In the present study, novel conjugated lignin/chitosan nanoparticles (LCNPs) were synthesized by a first-time simple green methodology using interfacial co-assembly between both biopolymers. The physicochemical (ζ-potential, size, concentration of surface acidic/basic groups), structural (surface functional groups), and morphological characteristics of the blank and quercetin-encapsulated (Q-LCNPs) nanoparticles were analyzed by the Boehm method, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), and X-ray diffraction (XRD). The experimentally determined encapsulation capacity was satisfactory—95.75%. The in vitro quercetin release efficiency in acidic solution that simulated the gastric microenvironment was 21.9%, followed by 68.5% and 99.8% cumulative release efficiency in simulated intestinal media at pH 7.4 and 6.8, respectively. The satisfactory applicability of the Weibull and sigmoidal mathematical models towards the experimental in vitro release data was indicative of the remarkable roles of diffusion and relaxation mechanisms.

Background/Objectives: The aim of the present study was to conduct a systematic in vitro assessment of the biofunctionalities of newly synthesized lignin (LNPs) and lignin–chitosan nanoparticles (LCNPs) via a comparative in vitro estimation of their cytotoxicity, cytocompatability potential, radical-scavenging activity, and antimicrobial performance, thereby establishing a benchmark for their sustainable design and biomedical applications. Methods: LNPs and LCNPs were synthesized via “green” self-assembly and co-assembly methods. Results: In vitro cytotoxicity studies on L929 fibroblasts and HaCaT keratinocytes demonstrated higher long-term viability for LCNPs (half-maximal inhibitory concentration IC₅₀ = 3.05 mg/mL at 72 h) compared with LNPs (IC₅₀ = 1.37 mg/mL), while both formulations maintained >76% viability at a concentration of 0.5 mg/mL. Electron Paramagnetic Resonance (EPR) and spectrophotometric antioxidant assays displayed strong radical scavenging activity, with LNPs excelling in ^●OH, NO, and ABTS scavenging and LCNPs exhibiting enhanced lipid peroxidation and superoxide inhibition potential. Antimicrobial testing revealed minimal inhibitory concentration (MIC) reductions of the nanoparticles up to 8–13-fold compared to lignin solutions, with LCNPs showing higher activity against Gram-positive and Gram-negative microbial strains. Conclusions: These results highlight LCNPs as biocompatible, antioxidant, and antimicrobial nanoplatforms with potential for regenerative medicine, oxidative stress mitigation, and infection control.

Background/Objectives: Acetaminophen (paracetamol or APAP) overdose is a major cause of acute liver injury mediated by oxidative stress, inflammation, and hepatocellular necrosis. The present study investigates the in vivo hepatoprotective potential of morin (M), lignin nanoparticles (LN), and morin-encapsulated lignin nanoparticles (LMN) against APAP-induced hepatotoxicity in mice. The specific goal was to determine whether LMN could strengthen hepatic antioxidant and anti-inflammatory defenses prior to toxic insult, which aligns with a prophylactic model rather than a post-injury clinical rescue approach. This study was guided by the primary hypothesis that LMN pretreatment would markedly reduce APAP-induced hepatic injury. Methods: Experimental groups included control, APAP, M, LN, LMN, M+APAP, LN+APAP, and LMN+APAP treatments. Serum hepatic biomarkers, oxidative stress parameters, and inflammatory cytokines were analyzed to assess protective responses. Results: APAP exposure markedly elevated aspartate aminotransferase (AST) and alkaline phosphatase (ALP) levels, indicating severe hepatic dysfunction, accompanied by increased lipid peroxidation and pro-inflammatory cytokine production. LMN+APAP treatment significantly restored hepatic enzyme levels to approximately normal values and suppressed malondialdehyde (MDA) formation, while enhancing superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. LMN also downregulated interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interleukin 1β (IL-1β), while upregulating interleukin 10 (IL-10), suggesting effective attenuation of inflammatory signaling. Correlation analyses demonstrated positive interactions between MDA, cytokines, and hepatic enzymes, whereas antioxidant enzyme levels were inversely correlated with liver injury markers. Histopathological analysis revealed that treatment with LMN enhanced hepatoprotection, demonstrating predominantly mild, reversible lesions and suggesting a synergistic antioxidant and immunomodulatory effect. Conclusions: It could be concluded that LMN provided superior hepatoprotection compared to M or LN. These findings establish LMN as a promising bio-based nanotherapeutic agent for mitigating drug-induced hepatotoxicity through coordinated antioxidant and anti-inflammatory mechanisms.