Fabrication of Electrospun Mucoadhesive Membranes for Therapeutic Applications in Oral Medicine

Abstract

Oral mucosal lesions are related to several etiologies, including trauma, infection, and immunologic and neoplastic diseases. Their prevalence varies greatly depending on ethnicity, gender, and exposure to risk factors. Currently, most oral mucosal lesions are treated with creams, mouthwashes, or gels containing suitable drugs. However, topical medications may be relatively ineffective as they are removed rapidly from oral surfaces, limiting drug contact times. Systemic medications might be more effective but are associated with unacceptable off-target side effects. The aim of this study was to produce novel polymeric mucoadhesive membranes for therapeutic applications on the oral mucosa using electrospinning. Poly(vinylpyrrolidone) (PVP) and Eudragit RS100 (RS100) were used for the fabrication of membranes, whereas dextran (Dex) or poly(ethylene oxide) (PEO) particles were incorporated to enhance their mucoadhesive properties. An electrospun poly(caprolactone) (PCL) backing layer (BL) was added to create a dual-layer system. Solution properties were studied using rheometry, and membranes were characterized using differential thermal analysis and scanning electron microscopy. Solubility, surface hydrophobicity, and adhesion properties were also investigated. The solution viscosity varied depending on the composition and concentration, affecting fiber production. The addition of RS100 to PVP resulted in reduced membrane porosity and solubility, and increased surface hydrophobicity and in vitro adhesion times. Dex and PEO particles were located on the surface of the fibers. A PCL BL was successfully produced, with enhanced attachment between layers achieved through thermal treatment. PVP homopolymer membranes did not adhere to plastic or porcine mucosa, whereas PVP/RS100 membranes with and without PEO or Dex were tightly adherent. In conclusion, PVP and RS100 may be combined to tailor membrane properties. Furthermore, electrospinning facilitated the production of membranes consisting of mucoadhesive-fabricated fibers displaying increased surface area and long-lasting adhesive properties. These novel compositions exhibit great potential for the fabrication of mucoadhesive patches for therapeutic applications in oral medicine.

Eudragit E100/poly(ethylene oxide) electrospun fibers for DNA removal from aqueous solution

“…The Evonik—Eudragit products (L, S, E, and FS series) are copolymers of esters of acrylic and methacrylic acid with well‐defined pH‐dependent behavior, being soluble in digestive fluids at specific pH (depending on specific alkaline or acidic functional groups on copolymers) . In addition to the conventional use as granules, powders, and aqueous solutions, Eudragit copolymers have been applied as support for electrospinning procedure .…”

“…The improvement in the chemical properties of Eudragit‐based electrospun fibers is typically provided by incorporation of polymeric additives. Santocildes et al . associated Eudragit derivatives and polyvinylpyrrolidone for oral treatment of mucositis.…”

Mucoadhesive Electrospun Fibre-Based Technologies for Oral Medicine

“…Electrospinning uses a high voltage (5–30 kV) to produce polymer fibres, with diameters ranging from two nanometres up to several micrometres from a polymer solution or melt [ 22 ]. So far, at least 12 electrospun medical devices are in late stages of regulatory or market approval, with the majority being used as surgical grafts or for tissue regeneration [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. The technique is particularly promising for drug delivery because of its versatility and the high surface area of the resulting nanofibre mesh, which allows an active compound to be incorporated and released at a controlled rate by either diffusion or degradation of the nanofibres [ 3 ].…”

“…These polymers are charged at physiological pH; therefore, electrostatic interactions in combination with hydrogen bonding are likely involved in the adhesion mechanism. Synthetic polyionic polymers such as poly(acrylic acids), including Carbopol ® [ 66 ], and the Evonik Eudragit ® series have also shown mucoadhesive properties [ 34 , 67 ]. Thiolated polymers, such as thiolated chitosan [ 68 ] and thiolated hyaluronic acid [ 69 ], adhere by forming disulfide bridges with cysteine domains in mucins, resulting in adhesion through chemical adsorption.…”

“…The most common tests involve use of a texture analyser to measure mucoadhesive strength, the perpendicular force required to break, pull or peel away the sample from a model membrane [ 70 , 71 , 72 ]. Alternatively, in vitro residence time tests may be used to measure time until detachment, for example from ex vivo animal mucosa in a simulated saliva medium [ 34 ].…”