Abstract
Stable and (bio)-compatible nanofibrous matrices showing effective incorporation and release of nonsteroidal anti-inflammatory drugs (NSAIDs) hold a huge potential in tissue regeneration and wound healing. Herein, a two-step, water-based and needleless electrospinning method is used to fabricate thermally cross-linked multifunctional nanofibrous substrates from a hydrophilic cellulose derivative, i.e. carboxymethyl cellulose (CMC), and polyethylene glycol (PEG) with an in situ incorporated NSAID, diclofenac (DCF). Electrospun bi-component blend nanofibers, strongly linked together by ester bonds, with different degrees of cross-linking density are achieved by varying the concentrations of butanetetracarboxylic acid (BTCA, a green polycarboxylic cross-linker) and the sodium hypophosphite (SHP) catalyst, and the temperature. The results demonstrated that not only the dimensional stability and swelling properties could be better controlled but also the morphology, fiber diameter, surface area, pore volume, pore size, and functionality of the cross-linked nanofibers. Release kinetics of DCF from the nanofibrous substrates are controlled and prolonged up to 48 h, and the overall released mass of DCF decreased linearly with increasing cross-linking degree of BTCA and SHP. Fitting of release data using various kinetic models revealed that the release of DCF follows a non-Fickian (diffusion and erosion controlled) to Fickian mechanism (only diffusion-controlled process). Cell viability testing based on crystal violet dyeing showed that the DCF-incorporating nanofibers have excellent biocompatibility and no toxic effect on human skin fibroblast cells. Overall, the reported DCF-incorporating nanofibrous substrate demonstrates high potential to be used as a smart drug delivery system in wound healing, especially due to its noninvasive characteristics.
Highlights
Nano bers of polymeric materials have been in focus for several years because of their unique morphology and internal architecture
Even though stable nano bers blends can be made from hydrophobic or mixture of hydrophobic and hydrophilic polymers (e.g., poly(lactic-co-glycolic acid) (PLGA)/polyethylene glycol (PEG),[21] etc.), they are not suitable for incorporation and release of water soluble drug such as diclofenac (DCF), the nonsteroidal anti-in ammatory drug (NSAID), which is o en used for the treatments of pain and in ammatory diseases.[22]
While the carboxymethyl cellulose (CMC)/PEG based hydrogels have been used for drug delivery and wound dressing/healing applications,[28,29] the systematic and detailed studies on electrospun nano bers from the same polymers for the release of DCF and growth of human skin cells such as broblast are very few
Summary
Nano bers of polymeric materials have been in focus for several years because of their unique morphology and internal architecture. CMC alone provide challenges in electrospinning, which can be overcome by incorporation of hydrophilic, non-immunogenic, and non-toxic spinning agent such as PEG. The latter provides adequate chain entanglement in the liquid state, and resulting in uniform ber formation. While the CMC/PEG based hydrogels have been used for drug delivery and wound dressing/healing applications,[28,29] the systematic and detailed studies on electrospun nano bers from the same polymers for the release of DCF and growth of human skin cells such as broblast are very few. No studies can be found on the thermal crosslinking and stabilization of CMC/PEG nano bers with BTCA through a sustainable, greener and two-steps approach
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