Improving the transdermal absorption of weakly soluble drugs for topical use can help to prevent and treat skin photoaging. Nanocrystals of 18β-glycyrrhetinic acid (i.e., NGAs) prepared by high-pressure homogenization and amphiphilic chitosan (ACS) were used to form ANGA composites by electrostatic adsorption, and the optimal ratio of NGA to ACS was 10:1. Dynamic light scattering analysis and zeta potential analysis were used to evaluate the nanocomposites’ suspension, and the results showed that mean particle size was 318.8 ± 5.4 nm and the zeta potential was 30.88 ± 1.4 mV after autoclaving (121 °C, 30 min). The results of CCK-8 showed that the half-maximal inhibitory concentration (IC50) of ANGAs (71.9 μg/mL) was higher than that of NGAs (51.6 μg/mL), indicating that the cytotoxicity of ANGAs was weaker than that of NGAs at 24 h. After the composite had been prepared as a hydrogel, the vertical diffusion (Franz) cells were used to investigate skin permeability in vitro, and it was shown that the cumulative permeability of the ANGA hydrogel increased from 56.5 ± 1.4% to 75.3 ± 1.8%. The efficacy of the ANGA hydrogel against skin photoaging was studied by constructing a photoaging animal model under ultraviolet (UV) irradiation and staining. The ANGA hydrogel improved the photoaging characteristics of UV-induced mouse skin significantly, improved structural changes (e.g., breakage and clumping of collagen and elastic fibers in the dermis) significantly, and improved skin elasticity, while it inhibited the abnormal expression of matrix metalloproteinase (MMP)-1 and MMP-3 significantly, thereby reducing the damage caused by UV irradiation to the collagen-fiber structure. These results indicated that the NGAs could enhance the local penetration of GA into the skin and significantly improve the photoaging of mouse skin. The ANGA hydrogel could be used to counteract skin photoaging.

Alzheimer’s disease (AD) is a common neurodegenerative disorder with limited effective treatments. Cod skin collagen peptides (CSCPs) have neuroprotective potential for AD but face poor bioavailability—due to gastrointestinal enzyme cleavage and hepatic first-pass metabolism—prompting this study to develop a nanodelivery system to enhance CSCPs’ efficacy. Trimethyl chitosan (TMC)-based CSCP-loaded nanoparticles (CSCPs-NPs) were synthesized via ionic gelation, characterized for physicochemical properties, and tested in a D-galactose-induced AD mouse model (six groups: normal control, model, CSCPs low/high dose, blank NPs, CSCPs-NPs) using behavioral tests, histopathology, immunohistochemistry, and ELISA. CSCPs-NPs had a hydrodynamic diameter of 93.25 ± 21.52 nm, polydispersity index of 0.18 ± 0.13, 61.17% encapsulation efficiency, and sustained 24 h release. In AD mice, CSCPs-NPs significantly improved cognitive function and motor coordination, reduced hippocampal atrophy, preserved neurons, and mitigated oxidative stress, neuroinflammation, and apoptosis (upregulated Bcl-2, downregulated Bax)—effects matching high-dose free CSCPs. This TMC-based nanoformulation enhances CSCPs’ bioavailability and provides a promising strategy for AD intervention.

Excessive short-term ethanol intake often causes acute intoxication and multi-organ damage, especially to the liver and brain. Thus, developing safe and effective preparations for hangover relief, liver protection, and brain function regulation is of great practical significance. In this study, we fabricated a thermosensitive chitosan (CS)–sea cucumber peptide (SCP) hydrogel (CS–SCP gel) loaded with SCP using NaHCO₃ as a crosslinker and characterized its properties. Kunming mouse models of anti-intoxication and acute alcohol-induced liver and brain injuries were established. The anti-intoxication and organ-protective effects of the CS–SCP gel were comprehensively evaluated through behavioral observation, liver histopathology, and biochemical assays of serum and liver, kidney, and brain tissues. The CS–SCP gel exhibited a phase transition temperature of 35.7 °C, a water absorption rate of 1015.47%, and a cumulative peptide release of 74.83% within 330 min. In mice, it prolonged the latency to drunkenness; shortened alcohol-induced sleep and sobering time; reduced blood ethanol, transaminase, and lipid levels; upregulated hepatic antioxidant enzymes; downregulated pro-inflammatory cytokines, and alleviated lipid peroxidation. It also enhanced brain antioxidant capacity, suppressed cerebral inflammatory cytokines, and maintained cholinergic neurotransmitter homeostasis. Collectively, with sustained release, CS–SCP gel is expected to prolong the pharmacological action of SCP, enhance therapeutic efficacy, and protect against alcohol-induced liver and brain injury through the regulation of oxidative stress and attenuation of inflammation.