Lipid-Based Drug Delivery Systems forAntihypertensive Therapy: EmergingConcepts, Formulation Advances, andFuture Clinical Potential

Abstract

Hypertension still represents one of the most prevalent global health burdens with sustained hurdles for achieving
sufficient long-term control, because of poor compliance, dosing complexity, and oral drug pharmacokinetic
fluctuations. Lipid-based drug delivery systems (LBDDS) can be a potential solution to these problems for effective
treatment of hypertension by enhancing solubility, protection against pre-systemic metabolism, and promotion of
intestinal lymphatic transport, as well as the possibility of prolonged or site-specific release. Here, we offer a
synthesis of the current knowledge about the most important lipidic drug delivery platforms, respectively, liposomes,
solid lipid nanoparticles, nanostructured lipid carriers, lipid–polymer hybrid nanoparticles, and nanoemulsions,
addressing their structural aspects for antihypertensive therapeutic strategies, formulation constraints, and
activity potential against representative hypertensive drugs. Key formulation variables (lipid selection, surfactant
type, particle size, polydispersity index, and encapsulation efficiency) and stability challenges (lipid oxidation,
polymorphic transitions, surfactant hydrolysis, and drug expulsion) are examined alongside common excipients
and mitigation strategies such as antioxidants, mixed lipid matrices, and cryoprotectants. Translational barriers,
such as manufacturing scale-up, reproducibility, long-term safety, regulatory characterization requirements, and
economic considerations, are discussed, as are opportunities from microfluidic manufacturing, targeted surface
functionalization, and alternative administration routes (transdermal, buccal, and intranasal) to enable precision
dosing and rapid onset where needed. The review concludes that while robust pre-clinical data support the
pharmacokinetic and compliance advantages of LBDDS for antihypertensives, coordinated efforts in standardizing
characterization, validating in vitro–in vivo correlations, and conducting comparative clinical trials are essential
for clinical translation and adoption, particularly in resource-limited settings.