Multi-Endogenous Nanoformulation for Endocannabinoid and Hormonal Modulation of Key Signaling Pathways in Resistant Hypertension.

Despite notable advances in the development of synthetic antihypertensive therapies, resistant hypertension remains a complex and challenging condition. Its persistence is attributed to multifactorial resistance mechanisms involving several key signaling pathways, including Hsp70, WT1, AT1, and iNOS. A promising therapeutic strategy involves the simultaneous modulation of these pathways using endogenous bioactive compounds delivered via controlled and sustained-release nanosystems. Such nanoformulations enable the co-delivery of multiple agents, enhancing their bioavailability, stability, and therapeutic precision. This multifaceted approach allows for more effective modulation of the underlying pathophysiological processes of hypertension, including inflammation, oxidative stress, and vascular dysfunction. By integrating these compounds into a single delivery platform, nanoformulations may offer a significant advancement in the treatment of resistant hypertension and related cardiovascular disorders. Future research should prioritize the optimization of these delivery systems and the assessment of their efficacy in clinically relevant models.