Electrospun Nanofibers With pH-Responsive Coatings for Control of Release Kinetics

Abstract

Functional and stimuli-responsive nanofibers with an enhanced surface area/volume ratio provide controlled and triggered drug release with higher efficacy. In this study, chemotherapeutic agent Rose Bengal (RB) (4,5,6,7-tetrachloro-2′, 4′,5′,7′-tetraiodofluoresceindisodium)-loaded water-soluble polyvinyl alcohol (PVA) nanofibers were synthesized by using the electrospinning method. A thin layer of poly(4-vinylpyridine-co-ethylene glycol dimethacrylate) p(4VP-co-EGDMA) was deposited on the RB-loaded nanofibers (PVA-RB) via initiated chemical vapor deposition (iCVD), coating the fiber surfaces to provide controllable solubility and pH response to the nanofibers. The uncoated and [p(4VP-co-EGDMA)-PVA] coated PVA-RB nanofiber mats were studied at different pH values to analyze their degradation and drug release profiles. The coated nanofibers demonstrated high stability at neutral and basic pH values for long incubation durations of 72 h, whereas the uncoated nanofibers dissolved in <2 h. The drug release studies showed that the RB release from coated PVA-RB nanofibers was higher at neutral and basic pH values, and proportional to the pH of the solution, whereas the degradation and RB release rates from the uncoated PVA-RB nanofibers were significantly higher and did not depend on the pH of environment. Further analysis of the release kinetics using the Peppas model showed that while polymer swelling and dissolution were the dominant mechanisms for the uncoated nanofibers, for the coated nanofibers, Fickian diffusion was the dominant release mechanism. The biocompatibility and therapeutic efficiency of the coated PVA-RB nanofibers against brain cancer was investigated on glioblastoma multiforme cancer cells (U87MG). The coated PVA nanofibers were observed to be highly biocompatible, and they significantly stimulated the ROS production in cells, increasing apoptosis. These promising results confirmed the therapeutic activity of the coated PVA-RB nanofibers on brain cancer cells, and encouraged their further evaluation as drug carrier structures in brain cancer treatment.

Controlled Release Utilizing Initiated Chemical Vapor Deposited (iCVD) of Polymeric Nanolayers

“…Hydrogel layers containing 4-vinyl-pyridine (4VP) are also pH-responsive but their behavior is opposite to that of an enteric coating. The 4VP-based hydrogel layers display enhanced swelling in acidic environment, because the pyridine functional group converts to its conjugate acid form at low pH (Ghasemi-Mobarakeh et al, 2019 ; Sayin et al, 2019b ). The cationic nature of 4VP-containing polymers at low pH enhances their swelling.…”

“…Controlled drug release from textiles is of considerable practical interest for numerous applications including dressings that accelerate wound healing and for transdermal drug delivery (Ghasemi-Mobarakeh et al, 2019 ). Additionally, the encapsulation of biodegradable fiber-based substrates is desired for fabricating implantable patches utilized for site-specific drug delivery (Sayin et al, 2019b ). Fiber-based substrates have a high surface area available for drug release.…”

“…Fiber-based substrates have a high surface area available for drug release. Extremely high surface area can be achieved using nanofiber mats, such as those produced by electrospinning (Sayin et al, 2019b ).…”

“…Conformal iCVD encapsulation has been demonstrated for a variety of common fabrics including cotton and poly(ethylene terephalate) (PET) loaded with drugs (Ghasemi-Mobarakeh et al, 2019 ). Successful conformal iCVD encapsulation was also demonstrated on mats of nanofibers of different compositions including and polycaprolactone (Ghasemi-Mobarakeh et al, 2019 ), polyvinyl alcohol (Sayin et al, 2019b ), and gelatin (Mansurnezhad et al, 2020 ). Drop-casting was one method utilized to load drugs onto the fabrics (Ghasemi-Mobarakeh et al, 2019 ).…”

“…By using a low-growth temperature and by avoiding the use of solvent, the iCVD method enables polymers to form directly on fragile substrates without degrading them. Indeed, pharmaceuticals have been demonstrated to retain their efficacy after being encapsulated with iCVD layers (Sayin et al, 2019b ; Decandia et al, 2020 ).…”