Potential Strategies to Reduce Blood Pressure in Treatment-Resistant Hypertension Using Food and Drug Administration–Approved Nanodrug Delivery Platforms

Abstract

Unmet medical need Despite significant progress in pharmacological management of patients with primary hypertension, treatment-resistant hypertension (TRH) is still relatively prevalent among them (1). This condition is defined as blood pressure that remains above goal despite concurrent use of optimal doses of three anti-hypertensive drugs of different classes and exclusion of secondary causes of hypertension (2). Current evidence-based pharmacological approach to TRH targets 3 well-established pathophysiological mechanisms thought to underlie this condition simultaneously: increased sodium and fluid retention, enhanced activation of renin-angiotensin system, and over-reactive sympathetic nervous system (3, 4). Thus, patients with TRH are presently treated with combined daily oral diuretics, angiotensin converting enzyme (ACE) inhibitors/angiotensin receptor blockers and calcium channel blockers (5). If blood pressure remains persistently elevated, daily oral spironolactone, an antagonist of aldosterone receptors, is then added to the 3-drug regimen, which provides significant benefit to patients with hyperaldosteronism (2). However, this poly-pharmacopeia approach is not only insufficient to adequately control blood pressure in a significant population of TRH patients but may also expose patients with TRH to serious adverse events and drug interactions leading eventually to non-adherence and treatment failure. Hence, despite recent advances in hypertension research and therapeutics, TRH still represents a life-threatening medical problem. Consequently, there is an urgent need to develop and test novel, safe and efficacious drugs for TRH to improve long-term clinical management and outcomes of patients. Unfortunately, accomplishing this goal is challenging because current drug development

Reactive Oxygen Species Scavenging Nanomedicine for the Treatment of Ischemic Heart Disease

“…Nanomedicines for the Treatment of Diabetes, Hypertension, and Hypercholesterolemia Nanomaterials such as liposome, polymer, and nanocrystalbased nanocarriers are the most commonly used FDA-approved nanotechnology-based drug delivery platforms for the treatment of diabetes, hypertension, and hypercholesterolemia. [256]…”

“…Nanomaterials such as liposome, [287,288] PLGA, [284,285] chitosan, PLA, [283] and poly(εcaprolactone (PCL) [286] have shown efficient and controlled delivery of these drugs for a better control of blood pressure in animal model of hypertension. [256] The major advantage of using nanomedicine is its ability to manage BP fluctuations by maintaining high and prolonged plasma drug concentrations with lower drug dosage. For instance, a poly(acrylic acid)-modified MoS 2 nanoparticle (PAA-MoS 2 NP)-based transdermal-drug delivery system (TDDS) was developed by He and co-authors.…”

The link between immunity and hypertension in the kidney and heart

“…Even current FDA approved anti-hypertensives may mediate some of their beneficial effects through immune modulation, but further studies are needed for confirmation ( 157 ). Targeting the immune system to lower blood pressure and reduce organ damage has proven complicated ( 201 , 202 ), but organ specific immune targeting using nanotechnology appears to be a promising solution to reduce toxicities ( 155 , 199 ). Recent identification of single nucleotide polymorphisms in SH2B adaptor protein 3 contributing to T cell involvement in hypertension and renal damage ( 203 ) further complicates therapeutic targeting as genetic mutations may predispose certain immune cells to promote inflammation, supporting consideration of individual patient genetic predispositions when identifying driving factors of hypertension to design future treatment plans, as is becoming increasingly debated ( 204 ).…”

“…Further studies are needed to address the potential effectiveness of alternative immunosuppressant therapies in reducing blood pressure. Several promising pre-clinical studies have been conducted indicating the feasibility of using FDA-approved nanodrug platforms to deliver tissue specific immunosuppressant therapy (minimizing off-target toxicities), but further validation and studies are required before use in a clinical setting ( 199 ). Regardless of current difficulties, targeted immunosuppression to reduce inflammation and immune-mediated organ dysfunction in hypertension continues to be of scientific interest.…”

Extracellular Vesicles in Cardiovascular Diseases: Alternative Biomarker Sources, Therapeutic Agents, and Drug Delivery Carriers

“…Being synthetic in nature, the properties of liposomes are highly tunable: Liposomes can be easily functionalized at their surface with different moieties to achieve different purposes (e.g., incorporation of ligands targeting receptors that are overexpressed in pathological conditions). Though to the best of our knowledge, there is no FDA-approved nano-formulation for the treatment of CVD [149,150], liposomes have been demonstrated to improve the therapeutic outcomes in several animal studies of CVD (Table 2).…”