*4.2. Sublingual/Buccal*

The oral mucosa has its own subdivisions according to its different regions, namely, buccal, sublingual and gingival. A few years ago, researchers were also interested in designing nanofiber based drug delivery systems for sublingual (under the tongue) or buccal (between the gums and teeth) routes of administration. The sublingual or buccal delivery systems usually allow the drug-loaded electrospun nanofibers to dissolve in the presence of mucus so that the drug can directly penetrate into the small blood vessels. Interestingly, these oromucosal routes of administration are the most studied sites for nanofiber-based therapeutics, offering versatile and multifunctional drugs, DNA, RNA, protein, peptide, growth factors or vaccine delivery platforms [51].

#### *4.3. Rectal*

Pediatric patients (aged under 6 months) usually cannot swallow any drug or food supplement. Under such circumstances, the rectal route could be the best alternative to oral drug delivery systems. In addition, the rectal route is also effective in cases of unconscious or vomiting patients. An electrospun nanofiber-based rectal drug delivery system is continually gaining popularity. In the treatment of post-operative peritoneal effusion following rectal/pelvic surgery, electrospun nanofibers could be considered a safe potential biocompatible, and biodegradable sealing fiber. The first clinical trial on the safety and sealing properties of electrospun nanofibers in lymphorrhea following pelvic surgery was published in 2014 [52]. The authors used a synthetic material (PuraMatrix) that consists of sixteen amino acid peptides to fabricate self-assembled nanofibers. A total of 20 colorectal cancer patients participated in the clinical trial. After a 2–3 month follow-up period, a significant reduction in post-operative drainage volumes was apparent in the experimental group compared with the control group. In another study, Modgill and co-workers investigated the permeability of penicillin from an extremely thin nanofiber scaffold through different biological membranes. The authors used PVA to fabricate ciprofloxacin-loaded ultra-thin nanofibers. In vitro permeability studies exhibited the potency of electrospun nanofibers compared with the plain drug. The PVA nanofibers revealed the highest ciprofloxacin permeability in the rectal mucosal membrane. The drug release study showed the controlled release behavior of ciprofloxacin from nanofibers in the rectal mucosal membrane, whereas the control group showed a high degree of fluctuations [53].

#### *4.4. Vaginal*

Electrospun nanofiber scaffolds targeting vaginal routes have recently been investigated. However, the acidic condition of vaginal mucosa (~pH 4) should be considered before designing vaginal drug delivery systems using nanofibers. For example, Brako et al. fabricated progesterone-encapsulated nanofibers targeting the vaginal route of administration. The authors used a mucoadhesive molecule (carboxymethylcellulose) for the fabrication of electrospun nanofibers. As-synthesized progesterone/carboxymethylcellulose electrospun nanofibers exhibited sustained release properties [54,55]. Another example of nanofiber-based vaginal drug delivery would be a study involving the anti-HIV drug (maraviroc), in which the authors spun maraviroc either with PVP or PEO and demonstrated fast drug dissolving properties upon contact with moisture [56].
