Hyperuricemia, a prevalent metabolic dysfunction, outcomes from dysfunction within the manufacturing and excretion of uric acid (UA) contained in the physique [1], [2]. Hyperuricemia has a variety of issues, together with gout [3], hypertension [1], atherosclerosis [4], cardiovascular ailments [2], diabetes [5] and metabolic syndrome [6]. Epidemiological research point out that hyperuricemic nephropathy (HUN) can also be a serious complication of hyperuricemia, which is said to lipid peroxidation attributable to the massive quantity of urate deposited contained in the kidney [7], [8]. The imbalance between oxidants and antioxidants within the physique can result in oxidative stress response, wherein reactive oxygen species (ROS) are a key issue [9], [10]. Earlier research confirmed that UA may cause lipid peroxidation by growing ROS degree (Scheme 1A), which is crucial for the event and development of HUN [11], [12]. As well as, extreme ROS can also result in M1-macrophage polarization, thereby inflicting inflammatory infiltration and apoptosis, which additional exacerbate HUN [13], [14]. Consequently, aside from decreasing the UA degree, modulating lipid peroxidation and macrophage infiltration by scavenging extreme ROS has turn out to be a possible technique for ameliorating HUN.
Puerarin (PEA) is a typical isoflavone compound extracted from Pueraria root (Kudzu). Fashionable pharmacological research confirmed that PEA reveals a myriad of organic actions, resembling anti-inflammatory, antitumor, and antidiabetic [15], [16]. Our earlier analysis has proven that PEA cannot solely inhibit the manufacturing of uric acid but additionally promote its excretion, thereby exerting anti-hyperuricemic exercise [17]. On the similar time, PEA reveals glorious antioxidant exercise, which is carefully associated to the molecular construction. The polyphenol construction of PEA may present lively protons that would react with free radicals to supply steady merchandise, thus blocking the automated oxidation means of lipids [18], [19]. Nevertheless, as a result of presence of a number of benzene rings and hydroxyl teams, PEA reveals poor water-solubility, limiting its bioavailability. As well as, PEA may be very delicate to pH, with a brief half-life in aqueous resolution at physiological pH worth [20]. Makes an attempt to enhance the bioavailability and scientific results of PEA have been reported within the literature utilizing drug provider applied sciences. These supplies embrace nanocrystals [21], nanosuspensions [20], microemulsions [22], and stable lipid nanoparticles [23]. Nonetheless, limitations of those approaches embrace excessive provider demand, structural intricacy, and uncontrolled drug launch. Due to this fact, growing a novel drug supply system to extend retention length and improve the bioavailability of PEA is essential for the environment friendly therapy of HUN.
Nanoparticles (NPs) characterize a flexible and efficient platform for delivering medication, which may successfully enhance the solubility whereas conferring domestically therapeutic results of drug molecules [24]. Self-assembled NPs, as an rising technique, maintain nice potential for enhancing drug efficacy and drug-loading capability. [25], [26]. Hyaluronic acid (HA) is a pure polysaccharide distributed in extracellular matrix and synovial fluid with glorious biocompatibility and biodegradability [27], [28]. HA has good water solubility, and the abundance of carboxyl and hydroxyl teams makes it appropriate for chemical modification, which may considerably enhance the water solubility of hydrophobic compounds by means of polymerization reactions [29]. On the similar time, HA is ready to endure self-assembly to type nanoparticles, which in flip improves the soundness of its sure medication [30], [31]. Extra importantly, earlier research revealed {that a} typical characteristic of kidney harm is the abnormally elevated expression of the CD44 receptor on the cell membrane of renal tubular epithelial cells [32], [33]. HA may enhance the focusing on of drug molecules by means of particular recognition of CD44 receptors, thus realizing exact and environment friendly therapy of kidney illness [34], [35]. These properties set up HA as a horny candidate for nano-delivery supplies, which might be utilized within the building of focused drug supply techniques for kidney ailments.
On this examine, to enhance the bioavailability of PEA, PEA-loaded HA self-assembled nanoparticles (PEA-HA NPs) have been developed for the environment friendly therapy of HUA (Scheme 1B-C). PEA-HA copolymer was ready by the Yamaguchi response, and PEA-HA NPs have been ready by self-assembly. Initially, the physicochemical properties and pH-responsive strategy of PEA-HA NPs have been investigated. As well as, the renal targetability of PEA-HA NPs was studied in regular and mannequin mice. Lastly, the therapeutic impact of PEA-HA NPs on HUN was evaluated in cells and mouse experiments.
