Search Results (15)

Quercetin (Que) is widely recognized for its antioxidant and neuroprotective properties; however, its clinical potential remains limited due to poor solubility and low oral bioavailability. Nasal powders have emerged as a promising strategy to overcome these limitations, taking advantage of nose-to-brain delivery, offering a direct, non-invasive route to the central nervous system while bypassing first-pass metabolism. This study aims to extend previous work by systematically investigating the impact of different preparation methods (spray drying vs. lyophilization) and the incorporation of hydroxypropyl methylcellulose (HPMC) and mannitol/lecithin microparticles (MLMPs) on the physicochemical characteristics, structural properties, and in vitro diffusion behavior of HPβCD-based nasal powder formulations of Que. Thermal behavior and stability were analyzed using TGA, while morphology and particle distribution were assessed via Scanning Electron Microscopy. In vitro diffusion studies using Franz cells and regenerated cellulose membranes were conducted under simulated nasal conditions. Among all tested formulations, the spray-dried HPβCD/Que powder (F4) showed the highest permeation (0.11 ± 0.01 mg/cm² at 120 min). The inclusion of HPMC improved thermal stability but reduced Que diffusion, likely due to increased viscosity and matrix formation. Blending with MLMPs enhanced powder flow and dose placement, although it modestly reduced diffusion efficiency. Overall, this study highlights the potential of HPβCD-based spray-dried powders for nasal Que delivery and demonstrates how HPMC and MLMPs can be strategically employed to tailor performance characteristics. Full article

Donepezil (DH), a selective acetylcholinesterase inhibitor, is widely used to manage symptoms of mild to moderate Alzheimer’s disease by enhancing cholinergic neurotransmission and preventing acetylcholine breakdown. Despite the effectiveness of oral formulations, extensive hepatic metabolism and low systemic bioavailability have driven the search for alternative delivery systems. This study focuses on nasal delivery as a non-parenteral substitute, utilizing hydroxypropyl methylcellulose (HPMC) for its mucoadhesive properties and methyl-β-cyclodextrin (Me-β-CD) for its ability to enhance permeability and form inclusion complexes with drugs. Prior studies demonstrated the potential of HPMC-based nasal films for nose-to-brain delivery of donepezil and highlighted Me-β-CD’s role in improving drug solubility. Building on this, transparent gel formulations containing DH, HPMC, and 2,6 Me-β-CD were developed to investigate molecular interactions within two- and three-component systems. This study utilized a combination of nuclear magnetic resonance (NMR) spectroscopy and density functional theory (DFT) to provide detailed insights into the interactions between DH, 2,6-Me-β-CD, and HPMC. The findings provide critical insights into drug–excipient interactions, aiding the optimization of stability, solubility, and controlled release. This advances the rational design of nanotechnology-based drug delivery systems for enhanced therapeutic efficacy. Full article

Background/Objectives: Non-alcoholic fatty liver disease (NAFLD) is a major metabolic disorder with no established pharmacotherapy. Quercetin, a polyphenolic flavonoid, demonstrates potential hepatoprotective effects but has limited bioavailability. This study evaluates the impact of quercetin on NAFLD and assesses the roles of autophagy-related proteins in disease progression. Methods: Forty-seven male C57BL/6J mice were fed a high-fat diet (HFD) for 12 weeks to induce NAFLD, followed by quercetin treatment for 4 weeks. Mice were divided into baseline, control, and two quercetin groups, receiving low (10 mg/kg) and high (50 mg/kg) doses. Liver histology was scored using the NAFLD Activity Score (NAS). Immunohistochemistry and immunoblotting were performed to analyze autophagy markers. Results: Quercetin-treated groups showed significant reductions in NAS compared to controls (p = 0.011), mainly in steatosis and steatohepatitis. Immunohistochemistry indicated increased expression of autophagy markers LCA and p62 in quercetin groups. Western blot analysis revealed significant elevations in LC3A in the treated groups, suggesting improved autophagic activity and lipid degradation. Conclusions: Quercetin effectively reduces NAFLD severity and modulates autophagy-related proteins. These findings suggest that quercetin enhances autophagic flux, supporting its therapeutic potential for NAFLD. Additional research is needed to clarify the molecular mechanisms of quercetin and to determine the optimal dosing for clinical application. Full article

Ropinirole is a non-ergolinic dopamine agonist used to manage Parkinson’s disease and it is characterized by poor oral bioavailability. This study aimed to design and develop advanced drug delivery systems composed of poloxamer 407, a non-ionic surfactant (Tween 80), and cyclodextrins (methyl-β-CD or hydroxy-propyl-β-CD) for possible brain targeting of ropinirole after nasal administration for the treatment of Parkinson’s disease. The hybrid systems were formed by the thin-film hydration method, followed by an extensive physicochemical and morphological characterization. The in vitro cytotoxicity of the systems on HEK293 cell lines was also tested. In vitro release and ex vivo mucosal permeation of ropinirole were assessed using Franz cells at 34 °C and with phosphate buffer solution at pH 5.6 in the donor compartment, simulating the conditions of the nasal cavity. The results indicated that the diffusion-controlled drug release exhibited a progressive increase throughout the experiment, while a proof-of-concept experiment on ex vivo permeation through rabbit nasal mucosa revealed a better performance of the prepared hybrid systems in comparison to ropinirole solution. The encouraging results in drug release and mucosal permeation indicate that these hybrid systems can serve as attractive platforms for effective and targeted nose-to-brain delivery of ropinirole with a possible application in Parkinson’s disease. Further ex vivo and in vivo studies to support the results of the present work are ongoing. Full article

Intranasal (IN) administration has emerged as a novel approach for rapid systemic absorption, with potential applicability in the management of acute cardiovascular events. This review explores the evolution of IN cardiovascular pharmacotherapy, emphasizing its potential in achieving systemic effects and bypassing the first-pass metabolism associated with oral administration. The extensive vascularization of nasal mucosa and a porous endothelial basement membrane facilitate efficient drug absorption into the bloodstream. The IN route ensures a critical swift onset of action, which allows self-administration in at-home settings. For instance, etripamil nasal spray, a first-in-class formulation, exemplifies the therapeutic potential of this approach in the treatment of spontaneous supraventricular tachycardia. The review critically assesses studies on IN formulations for angina, acute myocardial infarction, hypertensive episodes, and cardiac arrhythmias. Preclinical evaluations of beta-blockers, calcium-channel blockers, and antianginal drugs demonstrate the feasibility of IN administration for acute cardiovascular events. A small number of clinical trials have revealed promising results, emphasizing the superiority of IN drug delivery over oral administration in terms of bioavailability and onset of action. Unambiguously, the limited clinical trials and patient enrollment pose challenges in generalizing experimental outcomes. However, the nose-to-heart approach has clinical potential. Full article

Quercetin (Que) is one of the most studied flavonoids with strong antioxidant properties ascribed to its ability to bind free radicals and inactivate them. However, the low solubility of the compound along with its inadequate absorption after oral administration limit its beneficial effects. Que’s complexation with two different cyclodextrin (CD) derivatives (hydroxypropyl-β-CD and methyl-β-CD) via the neutralization/lyophilization method has been found to improve its physicochemical properties. Moreover, blends of the lyophilized powders with mannitol/lecithin microparticles (MLMPs) have been proposed as candidates for intranasal (IN) administration after in vitro and ex vivo evaluations. In this context, a comparative pharmacokinetic (PK) study of the IN vs oral administration of Que lyophilized powders and their blends with MLMPs (75:25 w/w) was performed on Wistar rats. The PK parameters estimated by a non-compartmental analysis using the sparse data methodology in Phoenix^® 8.3 (Certara, Princeton, NJ, USA) illustrated the effectiveness of IN administration either in brain targeting or in reaching the bloodstream. Significant levels of the compound were achieved at both sites, compared to those after oral delivery which were negligible. These results favor the potential application of the prepared Que nasal powders for systemic and nose-to-brain delivery for the prevention and/or treatment of neuroinflammatory degenerative conditions, such as Parkinson’s and Alzheimer’s disease. Full article

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. Full article

Intranasal delivery is a non-invasive mode of administration, gaining popularity due to its potential for targeted delivery to the brain. The anatomic connection of the nasal cavity with the central nervous system (CNS) is based on two nerves: olfactory and trigeminal. Moreover, the high vasculature of the respiratory area enables systemic absorption avoiding possible hepatic metabolism. Due to these physiological peculiarities of the nasal cavity, compartmental modeling for nasal formulation is considered a demanding process. For this purpose, intravenous models have been proposed, based on the fast absorption from the olfactory nerve. However, most of the sophisticated approaches are required to describe the different absorption events occurring in the nasal cavity. Donepezil was recently formulated in the form of nasal film ensuring drug delivery in both bloodstream and the brain. In this work, a three-compartment model was first developed to describe donepezil oral brain and blood pharmacokinetics. Subsequently, using parameters estimated by this model, an intranasal model was developed dividing the administered dose into three fractions, corresponding to absorption directly to the bloodstream and brain, as well as indirectly to the brain expressed through transit compartments. Hence, the models of this study aim to describe the drug flow on both occasions and quantify the direct nose-to-brain and systemic distribution. Full article

Echinochrome A (EchA), a marine bioactive pigment isolated from various sea urchin species, is the active agent of the clinically approved drug Histochrome^®. EchA is currently only available in the form of an isotonic solution of its di- and tri-sodium salts due to its poor water solubility and sensitivity to oxidation. Electrospun polymeric nanofibers have lately emerged as promising drug carriers capable of improving the dissolution and bioavailability of drugs with limited water solubility. In the current study, EchA isolated from sea urchins of the genus Diadema collected at the island of Kastellorizo was incorporated in electrospun micro-/nanofibrous matrices composed of polycaprolactone and polyvinylpyrrolidone in various combinations. The physicochemical properties of the micro-/nanofibers were characterized using SEM, FT-IR, TGA and DSC analyses. The fabricated matrices exhibited variable dissolution/release profiles of EchA, as evidenced in in vitro experiments using gastrointestinal-like fluids (pH 1.2, 4.5 and 6.8). Ex vivo permeability studies using the EchA-loaded micro-/nanofibrous matrices showed an increased permeation of EchA across the duodenum barrier. The results of our study clearly show that electrospun polymeric micro-/nanofibers represent promising carriers for the development of new pharmaceutical formulations with controlled release, as well as increased stability and solubility of EchA, suitable for oral administration, while offering the potential for targeted delivery. Full article

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. As a result, pharmaceutical and non-pharmaceutical interventions modifying risk factors for CVDs are a top priority of scientific research. Non-pharmaceutical therapeutical approaches, including herbal supplements, have gained growing interest from researchers as part of the therapeutic strategies for primary or secondary prevention of CVDs. Several experimental studies have supported the potential effects of apigenin, quercetin, and silibinin as beneficial supplements in cohorts at risk of CVDs. Accordingly, this comprehensive review focused critically on the cardioprotective effects/mechanisms of the abovementioned three bio-active compounds from natural products. For this purpose, we have included in vitro, preclinical, and clinical studies associated with atherosclerosis and a wide variety of cardiovascular risk factors (hypertension, diabetes, dyslipidemia, obesity, cardiac injury, and metabolic syndrome). In addition, we attempted to summarize and categorize the laboratory methods for their isolation and identification from plant extracts. This review unveiled many uncertainties which are still unexplored, such as the extrapolation of experimental results to clinical practice, mainly due to the small clinical studies, heterogeneous doses, divergent constituents, and the absence of pharmacodynamic/pharmacokinetic analyses. Full article

The simultaneous administration of three antiplatelet agents has been proposed as an efficient strategy for the secondary prevention of atherothrombotic events and is included in the European guidelines. However, this strategy presented an increased risk of bleeding; therefore, the identification of new antiplatelet agents, with improved efficacy and diminished side effects, is of great importance. In silico studies, UPLC/MS Q-TOF plasma stability, in vitro platelet aggregation experiments, and pharmacokinetic studies were exploited. In the present study, it has been predicted that the flavonoid apigenin could target different platelet activation pathways, including P2Y12, protease-activated receptor-1 (PAR-1), and cyclooxygenase 1 (COX-1). To enhance apigenin’s potency, hybridization with docosahexaenoic acid (DHA) was performed, as fatty acids have illustrated potent efficacy against cardiovascular diseases (CVDs). The new molecular hybrid, termed 4′-DHA-apigenin, demonstrated enhanced inhibitory activity against platelet aggregation induced by thrombin receptor activator peptide-6 (TRAP-6), adenosine diphosphate (ADP), and arachidonic acid (AA), with respect to the parent apigenin. The 4′-DHA-apigenin hybrid illustrated an almost 2-fold enhanced inhibitory activity, with respect to apigenin, and an almost 3-fold enhanced inhibitory activity, with respect to DHA, for the ADP-induced platelet aggregation. Additionally, the hybrid presented a more than 12-fold enhanced inhibitory activity with respect to DHA for the TRAP-6 induced platelet aggregation. Furthermore, a 2-fold enhanced inhibitory activity was recorded for the 4′-DHA-apigenin hybrid for the AA-induced platelet aggregation with respect to apigenin. To surmount the reduced LC-MS based plasma stability, a novel dosage form in olive oil has been developed. The 4′-DHA-apigenin olive oil-based formulation presented an enhanced antiplatelet inhibitory effect in three activation pathways. To further explore the pharmacokinetic profile of 4′-DHA-apigenin in olive oil formulations, a UPLC/MS Q-TOF protocol has been established to quantify the serum levels of apigenin after oral administration to C57BL/6J wild type mice. The olive oil-based formulation of 4′-DHA-apigenin demonstrated an increase in apigenin bioavailability of 262 %. This study may offer a new therapeutic strategy tailored to improve the treatment of CVDs. Full article

Aspirin is an historic blockbuster product, and it has been proposed in a wide range of formulas. Due to exacerbation risks, the pulmonary route has been seldom considered as an alternative to conventional treatments. Only recently, owing to overt advantages, inhalable acetylsalicylic acid dry powders (ASA DPI) began to be considered as an option. In this work, we developed a novel highly performing inhalable ASA DPI using a nano spray-drying technique and leucine as an excipient and evaluated its pharmacokinetics compared with oral administration. The formulation obtained showed remarkable respirability and quality features. Serum and lung ASA DPI profiles showed faster presentation in blood and higher retention compared with oral administration. The dry powder was superior to the DPI suspension. The relative bioavailability in serum and lungs claimed superiority of ASA DPI over oral administration, notwithstanding a fourfold lower pulmonary dose. The obtained ASA DPI formulation shows promising features for the treatment of inflammatory and infectious lung pathologies. Full article

Quercetin (QUE) is a well-known natural product that can exert beneficial properties on human health. However, due to its low solubility its bioavailability is limited. In the present study, we examine whether its formulation with two cyclodextrins (CDs) may enhance its pharmacological profile. Comparative interaction studies of quercetin with 2-hydroxyl-propyl-β-cyclodextrin (2HP-β-CD) and 2,6-methylated cyclodextrin (2,6Me-β-CD) were performed using NMR spectroscopy, DFT calculations, and in silico molecular dynamics (MD) simulations. Using T1 relaxation experiments and 2D DOSY it was illustrated that both cyclodextrin vehicles can host quercetin. Quantum mechanical calculations showed the formation of hydrogen bonds between QUE with 2HP-β-CD and 2,6Μe-β-CD. Six hydrogen bonds are formed ranging between 2 to 2.8 Å with 2HP-β-CD and four hydrogen bonds within 2.8 Å with 2,6Μe-β-CD. Calculations of absolute binding free energies show that quercetin binds favorably to both 2,6Me-β-CD and 2HP-β-CD. MM/GBSA results show equally favorable binding of quercetin in the two CDs. Fluorescence spectroscopy shows moderate binding of quercetin in 2HP-β-CD (520 M⁻¹) and 2,6Me-β-CD (770 M⁻¹). Thus, we propose that both formulations (2HP-β-CD:quercetin, 2,6Me-β-CD:quercetin) could be further explored and exploited as small molecule carriers in biological studies. Full article

The objective and novelty of the present study is the development and optimization of innovative nasal film of Donepezil hydrochloride (DH) for potential use in Alzheimer’s disease. Hydroxypropyl-methyl-cellulose E50 (factor A) nasal films, with Polyethylene glycol 400 as plasticizer (factor B), and Methyl-β-Cyclodextrin, as permeation enhancer (factor C), were prepared and characterized in vitro and ex vivo. An experimental design was used to determine the effects of the selected factors on permeation profile of DH through rabbit nasal mucosa (response 1), and on film flexibility/foldability (response 2). A face centered central composite design with three levels was applied and 17 experiments were performed in triplicate. The prepared films exhibited good uniformity of DH content (90.0 ± 1.6%–99.8 ± 4.9%) and thickness (19.6 ± 1.9–170.8 ± 11.5 μm), storage stability characteristics, and % residual humidity (<3%), as well as favourable swelling and mucoadhesive properties. Response surface methodology determined the optimum composition for flexible nasal film with maximized DH permeation. All selected factors interacted with each other and the effect of these interactions on responses is strongly related to the factor’s concentration ratios. Based on these encouraging results, in vivo serum and brain pharmacokinetic study of the optimized nasal film, in comparison to DH oral administration, is ongoing in an animal model. Full article

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. Full article