Quercetin (QUE) is a flavonol that has recently received great attention from the research community due to its important pharmacological properties. However, QUE’s low solubility and extended first-pass metabolism limit its oral administration. This review aims to present the potential of various nanoformulations in the development of QUE dosage forms for bioavailability enhancement. Advanced drug delivery nanosystems can be used for more efficient encapsulation, targeting, and controlled release of QUE. An overview of the primary nanosystem categories, formulation processes, and characterization techniques are described. In particular, lipid-based nanocarriers, such as liposomes, nanostructured-lipid carries, and solid-lipid nanoparticles, are widely used to improve QUE’s oral absorption and targeting, increase its antioxidant activity, and ensure sustained release. Moreover, polymer-based nanocarriers exhibit unique properties for the improvement of the Absorption, Distribution, Metabolism, Excretion, and Toxicology (ADME(T)) profile. Namely, micelles and hydrogels composed of natural or synthetic polymers have been applied in QUE formulations. Furthermore, cyclodextrin, niosomes, and nanoemulsions are proposed as formulation alternatives for administration via different routes. This comprehensive review provides insight into the role of advanced drug delivery nanosystems for the formulation and delivery of QUE.

Quercetin, as a member of flavonoids, has emerged as a potential therapeutic agent in cardiovascular diseases (CVDs) in recent decades. In this comprehensive literature review, our goal was a critical appraisal of the pathophysiological mechanisms of quercetin in relation to the classical cardiovascular risk factors (e.g., hyperlipidemia), atherosclerosis, etc. We also assessed experimental and clinical data about its potential application in CVDs. Experimental studies including both in vitro methods and in vivo animal models mainly outline the following effects of quercetin: (1) antihypertensive, (2) hypolipidemic, (3) hypoglycemic, (4) anti-atherosclerotic, and (5) cardioprotective (suppressed cardiotoxicity). From the clinical point of view, there are human studies and meta-analyses implicating its beneficial effects on glycemic and lipid parameters. In contrast, other human studies failed to demonstrate consistent favorable effects of quercetin on other cardiometabolic risk factors such as MS, obesity, and hypertension, underlying the need for further investigation. Analyzing the reason of this inconsistency, we identified significant drawbacks in the clinical trials’ design, while the absence of pharmacokinetic/pharmacodynamic tests prior to the studies attenuated the power of clinical results. Therefore, additional well-designed preclinical and clinical studies are required to examine the therapeutic mechanisms and clinical efficacy of quercetin in CVDs.

Hydrogels are three-dimensional polymeric systems, being able to accommodate different categories of bioactive agents and act as promising drug delivery systems in many different biomedical applications. Due to their extended 3D network, hydrogels exhibit many advantages, such as extensive loading capacity and controlled drug release profiles, combined with characteristics such as biocompatibility and biodegradability, due to their constructive polymeric biomaterials. Moreover, hydrogels are capable of being administered via different routes of administration, including systemic and topical ones, due to their tunable characteristics. Stimuli-responsive hydrogels are characterized as smart biomaterials, while environmental stimuli, such as pH, can be employed to trigger on-demand drug release from the hydrogels via the provocation of conformational changes. In the present study, an emphasis on the pH-responsive hydrogels is taking place through various literature cases in drug delivery, wound healing, and some alternative applications, including implantation, oral administration, etc., wherein many different polymeric derivatives have been utilized. Moreover, the role of each used polymer or polymeric combination with other functional biomaterials, their mode of structure formation (for example, crosslinking), and their content release mechanism are highlighted, as well as the therapeutic effect of the hydrogels on different pathological conditions, as promising candidates for pharmaceutical applications.