Repositioning N-Acetylcysteine (NAC): NAC-Loaded Electrospun Drug Delivery Scaffolding for Potential Neural Tissue Engineering Application

Abstract

Traumatic brain injury (TBI) presents a serious challenge for modern medicine due to the poor regenerative capabilities of the brain, complex pathophysiology, and lack of effective treatment for TBI to date. Tissue-engineered scaffolds have shown some experimental success in vivo; unfortunately, none have yielded consummate results of clinical efficacy. N-acetylcysteine has shown neuroprotective potential. To this end, we developed a N-acetylcysteine (NAC)-loaded poly(lactic-co-glycolic acid) (PLGA) electrospun system for potential neural tissue application for TBI. Scanning electron microscopy showed nanofiber diameters ranging 72–542 nm and 124–592 nm for NAC-free and NAC-loaded PLGA nanofibers, respectively. NAC loading was obtained at 28%, and drug entrapment efficacy was obtained at 84%. A biphasic NAC release pattern that featured an initial burst release (13.9%) stage and a later sustained release stage was noted, thus enabling the prolonged replenishing of NAC and drastically improving cell viability and proliferation. This was evidenced by a significantly higher cell viability and proliferation on NAC-loaded nanofibers for rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines in comparison to PLGA-only nanofibers. The increased cell viability and cell proliferation on NAC-loaded nanofiber substantiates for the repositioning of NAC as a pharmacological agent in neural tissue regeneration applications.

Electrospun Membranes as a Porous Barrier for Molecular Transport: Membrane Characterization and Release Assessment

“…The fibers produced by 5% PCL solution are narrower than those produced by 10% PCL solution. It has been well reported that the nanofibers produced by electrospinning enlarge with the increase of polymer concentration used for synthesis [ 11 , 12 , 13 ].…”

“…If the thickness, hydrophobicity and molecular interaction of fibers and transporting molecules can be a tool to impact release, would the fiber diameter and pore size be another tool to manipulate the release? It has been well reported that the fiber diameter produced by electrospinning can be reduced by decreasing the polymer concentration used for synthesis process [ 11 , 12 , 13 ]. It was also reported in microfiltration that the flux of molecules can be altered by changing the microstructure of the nanofiber membranes such as the fiber diameter and porosity [ 14 ].…”

Inhalation potential of N-Acetylcysteine loaded PLGA nanoparticles for the management of tuberculosis: In vitro lung deposition and efficacy studies

“…Surprisingly, the broadening peak of the PLGA polymer and disappearance of melting peaks instead of the intense sharp peak of the drug in the NAC-PLGA-MPPs further scrutinized that NAC was integrated into the polymer matrix; thus exists in the amorphous or partially crystalline state ( Fig. 3 D) ( Mahumane et al., 2020 ). This study also iterates the presence of the drug in a solubilized state in the lipid due to solid-state interaction induced by heating as mentioned in Fig.…”

Electrospun Porous Biobased Polymer Mats for Biomedical Applications

“…Drug-loaded electrospun neural conduits also hold great attention (Mahumane et al 2020;Haidar et al 2021;Farzamfar et al 2018). In this concept, a gabapentinloaded cellulose acetate/gelatin wet-electrospun scaffold was fabricated for neural tissue regeneration (Farzamfar et al 2018).…”

“…Improved regeneration of the created injury was achieved with the drug-loaded scaffold when compared with the gabapentin-free scaffold. N-acetylcysteine-incorporated PLGA biomimetic neuro-scaffold for traumatic brain injury was also found to be neurocompatible through ex vivo cytotoxicity assays that were realized on rat pheochromocytoma (PC12) and human glioblastoma multiform (A172) cell lines with a positive influence on cell proliferation (Mahumane et al 2020). In another study, the combined multi-technologies were used to determine the neuroprotective effects of atorvastatin and alpha-lipoic acid as active pharmaceutical ingredients in a composite scaffold.…”