Design and optimization of hybrid lipid-polymeric nanoparticles for targeted drug delivery in cardiovascular diseases

Coronary heart disease (CHD), also known as ischemic heart disease (IHD), is a condition characterized by restricted blood flow to the heart muscle due to partial narrowing or complete blockage of the coronary arteries [1]. The coronary arteries are essential for maintaining heart health by ensuring a continuous blood supply. This blood delivers oxygen and vital nutrients to the myocardium, supporting proper heart function. Insufficient blood supply leads to severe complications, including myocardial necrosis and subsequent scarring, ultimately contributing to high morbidity and mortality worldwide, with approximately 18 million deaths annually [2]. Early diagnosis and effective therapeutic strategies are critical to mitigating disease progression. Nanoparticles have emerged as a promising approach for IHD management, offering advanced solutions for targeted drug delivery [3], imaging [4] and tissue regeneration[5]. Research has demonstrated that nanoparticle-based formulations can enhance the visualization of damaged myocardium while also improving the pharmacokinetic, physical and chemical properties of incorporated cardiological drugs in vivo. Our study aimed to optimize hybrid lipid-polymeric nanoparticles (HLPN) by varying lipid-to-polymer ratios (1:10, 1:5, 1:3, 2:5, 1:2, 3:5, 2:3, 3:4, 4:5, 1:1). Following synthesis, the most effective formulations, identified based on their physicochemical properties, were loaded with curcumin. Poly(lactic-co-glycolic acid), cholesterol and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy(polyethylene glycol)-2000] were used for the synthesis of HLPN. The size, polydispersity index (PdI) and zeta potential of nanoparticles were evaluated using the dynamic light scattering method. The colloidal stability of selected HLPN was determined in a cell growth medium for 72 hours. Curcumin entrapment in HLPN was measured by fluorescence spectroscopy and the entrapment efficiency was calculated based on the measured values. After synthesis, nanoparticles with sizes up to 150 nm were selected, and four different formulations (1:3, 1:2, 2:3, 1:1) were chosen for further experiments. Stability tests showed that the 1:1 formulation was characterized by a variation of PdI, and in the 2:3 formulation, there was a significant increase in particle size. The most stable formulations were the 1:2 and 1:3. When curcumin was incorporated into the 1:2 and 1:3 nanoparticles, the 1:3 formulation, with a higher polymer content, showed a greater curcumin entrapment efficiency of 64 %, compared to 55 % for the 1:2 formulation. In conclusion, the 1:3 nanoparticle formulation was the most suitable for further studies, showing enhanced stability and curcumin entrapment efficiency.