Adaptive Liver-Targeted Drug Delivery in Hepatic Disease and Impairment

Pharmacodynamics and pharmacokinetics of many therapeutic agents are altered in hepatic diseases and hepatic impairment. The liver is an important organ for drug metabolism and biotransformation; impaired hepatic function can reduce drug clearance, prolong systemic drug exposure, and increase toxicity. Some comorbidities, such as chronic kidney disease, diabetes mellitus, cardiovascular disorders, obesity, cancer, and chronic inflammatory diseases, further complicate drug metabolism and therapeutic response. Administered drug doses should be determined through a personalized therapeutic strategy in accordance with the patient’s physiological function, disease progression, and treatment response. Drug delivery systems that target the liver or respond to hepatic disease features may improve therapeutic precision while limiting systemic exposure and toxicity.Patients with hepatic dysfunction show numerous changes in drug disposition. Increased bioavailability can occur through reduced hepatic blood flow and diminished activity of hepatic enzymes, mostly cytochrome P450 isozymes, which slow drug metabolism and prolong systemic exposure. Hypoalbuminemia can increase toxicity through an enhanced free fraction of highly protein-bound drugs. Drugs may accumulate because of impaired biliary excretion in cholestasis. Moreover, when multiple diseases coexist with hepatic impairment, therapy is further complicated by altered pharmacokinetics, drug–drug interactions, and pharmacogenetic profiles. As a result, standard doses may fail to provide optimum treatment.For these reasons, there is a need for delivery systems that selectively target hepatic tissues and cells, respond to disease-specific hepatic microenvironments, or provide controlled drug exposure. This Research Topic aims to maximize therapeutic efficacy and minimize adverse drug reactions through liver-targeted, hepatic-responsive, and controlled drug-delivery systems designed for hepatic diseases and impaired hepatic function. We seek contributions focusing on different liver-targeted and hepatic-responsive drug-delivery technologies that enable the development of adaptive systems that respond to hepatic physiological and pathological changes.We welcome original research, reviews, and translational studies on the design, characterization, biological evaluation, and clinical translation of liver-targeted, hepatic-responsive, and controlled drug-delivery systems for hepatic diseases and hepatic impairment. Subthemes of interest include, but are not limited to:- Nanoparticle-based delivery systems to increase liver-targeted drug delivery, improve bioavailability, and reduce toxicity, including liposomes, solid lipid nanoparticles, dendrimers, polymeric nanoparticles, and nanocapsules that can deliver drugs selectively to diseased hepatic tissue and cells, minimizing exposure in healthy organs.- Stimuli-responsive delivery systems that release drugs in response to specific stimuli, such as altered pH, enzyme activity, temperature, oxidative stress, and inflammatory agents, to provide drug release in diseased liver tissues and reduce off-target effects.- Controlled-release formulations that maintain plasma drug concentrations for specified periods to reduce dosing frequency and minimize toxicity in patients with hepatic metabolism impairment.- Biomaterial-based carriers, namely biodegradable materials, hydrogels, and injectable depots, that enable sustained local or hepatic-directed drug release to improve patient outcomes.- Studies assessing dose-response relationships, pharmacokinetics/pharmacodynamics, safety, and therapeutic performance of liver-targeted or hepatic-responsive delivery systems in hepatic disease or impairment. Topic editors: Dr. Sibani Sarkar, Tanaya Chatterjee, Taha Koray Sahin Source: https://www.frontiersin.org/research-topics/84464/adaptive-liver-targeted-drug-delivery-in-hepatic-disease-and-impairment