Objective: This research intends to develop an innovative co-delivery method for an angiotensin II receptor blocker (ARB) and a potent antioxidant. The main goal is to create a single, optimised formulation that delivers both therapies simultaneously, similar to a liposome or nanoparticle. By preventing angiotensin II's hypertensive effects and reducing related oxidative stress, this approach aims to increase synergistic efficacy. The objective is to provide a more complete treatment for hypertension by achieving better blood pressure control, better vascular protection, and possible regression of end-organ damage when compared to traditional monotherapies.Design and method: Lipid-polymer hybrid nanoparticles will be used in the system. The polymeric core will include the ARB (such as losartan), while the lipid shell will contain the antioxidant (such as resveratrol). For synergistic antihypertensive and antioxidant benefits, this architecture guarantees synchronised administration, increased stability, and higher absorption. Results: The co-delivery device, designed successfully, encapsulated both the antioxidant and the angiotensin II blocker, resulting in synchronised release kinetics. When compared to free medicines, in vitro tests demonstrated improved cellular absorption and a notable decrease in oxidative stress indicators. A strong and long-lasting drop in systolic blood pressure was observed in later in vivo pharmacodynamic experiments in hypertensive mouse models. Significantly, the formulation outperformed the therapeutic results of traditional monotherapy in terms of protection against vascular inflammation and end-organ damage, including cardiac fibrosis. These findings confirm the system's potential for multi-mechanistic, synergistic control of hypertension. Conclusions: In summary, this study validates a novel co-delivery method as a potentially practical treatment approach for hypertension. The platform exhibits substantial synergistic benefits by facilitating the synchronised delivery of an antioxidant and an angiotensin II blocker, resulting in improved blood pressure regulation and notable reduction of end-organ damage caused by oxidative stress. The results open the door for next-generation nanomedicines in cardiovascular disease by highlighting the benefits of a multi-targeted strategy over single-drug therapy. To translate these encouraging pre-clinical findings into tangible patient benefits, future research should focus on scaling up the formulation and progressing to clinical trials.
Banerjee et al. (Fri,) studied this question.