Title : Development and evaluation of dapagliflozin-loaded bilosomal nanocarriers for enhanced cardioprotection in rat model of isoproterenol-induced heart failure
Abstract:
Heart Failure (HF) remains a leading cause of morbidity and mortality worldwide, necessitating innovative therapeutic strategies. Dapagliflozin (DAPA), an SGLT2 inhibitor, has emerged as a groundbreaking agent with proven cardioprotective effects. However, clinical utility is hampered by poor solubility, hygroscopicity, and low bioavailability, limiting its full therapeutic potential.
In this pioneering study, we developed the first bile salt-stabilized nanovesicular system (DAPA-BIL-NF) designed to overcome these limitations. Using a meticulous Box–Behnken optimization approach, we produced nanovesicles approximately 20.9 nm in size, with a zeta potential of –41.69 mV, and an encapsulation efficiency of 92.8%. These nanocarriers were comprehensively characterized via TEM, XRD, and FTIR, confirming their nanoscale morphology, amorphous nature, and molecular stability—crucial for enhanced delivery.
In vitro assessments demonstrated biphasic, sustained drug release, while confocal microscopy revealed significantly improved intestinal permeation and tissue penetration twice that of free dye. In vivo experiments using a rat model of isoproterenol-induced HF showed that DAPA-BIL-NF markedly improved antioxidant enzyme levels, reduced lipid peroxidation, and mitigated cardiac injury and fibrosis. This innovative nanoplatform represents a first-of-its-kind approach to amplifying SGLT2 inhibitor efficacy in cardiovascular disease, paving the way for next-generation, nanotechnology-driven HF therapies with superior bioavailability and therapeutic outcomes.
