Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder characterized by immune-mediated platelet destruction, impaired thrombopoiesis and a bleeding diathesis, with growing recognition of accompanying inflammatory and immunoregulatory disturbances. Despite the widespread use of corticosteroids, intravenous immunoglobulin (IVIG) and thrombopoietin receptor agonists (TPO-RAs), 30–50% of patients exhibit incomplete, unstable or transient platelet responses, underscoring a persistent unmet need for mechanism-informed therapeutic strategies. Current management paradigms remain largely focused on platelet count restoration rather than direct modulation of pathogenic platelet–immune crosstalk. Accumulating pre-clinical evidence, supported by limited clinical observations, implicates platelet glycoprotein VI (GPVI), a collagen receptor and immunothrombotic signalling hub, as a mechanistically relevant contributor to platelet hyperactivation, inflammatory amplification and aberrant platelet–leucocyte interactions in ITP. Experimental models indicate that GPVI-dependent signalling pathways can promote thromboinflammatory responses, facilitate immune cell engagement and influence platelet clearance dynamics, positioning GPVI as a plausible, albeit incompletely validated, therapeutic target. Emerging pre-clinical studies suggest that selective modulation of GPVI signalling may attenuate pathogenic platelet activation while preserving essential haemostatic function, thereby improving platelet survival and functional competence. This review integrates current insights into GPVI biology within the broader immunopathological landscape of ITP and evaluates innovative therapeutic concepts, including GPVI-targeted inhibitors deployed through nanocarrier systems, autologous platelet-mediated delivery and hydrogel-based protective platforms designed to enhance targeting precision and durability. We further discuss the rationale for combination strategies with established therapies and the potential utility of GPVI-linked biomarkers and platelet functional profiling to guide patient stratification. By reframing platelets as active immunoregulatory effectors rather than passive autoimmune targets, this review advances a mechanistic framework for next-generation, precision-oriented intervention in ITP. Although clinical validation remains limited, GPVI-centred strategies represent a rational and testable avenue for moving beyond symptomatic platelet augmentation towards disease-modifying immunothrombotic modulation.

Cutaneous leishmaniasis (CL) is a major health problem in many countries and its current treatment involves multiple parenteral injections with toxic drugs and requires intensive health services. Previously, the efficacy of a single subcutaneous injection with a slow-release formulation consisting of poly(lactide-co-glycolide) (PLGA) microparticles loaded with an antileishmanial 3-nitro-2-hydroxy-4,6-dimethoxychalcone (CH8) was demonstrated in mice model. In the search for more easily synthesized active chalcone derivatives, and improved microparticle loading, CH8 analogues were synthesized and tested for antileishmanial activity in vitro and in vivo. The 3-nitro-2′,4′,6′-trimethoxychalcone (NAT22) analogue was chosen for its higher selectivity against intracellular amastigotes (selectivity index = 1489, as compared with 317 for CH8) and more efficient synthesis (89% yield, as compared with 18% for CH8). NAT22 was loaded into PLGA / polyvinylpyrrolidone (PVP) polymeric blend microspheres (NAT22-PLGAk) with average diameter of 1.9 μm. Although NAT22-PLGAk showed similar activity to free NAT22 in killing intracellular parasites in vitro (IC50 ~ 0.2 μm), in vivo studies in Leishmania amazonensis – infected mice demonstrated the significant superior efficacy of NAT22-PLGAk to reduce the parasite load. A single intralesional injection with NAT22-PLGAk was more effective than eight injections with free NAT22. Together, these results show that NAT22-PLGAk is a promising alternative for single-dose localized treatment of CL.