Beyond the Bilayer: Polymeric and Particulate Nanocarriers for Barrier-Crossing, Target-Specific Drug Discovery

Reaching a molecular target is often less about the drug than about getting the drug to where the target is. The body’s biological barriers — the blood–brain barrier, the dense and disorganized tumor microenvironment, the stratum corneum, and mucosal surfaces — turn many promising leads into pharmacological non-starters. Non-vesicular nanocarriers offer a distinct route through: polymeric nanoparticles, protein- and albumin-based systems, dendrimers, nanocrystals, and inorganic particulate platforms can be engineered to survive transit, cross a defined barrier, and release a chemically defined compound at its site of action, changing the pharmacology that follows.This Research Topic focuses on that chain of events — from a rationally engineered solid or polymeric nanoparticle, across a biological barrier, to a measurable interaction between the delivered lead and its target. The emphasis is on the pharmacology of the delivered compound rather than the carrier alone: how nanoparticle delivery alters target engagement, potency, selectivity, exposure at the target site, and the downstream physiological response. We are equally interested in the medicinal-chemistry side — lead optimization and structure–activity of chemically defined bioactive and natural-product-derived molecules whose pharmacology only becomes tractable once a nanoparticle solves the delivery problem.We invite Original Research, Reviews, Mini Reviews, Methods, Brief Research Reports, and Hypothesis and Theory articles addressing, but not limited to:Polymeric, protein/albumin, dendrimeric, nanocrystal, and inorganic nanoparticle platforms engineered for target-site deliveryBarrier-crossing pharmacology: blood–brain barrier, tumour microenvironment, transdermal, and mucosal routes, with target engagement demonstrated at the destinationTarget identification, mechanism of action, and structure–activity of the delivered lead (small molecules and biopharmaceuticals)Medicinal-chemistry lead optimization of chemically defined bioactive and purified natural-product molecules formulated in nanoparticlesQuality-by-design formulation explicitly linked to pharmacodynamic and dose–response outcomesPharmacokinetics, biodistribution, metabolism, and toxicology comparing free versus nanoparticle-delivered agentsPreclinical efficacy in disease models with mechanistic, target-focused readoutsScope notes for authors. This Research Topic is dedicated to non-vesicular, solid and polymeric particulate nanocarriers and to the barrier-crossing pharmacology of the leads they deliver. In keeping with the section, all delivered agents must be chemically defined, with structure and purity established by appropriate analytical methods (e.g. chromatography and/or mass spectrometry); studies on crude extracts or multiherbal preparations are outside scope. In-silico-only work and clinical/patient-outcome studies without an experimental pharmacology component are excluded. Anti-cancer submissions must include a minimum of two in vitro cell lines. Every contribution should provide in-depth insight into the interaction between the delivered drug and its biological target and the pharmacological consequences of that interaction. This collection supports SDG 3: Good Health and Well-being. Topic editors: Shaheen Sultana, Priyanka Kriplani, Akhlesh Kumar Jain Source: https://www.frontiersin.org/research-topics/85070/beyond-the-bilayer-polymeric-and-particulate-nanocarriers-for-barrier-crossing-target-specific-drug-discovery