Peptide-Based HDL as an Effective Delivery System for Lipophilic Drugs to Restrain Atherosclerosis Development

Abstract

Purpose Peptide-based high-density lipoprotein (pHDL) structurally and functionally resembles the natural HDL as anti-atherosclerosis (AS) therapies. Since pHDL contains a large hydrophobic core, this study aims to evaluate the potentials of pHDL as a hydrophobic drug carrier and the efficiency of drug-loaded pHDL in the control of AS. Methods The pHDL encapsulation of hydrophobic components from natural plants, including curcumin (Cur) and tanshinone IIA (TanIIA), was achieved using one-step microfluidics. Then, morphological features and loading efficiencies of pHDL-Cur and pHDL-TanIIA were determined by TEM and high-performance liquid chromatography (HPLC), respectively. Taking the fluorescence advantage of Cur, localizations of loaded Cur in pHDL were investigated by fluorescence quenchers, and recruitments of Cur to AS plaques were assessed with ex vivo imaging. Based on anti-inflammatory properties of TanIIA, pHDL-TanIIA was accordingly developed to evaluate the anti-AS effects through examinations of plasma lipid parameters and pathological alterations of plaque-associated regions. Results Both lipophilic Cur and TanIIA can be efficiently loaded into pHDL carriers. The resultant pHDL-Cur and pHDL-TanIIA inherit the homogeneous nano-disk structure of pHDL. By using pHDL-Cur, the encapsulated hydrophobics are tracked in the core of pHDL, and incorporations of Cur with pHDL vehicles greatly improve the bioavailability and association of Cur with AS plaques. Moreover, when loaded with TanIIA, which has established its role in anti-AS as an anti-inflammatory candidate, synergistic effects in reducing AS lesions and improving pathological alterations of main organs related to AS were achieved. Conclusion The pHDL system could potentially be applied for both imaging and therapy in animal models of AS. Benefits of pHDL-based drug delivery will potentially extend the application scenarios of bioactive chemicals from natural plants which are underutilized due to features like low bioavailability and facilitate the clinical translation of synthetic HDL therapies in HDL-associated disorders, including but not limited to AS.

Recent Advances in Anti‐Atherosclerosis and Potential Therapeutic Targets for Nanomaterial‐Derived Drug Formulations

“…The results showed that free curcumin reached its maximum blood concentration in 1 h, while the pHDL nanoparticles reached their maximum concentration in 8 h, significantly extending the internal circulation time of the curcumin. [ 179 ] Nanodelivery systems can also improve the biosafety of drugs. For example, Zheng et al.…”

“…The results showed that free curcumin reached its maximum blood concentration in 1 h, while the pHDL nanoparticles reached their maximum concentration in 8 h, significantly extending the internal circulation time of the curcumin. [179] Nanodelivery systems can also improve the biosafety of drugs. For example, Zheng et al prepared a urease-catalase, micromotordriven NE nanodrug delivery system by asymmetrically immobilizing the enzyme on the surface of the natural NE and then loading urokinase (UK) coupled silver (Ag) nanoparticles (Ag UK), and the results showed that nanodelivery systems could significantly reduce hemorrhagic side effects.…”