International Journal of Pharmaceutics最新文献

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss, α-synuclein aggregation, mitochondrial dysfunction, and persistent neuroinflammation. Despite symptomatic advances, the blood-brain barrier (BBB) continues to restrict the delivery of many potentially disease-modifying agents. Intranasal (IN) administration, by exploiting direct olfactory and trigeminal pathways, offers a non-invasive means to bypass the BBB. When combined with lipid-based nanoparticles (LNPs), this route has shown promise in enhancing central nervous system targeting, drug protection, and controlled release. This review examines the preclinical landscape of LNP-enabled IN delivery for PD, highlighting applications across dopamine replacement, anti-aggregatory strategies, antioxidant and anti-inflammatory therapies, and neurotrophic or gene-based interventions. In animal models, IN-LNP systems have achieved significant increases in brain uptake compared to free drug, with associated improvements in behavioral metrics such as motor coordination and dopaminergic neuron survival. However, these encouraging findings are drawn almost exclusively from rodent studies; no clinical trials have yet evaluated IN-LNP platforms in human PD. Major translational challenges persist, including interspecies anatomical differences, limited long-term safety data, formulation variability, and regulatory complexity. As such, while IN-LNP strategies represent a promising and versatile approach, their clinical potential is contingent on rigorous future validation.

The potential of Adansonia digitata (baobab) pulp polysaccharides (BB), combined with whey protein (WP) and alginate (ALG), was evaluated as a novel pharmaceutical excipient to enhance the viscosity, swelling behavior, controlled release, and mucoadhesive properties of hydrogels prepared by the ionotropic gelation technique. Hydrogels based on BB, WP, and ALG, alone or in combinations (WP/BB, WP/ALG, ALG/BB, and WP/ALG/BB), were characterized by infrared spectroscopy and zeta potential measurements. Rheological, swelling, controlled release, and mucoadhesion studies were conducted to assess the functional contribution of BB and its synergistic effects with WP and ALG. All polymers exhibited viscoelastic solid behavior (G' > G″). For each polymer, with or without crosslinking, molecular interactions were observed, leading to variations in the Tan δ parameter. The crosslinked WP/ALG/BB hydrogel exhibited reduced polymer swelling and provided a more sustained release of the incorporated active substance. In vitro and ex vivo studies demonstrated strong interactions between the polymeric matrices and intestinal mucus, with the WP/ALG/BB system showing the highest mucoadhesion. Further in vivo investigations are needed to confirm the ability of BB to enhance the oral bioavailability of active substances. Overall, Adansonia digitata pulp polysaccharides, in combination with whey protein and alginate, represent a promising natural excipient for the development of bioadhesive hydrogels and cold-gelled delivery systems in pharmaceutical formulations.

Infected wounds present significant clinical challenges due to persistent bacterial infection, prolonged inflammation, impaired angiogenesis, and tenacious biofilm formation, which collectively hinder the healing process. Conventional monotherapies often fail to address these intertwined pathological factors effectively. In this study, we developed a novel hot spring-inspired microneedle (MN) patch for co-delivery of inactivated Akkermansia muciniphila (Akk), copper sulfide nanoparticles (CuS NPs), and arginine (Arg) to promote healing of infected wounds. The MN system not only penetrates biofilms physically but also delivers therapeutic agents efficiently into the wound bed. Under near-infrared laser irradiation, CuS NPs generate mild photothermal heating, mimicking the thermal component of hot spring therapy. Importantly, we discovered that Arg facilitates the degradation of CuS NPs, leading to sustained release of Cu²⁺ ions. This process combines mild photothermia with copper ion release to emulate a "hot spring-like" ion bath, providing synergistic antibacterial and pro-angiogenic effects. Meanwhile, inactivated Akk contributes to immunomodulation by polarizing macrophages toward an anti-inflammatory phenotype, thereby alleviating chronic inflammation. Together, these components work cooperatively through photothermal therapy, antibacterial action, angiogenesis promotion, and anti-inflammatory modulation, resulting in accelerated wound closure in an infected mouse model. This multifunctional MN platform represents a promising therapeutic strategy for managing chronic infected wounds.