1,720,971 research outputs found
Formulation for low bioavailability substances containing a n-acetylcysteine-chitosan salt
No full textDevelopment and preclinical testing of advanced formulations containing t-resveratrol and coenzyme Q10 with increased oral bioaccessibility and bioavailability
No full textThe effectiveness of nutraceutical products is often hindered by reduced intestinal bioaccessibility and even more limited bioavailability. The reasons for this phenomenon primarily lie in the presence of plant extracts containing a phyto-complex composed of substances with low or even negligible water solubility. Additionally, there are non-plant-derived substances with lipophilic characteristics and molecular sizes that do not ensure rapid dispersion in duodenal fluids. These conditions of limited bioaccessibility are further complicated by strict regulations governing nutraceutical products composition that limit the use of excipients that could improve the solubility of these substances. Consequently, a technological approach that promotes both the aqueous dispersion of active ingredients and the reduction of pre-systemic metabolism, as well as lymphatic access, represents the most promising and viable horizon. An equally important element to consider in ensuring the effectiveness of nutraceuticals is the protection of active ingredients from the gastric environment, which, due to its pH conditions and the presence of enzymes and mucins, potentially complicates the stability and bioaccessibility of many active ingredients. Two substances in the nutraceutical sector that are paradigmatic for their poor bioaccessibility and bioavailability, even though having high pharmacological and therapeutic potential, are Coenzyme Q10 (CoQ10) and Resveratrol (RES). The former is an isoprenoid quinone that is a component of the mitochondrial respiratory chain in eukaryotic cells, playing the crucial role of electron transporter in the biochemical process that leads to ATP synthesis. The latter is a polyphenolic stilbene extracted from various plant species, particularly from the seeds and skin of Vitis vinifera and the roots of Polygonum cuspidatum, possessing estrogen-agonistic, anti-neoplastic, and cardiovascular protective properties. From this perspective, the design and testing of new technological systems such as self-emulsifying drug delivery systems (SEDDS, SNEDDS) and the more recent lipid-based self-emulsifying drug delivery systems (LiBADDS) represent the new frontier for the delivery of substances with low solubility and reduced molecular weight (small molecules). This is especially true given their potential to enhance bioaccessibility while also facilitating their targeting into the lymphatic circulation, following incorporation into lipoproteins.
In this work, new lipid-based and proteo-lipid-based self-emulsifying systems were designed and developed to maximize the bioaccessibility of RES and CoQ10, starting from the unique molecular and physicochemical characteristics of the two substances and their pharmacokinetic and biotransformation pathways. Specifically, for RES sodium caseinate (NaC) was chosen as a protein capable of ensuring gastric resistance and intestinal micellar delivery of RES after activation by pancreatic enzymes. NaC demonstrated its ability to ensure the gastric resistance of the formulations even in the presence of pepsin and simulated human gastric fluid (FaSSGF), in addition to exhibiting unusual characteristics of modulability in intestinal delivery. This agent was shown to provide release times that are directly proportional to its content in the tablet and inversely proportional when combined with non-ionic emulsifying excipients. Furthermore, the presence of NaC contributes to the formation of mixed micelles in the intestine in combination with bile salts and the mono- and diglycerides of fatty acids, thereby ensuring the formation of dispersions with reduced micellar diameters on the nanometer scale
Nutraceutical Approaches to Dyslipidaemia: The Main Formulative Issues Preventing Efficacy
Full text linkCurrently, the nutraceutical approach to treat dyslipidaemia is increasing in use, and in many cases is used by physicians as the first choice in the treatment of patients with borderline values. Nutraceuticals represent an excellent opportunity to treat the preliminary conditions not yet showing the pathological signs of dyslipidaemia. Their general safety, the patient’s confidence, the convincing proof of efficacy and the reasonable costs prompted the market of new preparations. Despite this premise, many nutraceutical products are poorly formulated and do not meet the minimum requirements to ensure efficacy in normalizing blood lipid profiles, promoting cardiovascular protection, and normalizing disorders of glycemic metabolism. In this context, bioaccessibility and bioavailability of the active compounds is a crucial issue. Little attention is paid to the proper formulations needed to improve the overall bioavailability of the active molecules. According to these data, many products prove to be insufficient to ensure full enteric absorption. The present review analysed the literature in the field of nutraceuticals for the treatment of dyslipidemia, focusing on resveratrol, red yeast rice, berberine, and plant sterols, which are among the nutraceuticals with the greatest formulation problems, highlighting bioavailability and the most suitable formulations
Sublingual Delivery of Astaxanthin through a Novel Ascorbyl Palmitate-Based Nanoemulsion: Preliminary Data
Full text linkAstaxanthin is a carotenoid extracted from several seaweeds with ascertained therapeutic activity. With specific reference, astaxanthin is widely used in clinical practice to improve ocular tissue health and skin protection from UV ray damages. Despite its well-documented pleiotropic actions and demonstrated clinical efficacy, its bioavailability in humans is low and limited because of its hydrophobicity and poor dissolution in enteric fluids. Furthermore, astaxanthin is very unstable molecule and very sensitive to light exposure and thermal stress. Taken together, these pharmacological and chemical-physical features strongly limit pharmaceutical and nutraceutical development of astaxanthin-based products and as a consequence its full clinical usage. This work describes the preliminary in vitro investigation of sublingual absorption of astaxanthin through a novel ascorbyl palmitate (ASP) based nanoemulsion
Self-nanoemulsifying system in the accumulation of resveratrol and N-acetylcysteine in the epidermis and dermis
Full text linkTrans-resveratrol (RES) and N-acetylcysteine (NAC) have protective effects on biological processes; therefore, they are frequently included in food supplements. Their possible applications for the prevention of free radical-induced damage to the skin are of particular physiological relevance; however, their usefulness is limited by their metabolic fate and the unpredictability of their delivery to the skin following oral administration. In this work, we evaluated the concomitant and direct application of RES and NAC on the skin using a self-nanoemulsifying system we previously developed for the oral delivery of poorly absorbed food supplements. We evaluated the capability of this system to increase RES and NAC accumulation in porcine skin using permeation studies in Franz diffusion cells. The ascorbyl palmitate (ASP) self-nanoemulsifying system considerably increased RES and NAC accumulation in the epidermis and dermis, which peaked 6 h after application. This study reveals a new formulation strategy to improve the bioavailability of ingredients, which was previously used in the health supplements field, but has rarely been employed in dermatology because of its poor distribution in the skin
Effectiveness and Safety of Novel Nutraceutical Formulation Added to Ezetimibe in Statin-Intolerant Hypercholesterolemic Subjects with Moderate-to-High Cardiovascular Risk
No full textThe effectiveness of statins in the primary and secondary prevention of cardiovascular (CV) diseases has been widely proven. However, the onset of adverse events associated with their use prevents to achieve the therapeutic targets recommended by the guidelines (GL) for the management of dyslipidemia. In the event of statin intolerance, the GL recommend to use bile acid sequestrants, fibrates, and ezetimibe in monotherapy, but their benefits in improving lipid pattern are quite modest. This study aims at evaluating the effectiveness and safety of a nutraceutical compound (NC) associated with ezetimibe (EZE) on the lipid profile in statin-intolerant patients with moderate-to-high CV risk. Ninety-six statin-intolerant hypertensive and hypercholesterolemic subjects treated pharmacologically with EZE 10 mg daily were randomized in open label (n = 48) to take for 3 months a NC containing Monacolin-K (MK), Berberine Hydrochloride (BC), t-Resveratrol (RES), Quercetin (QUER), and Chromium (CH) in the form of a gastro-resistant tablet that improves enteric bioaccessibility and bioavailability of these substances. The control group (n = 48) took only EZE in monotherapy at the same dosage; both groups followed a standardized lipid-lowering diet. The total serum cholesterol (TC), low density lipoprotein cholesterol (LDLC), high density lipoprotein cholesterol (HDLC), triglycerides (TG), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and creatinine phosphokinase (CPK) levels were compared at the follow-up in both groups using Student's t-test. TC and LDL levels reduced in both groups, but were lower in the group treated with EZE + NC (-25.9% vs. -15%, P < .05 and -38.7% vs. -21.0%, P < .05, respectively). No changes were observed in either group regarding a decrease in TG (-9.4% vs. -11.7%, NS) and an increase in HDLC (+4.2% vs. +1.1%, NS). The AST, ALT, and CPK levels increased in the group treated with the EZE + NC compared to the control group, but were still within the acceptable range. There was no difference concerning the lipid-lowering treatment between gender, and no patient withdrew from the study. In the short term, the EZE + NC combination therapy is well tolerated and effective in improving TC and LDLC levels in statin-intolerant patients with moderate-to-high CV risk
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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