Protective effects on myocardial infarction model: delivery of schisandrin B using matrix metalloproteinase-sensitive peptide-modified, PEGylated lipid nanoparticles

Abstract

Purpose Schisandrin B (Sch B) is clinically applied for the treatment of hepatitis and ischemic disease. However, its clinical efficacy is limited due to the poor solubility and low bioavailability. This study aimed to develop matrix metalloproteinase (MMP)-sensitive peptide-modified, polyethylene glycol (PEG)-modified (PEGylated) solid lipid nanoparticles (SLNs) for loading Sch B (MMP-Sch B SLNs), and to evaluate the therapeutic effect in the myocardial infarction model. Methods PEG lipid and MMP-targeting peptide conjugate were synthesized. MMP-Sch B SLNs were prepared by solvent displacement technique. The physicochemical properties and pharmacokinetics of SLNs were investigated. In vivo effects on infarct size was evaluated in rats. Results The successful synthesis of lipid-peptide conjugate was confirmed. MMP-Sch B SLNs had a particle size of 130 nm, a zeta potential of 18.3 mV, and a sustained-release behavior. Higher heart drug concentration and longer blood circulation times were achieved by Sch B loaded SLNs than the drug solution according to the pharmacokinetic and biodistribution results. The best therapeutic efficacy was exhibited by MMP-Sch B SLNs by reducing the infarction size to the greatest extent. Conclusion The modified SLNs may be a good choice for delivery of Sch B for the treatment of myocardial infarction.

Evaluation of the potential of nanoparticles containing active substances in selected chronic diseases

“…37 Shao et al investigated the therapeutic effect of Schisandrin B (Sch B) in the form of SLN in the model of the rat myocardial infarction. 38 Schisandrin B is isolated from the fruit of Schisandra chinensis and can be clinically applied in myocardial ischemia. Polyethylene glycol (PEG) and matrix metalloproteinase-targeting peptide (MMP-TP) conjugate was synthesized in the study.…”

“…The authors demonstrated that the developed formulation is the optimal carrier of API for the myocardium tissues and effectively protects the heart against acute myocardial infarction. 38 The possibility of using porous silicon nanoparticles (PSi) in cardiovascular disease therapy was also assessed. The Finnish team attempted to develop PSi-based nanosystems for targeted therapy and diagnosis of myocardial infarction.…”

“…In the case of fullerenes, the data indicated that anticancer drugs conjugated with fullerenes may decrease their cytotoxicity on account of their role as radical sponges. 38,39 In the study of Chaudhuri et al, 59 conjugate of fullerenoldoxorubicin (DOX) inhibited the proliferation of cancer cells in vitro, blocked the G2-M cell cycle and induced the process of apoptosis. The authors did not observe any toxicity of the obtained nanosystem, which even demonstrated its protective effect on cardiac muscle, kidney, lung, as well as venereal cells.…”

Targeting Nanotechnologies for the Treatment of Thrombosis and Cardiovascular Disease

“…Shao et al showed that the antioxidant and anti-inflammatory agent Schisandrin B's (Sch B's) encapsulation within a matrix-metalloproteinasesensitive peptide-modified and PEG-modified (PEGylated) solid lipid nanoparticle (MMP-Sch B SLN) leads to promising in vitro and in vivo outcomes in the context of treating MI. 41 Shao et al demonstrated that their novel formulation of MMP-Sch B SLN significantly reduced the percentage of infarct sizes relative to the Sch B solution and saline control (19.2, 36.5, and 43.2%, respectively) in rat MI models. 41 Furthermore, through their pharmacokinetic and biodistribution experiments, the authors have further demonstrated that the encapsulation of Sch B into their lipid-based carrier yields improved therapeutic characteristics, such as a prolonged plasma circulation time of encapsulated Sch B (up to more than 48 hours) when compared with Sch B solution (cleared from circulation within 4 hours).…”

“…41 Shao et al demonstrated that their novel formulation of MMP-Sch B SLN significantly reduced the percentage of infarct sizes relative to the Sch B solution and saline control (19.2, 36.5, and 43.2%, respectively) in rat MI models. 41 Furthermore, through their pharmacokinetic and biodistribution experiments, the authors have further demonstrated that the encapsulation of Sch B into their lipid-based carrier yields improved therapeutic characteristics, such as a prolonged plasma circulation time of encapsulated Sch B (up to more than 48 hours) when compared with Sch B solution (cleared from circulation within 4 hours). Additionally, Zhang et al demonstrated that the encapsulation of the antioxidant baicalin (BN) within non-PEGylated and PEGylated nanostructured lipid carriers (BN-NLC and BN-PEG-NLC, respectively) functioned as viable therapies for MI, with the BN-PEG-NLC showing as the most promising therapeutic characteristics.…”