrostatic spinning, can be performed through either the uni-axial (single-needle) or co-axial approaches. In this regard, an electrical field is required to push the polymer solution through a narrow viscoelastic jet to reduce the diameter of the polymers in ranges of micrometer and nanometer for the preparation of microfibers and nanofibers, respectively. The co-axial electrospinning technique is commonly used to fabricate core-sheath nanofibers. Therefore, as shown in Fig. 2, each electrospinning device is composed of three main parts of high-voltage supplier, the capillary tube that act as a polymer reservoir with an ending narrow needle, and a collector [6]. To prepare core-shell microfibers and nanofibers, two distinct polymer solutions are required, with the inner solution (core part) surrounded by the outer solution (shell part), therefore at least two co-flowing phases are required for the preparation of core-sheath nanofibers and microfibers [7,8]. A schematic view of various electrospinning techniques used in microfiber and nanofiber preparation is shown in Fig. 3. Various small molecules and active ingredients can be incorporated into the core or shell part of these microfibers and/or nanofibers for targeted drug delivery purposes, allowing for controlled and sequential drug release [9]. Furthermore, microfibers and nanofibers have emerging applications in tissue engineering and tissue regeneration [10].

Nano and microfibers can be fabricated from a variety of natural, synthetic, or hybrid polymers. Natural polymers commonly used in electrospinning include chitosan, cellulose derivatives, chitin, dextran, starch, hyaluronic acid, alginate, and collagen. Synthetic polymers and copolymers such as poly (lactic-co-glycolic acid) (PLGA) [11], poly (ε-caprolactone-co-lactide) (PCLA), poly (ε-caprolactone) (PCL), poly (lactic acid) (PLA), poly (ethylene glycol) (PEG), and poly (ethylene oxide) (PEO) are also widely employed in nano and microfiber fabrication [4]. Natural polymeric nanofibers are particularly promising due to their biocompatibility and biodegradability [12]. Chitin and chitosan, for example, are frequently used polysaccharides in tissue engineering applications due to their scaffolds' similarity to the extracellular matrix [13]. Additionally, chitosan exhibits anticancer activities, making it suitable for targeted drug delivery in various neoplastic disorders [4]. Synthetic polymer nanofibers, especially those with biodegradability, have emerged as important materials in tissue engineering and drug delivery. The blending of polymers can significantly impact the release profile of encapsulated drugs [14]. Hybrid composite nanofibers, which combine natural and synthetic polymers to achieve enhanced physicochemical properties, are highly desirable for targeted drug delivery and tissue engineering purposes. Synthetic polymers can provide a sturdy backbone, while natural polymers promote cellular attachment [4,13].

Nanofibers and microfibers offer several advantages as drug delivery systems. These include [4,15,16]:

Biodegradability: Nanofibers and microfibers made from natural or biodegradable synthetic polymers can be designed to degrade over time, ensuring the safe elimination of the carrier material from the body.

Physicochemical stability: The structure of nanofibers and microfibers provides stability to the encapsulated drugs, protecting them from degradation and maintaining their integrity during storage and transport.

Ease of production: Electrospinning and other fabrication techniques allow for the relatively simple and scalable production of nanofibers and microfibers, making them suitable for large-scale manufacturing.

High drug loading and entrapment efficiency: These fiber-based systems have a large surface area-to-volume ratio, enabling high drug loading and efficient encapsulation of active ingredients.

Stimuli-responsive drug delivery: Nanofibers can be engineered to respond to specific stimuli such as pH, temperature, or enzymatic activity, enabling controlled and triggered drug release at the desired site.

Smart cargo release potential: By incorporating stimuli-responsive materials or systems, nanofibers and microfibers can be designed to release drugs in a controlled manner, responding to specific physiological conditions or external triggers.

Simultaneous dual drug delivery: Multiple drugs or active ingredients can be loaded into the same nanofiber or microfiber system, allowing for the simultaneous delivery of different therapeutic agents, which can be beneficial for combination therapy.

Versatile incorporation of active ingredients: Nanofibers and microfibers can accommodate various types of active ingredients, including antibiotics, anticancer agents, proteins, DNAs, and RNAs, offering versatility in drug delivery applications.

Diverse release patterns: Depending on the design and composition of the nanofibers, drug release profiles can be tailored to achieve burst release, pulsatile release, delayed release, sustained release, or biphasic release patterns.

Mechanism of drug release: While diffusion is the most common mechanism of drug release from nanofibers, the choice of polymer and its physicochemical properties can also promote drug release through polymer degradation.

Enhanced drug permeation: Preparation of self-emulsifying nanofibers, which are spontaneously fabricated through the polymer contact with body fluids, can be accompanied by enhanced permeation of the encapsulated drug [16].

These advantages make nanofibers and microfibers attractive candidates for drug delivery, offering controlled and sustained release of therapeutics with the potential for improved treatment outcomes.

Nanofibers and microfibers can be utilized as drug delivery systems through different administration routes, including topical, oral, parenteral, and trans-mucosal routes. However, this review primarily focuses on their capabilities as oral drug delivery systems. The use of nanofibers and microfibers in oral drug delivery offers several advantages, such as protection of the cargo against harsh environmental conditions, and the ability to induce smart and modified drug release patterns.

The review starts with an introduction to nanofibers and microfibers, highlighting their relevance in targeted oral delivery. The subsequent sections delve into the specific applications of these fibers as oral drug delivery systems, considering their natural and synthetic polymeric origins. The detailed discussions cover various merits of nanofibers and microfibers in oral delivery, including fast disintegration, rapid dissolution, improved drug dissolution rate, enhanced oral bioavailability, controlled delivery, and stimuli-responsive drug release. The summarized information is presented in a tabular format for easy reference.