Recent Advances in the Formulation and in-Vitro Evaluation of N-Acetylcysteine Drug Delivery Systems

N-acetylcysteine (NAC) is a cysteine-derived compound with antioxidant, mucolytic and anti-inflammatory properties and established clinical use in selected toxicological and respiratory settings. Its broad biological activity has encouraged investigation of NAC in localized and advanced drug-delivery systems intended to improve stability, residence time, release control and delivery to difficult biological targets. This review summarizes formulation and in-vitro evaluation approaches described in the supplied literature, with emphasis on polymeric and lipid nanoparticles, magnetic nanoparticles, conventional hydrogels, thermo-responsive hydrogels and multifunctional NAC systems. NAC-loaded lipid nanoparticles functionalized with D-amino acids were reported to have a mean hydrodynamic size of approximately 200 nm and demonstrated activity against Pseudomonas aeruginosa biofilms with low cytotoxicity and low hemolytic activity in the reported models. NAC-loaded sodium alginate–guar gum hydrogel showed an optimized formulation with a pH of 6.2 ± 0.168 and density of 1.026 ± 0.21, together with antimicrobial, antioxidant and cell-supporting potential. A methylcellulose-based thermo-responsive hydrogel demonstrated temperature-dependent gel formation and favorable fibroblast responses at lower tested NAC concentrations. The NAC–resveratrol–cyclodextrin multicomposite NACESOL™ showed greater reported biofilm reduction than free NAC at selected concentrations. Polymeric PLGA nanoparticles have additionally been investigated for pulmonary delivery, while poly-L-lysine-coated magnetic nanoparticles provide a route for MRI-assisted monitoring of NAC distribution and release. Across these systems, evaluation commonly includes particle size, polydispersity, zeta potential, drug content, encapsulation efficiency, spectroscopic and thermal characterization, morphology, release testing, stability, antioxidant activity, antimicrobial or antibiofilm assays and cell-compatibility studies. Because experimental conditions vary substantially between studies, release percentages and biological outcomes should not be compared without considering the formulation and assay conditions. Overall, the reviewed evidence supports continued development of NAC delivery platforms, while standardized testing and further in-vivo validation remain important.