Formulation of Polymeric Micelles to Increase the Solubility and Photostability of Caffeic Acid.

Caffeic acid (CA), a hydrophobic polyphenol with various pharmacological activities, exhibits a low aqueous solubility and sensitivity to light. In order to improve its chemical properties and overcome the limits in its application, the compound was loaded in P123 micelles (MCs) prepared using two polymer concentrations (10 and 20% /, MC10 and MC20). The micelles were characterised in terms of the size distribution, zeta potential, drug encapsulation efficiency, rheology, and cumulative drug release.

Multivariate Approaches in Quantitative Structure-Property Relationships Study for the Photostability Assessment of 1,4-Dihydropyridine Derivatives.

1,4-dihydropyridines (1,4-DHPs) are widely recognized as highly effective L-type calcium channel blockers with significant therapeutic benefits in the treatment of cardiovascular disorders. 1,4-DHPs can also target T-type calcium channels, making them promising drug candidates for neurological conditions. When exposed to light, all 1,4-DHPs tend to easily degrade, leading to an oxidation product derived from the aromatization of the dihydropyridine ring.

Dissecting CYP1A2 Activation by Arylalkanoic Acid Prodrugs toward the Development of Anti-Inflammatory Agents.

Arylalkane-derived prodrugs of arylacetic acids are a small group of substances that have long been known for their anti-inflammatory action. Despite their ease of synthesis and good potential for the development of new potent and safe anti-inflammatory agents, this group of substances has not received much attention from researchers so far. Therefore, representative arylalkane derivatives were investigated through molecular docking techniques to verify the possible hepatic activation mode toward active metabolites by CYP1A2.

Multivariate Curve Resolution Methodology Applied to the ATR-FTIR Data for Adulteration Assessment of Virgin Coconut Oil.

Virgin coconut oil (VCO) is a functional food with important health benefits. Its economic interest encourages fraudsters to deliberately adulterate VCO with cheap and low-quality vegetable oils for financial gain, causing health and safety problems for consumers. In this context, there is an urgent need for rapid, accurate, and precise analytical techniques to detect VCO adulteration.

Wine Lees as Source of Antioxidant Molecules: Green Extraction Procedure and Biological Activity.

An ultrasound-assisted extraction method, employing ethanol and water as solvents at low temperature (30 °C) and reduced time (15 min), was proposed to extract bioactive molecules from different cultivars (, , , and ) of wine lees. All the extract yields were evaluated and their contents of phenolic acids, flavonoids, and total polyphenols were determined by means of colorimetric assays and high-performance liquid chromatography coupled with diode-array detection (HPLC-DAD) and Fourier transform infrared (FTIR) techniques. Radical scavenging assays were performed and the extracted with a hydroalcoholic mixture returned the best results both against ABTS (0.

Recent advances in PI3K/PKB/mTOR inhibitors as new anticancer agents.

The biochemical role of the PI3K/PKB/mTOR signalling pathway in cell-cycle regulation is now well known. During the onset and development of different forms of cancer it becomes overactive reducing apoptosis and allowing cell proliferation. Therefore, this pathway has become an important target for the treatment of various forms of malignant tumors, including breast cancer and follicular lymphoma.

Anticancer Drugs: Recent Strategies to Improve Stability Profile, Pharmacokinetic and Pharmacodynamic Properties.

In past decades, anticancer research has led to remarkable results despite many of the approved drugs still being characterized by high systemic toxicity mainly due to the lack of tumor selectivity and present pharmacokinetic drawbacks, including low water solubility, that negatively affect the drug circulation time and bioavailability. The stability studies, performed in mild conditions during their development or under stressing exposure to high temperature, hydrolytic medium or light source, have demonstrated the sensitivity of anticancer drugs to many parameters. For this reason, the formation of degradation products is assessed both in pharmaceutical formulations and in the environment as hospital waste.

Interaction of letrozole and its degradation products with aromatase: chemometric assessment of kinetics and structure-based binding validation.

Letrozole is one of the most prescribed drugs for the treatment of breast cancer in post-menopausal women, and it is endowed with selective peripheral aromatase inhibitory activity. The efficacy of this drug is also a consequence of its long-lasting activity, likely due to its metabolic stability. The reactivity of cyano groups in the letrozole structure could, however, lead to chemical derivatives still endowed with residual biological activity.

Photodegradation of Anti-Inflammatory Drugs: Stability Tests and Lipid Nanocarriers for Their Photoprotection.

The present paper provides an updated overview of the methodologies applied in photodegradation studies of non-steroidal anti-inflammatory drugs. Photostability tests, performed according to international standards, have clearly demonstrated the photolability of many drugs belonging to this class, observed during the preparation of commercial forms, administration or when dispersed in the environment. The photodegradation profile of these drugs is usually monitored by spectrophotometric or chromatographic techniques and in many studies the analytical data are processed by chemometric procedures.

Polyphenols from Citrus Tacle Extract Endowed with HMGCR Inhibitory Activity: An Antihypercholesterolemia Natural Remedy.

Tacle is a citrus fruit obtained from the crossbreeding of Clementine and Tarocco cultivars. This fruit retains a promising nutraceutical potential most likely due to a high content in polyphenols, among which the main constituents are the two glycosides naringin and hesperidin. Herein, we evaluated, through an in vitro assay, the capability of Tacle extracts to inhibit the hydroxymethylglutaryl-CoA reductase enzyme, which plays a key role in cholesterol biosynthesis.

Central retinal thickness fluctuations in patients treated with anti-VEGF for neovascular age related macular degeneration.

Purpose: This is a retrospective, single-center, non randomized interventional real life study, investigating the correlation between variability of central retinal thickness (CRT) and functional outcomes during 2 years of anti-VEGF therapy in patients treated for neovascular age related macular degeneration (nAMD).

Background: CRT fluctuations can depend on various factors such as the correct timing of injections, the therapeutic algorithm, and the number of injections (NI) performed; it is important to understand if CRT fluctuations are responsible for worse visual outcomes and consequently to identify the correct ways to avoid or reduce them.

Methods: Forty-one patients were treated for nAMD with aflibercept: 0.

Toward Multitasking Pharmacological COX-Targeting Agents: Non-Steroidal Anti-Inflammatory Prodrugs with Antiproliferative Effects.

The antitumor activity of certain anti-inflammatory drugs is often attributed to an indirect effect based on the inhibition of COX enzymes. In the case of anti-inflammatory prodrugs, this property could be attributed to the parent molecules with mechanism other than COX inhibition, particularly through formulations capable of slowing down their metabolic conversion. In this work, a pilot docking study aimed at comparing the interaction of two prodrugs, nabumetone (NB) and its tricyclic analog 7-methoxy-2,3-dihydro-1-cyclopenta[]naphthalen-1-one (MC), and their common active metabolite 6-methoxy-2-naphthylacetic acid (MNA) with the COX binding site, was carried out.

Use of Pluronic Surfactants in Gel Formulations of Photosensitive 1,4-Dihydropyridine Derivatives: A Potential Approach in the Treatment of Neuropathic Pain.

1,4-Dihydropyridines (DHPs) are the most important class of L-type calcium channel blockers that are employed for the treatment of cardiovascular diseases, particularly hypertension. Various modifications on this scaffold lead to the discovery of new DHPs blocking different types of calcium channels. Among them, the T-type calcium channel has recently attracted great interest due to its role in chronic pain conditions.

Photostability study of multicomponent drug formulations via MCR-ALS: The case of the hydrochlorothiazide-amiloride mixture.

The kinetics and photodegradation mechanism of the pharmaceutical mixture of hydrochlorothiazide (HCT) and amiloride (AML) has been studied in depth using a chemometric approach. Water solutions of HCT and AML, separately or in binary mixtures, were irradiated with forced light at different pH values (3, 7, 9 and 12). Multivariate Curve Resolution - Alternating Least Squares (MCR-ALS) modelling has been applied to the experimental data recorded by UV spectrophotometry and HPLC-UV/MS.

Gel Formulation of Nabumetone and a Newly Synthesized Analog: Microemulsion as a Photoprotective Topical Delivery System.

Photostability studies were performed on topical formulations containing the anti-inflammatory drug Nabumetone and an analog newly synthesized in order to achieve better photostability and pharmacokinetic profile. Stability tests, according to the International Conference on Harmonization rules, were applied on ethanol solutions and topical gel formulations of both compounds. The photodegradation profiles were monitored by Multivariate curve resolution applied to the UV spectral data.

Evaluation of human breastmilk adulteration by combining Fourier transform infrared spectroscopy and partial least square modeling.

A two-step chemometric procedure was developed on the attenuated total reflection-Fourier transform infrared data of human breastmilk to detect adulteration by water or cow milk. The samples, collected from a Milk Bank, were analyzed before and after adulteration with whole, skimmed, semi-skimmed cow milk and water. A preliminary clustering via principal component analysis distinguished three classes: pure milk, milk adulterated with water, and milk adulterated with cow milk.

Reverse Transcriptase Inhibitors Nanosystems Designed for Drug Stability and Controlled Delivery.

An in-depth analysis of nanotechnology applications for the improvement of solubility, distribution, bioavailability and stability of reverse transcriptase inhibitors is reported. Current clinically used nucleoside and non-nucleoside agents, included in combination therapies, were examined in the present survey, as drugs belonging to these classes are the major component of highly active antiretroviral treatments. The inclusion of such agents into supramolecular vesicular systems, such as liposomes, niosomes and lipid solid NPs, overcomes several drawbacks related to the action of these drugs, including drug instability and unfavorable pharmacokinetics.

Photo and thermal stress of linseed oil and stabilization strategies.

The thermal and light stability of linseed oil has been studied by monitoring the concentrations of fatty acids and lignans, as main nutraceutical components. Linseed oil was subjected to stressing light and temperature conditions, in accordance with the ICH international rules, and monitored by UV-vis spectroscopy and HPLC-DAD. The change of UV spectra along the photodegradation tests, setting the irradiation power at 350 W/m, confirmed a significant overall sensitivity of linseed oil to light.

1,4-Dihydropyridine Antihypertensive Drugs: Recent Advances in Photostabilization Strategies.

The 1,4-dihydropyridine (DHP) drugs are nowadays the most used drugs in the treatment of hypertension. However, all the structures in this series present a significant sensitivity to light, leading to the complete loss of pharmacological activity. This degradation is particularly evident in aqueous solution, so much so that almost all DHP drugs on the market are formulated in solid preparations, especially tablets.

CCR5/CXCR4 Dual Antagonism for the Improvement of HIV Infection Therapy.

HIV entry in the host cell requires the interaction with the CD4 membrane receptor, and depends on the activation of one or both co-receptors CCR5 and CXCR4. Former selective co-receptor antagonists, acting at early stages of infection, are able to impair the receptor functions, preventing the viral spread toward AIDS. Due to the capability of HIV to develop resistance by switching from CCR5 to CXCR4, dual co-receptor antagonists could represent the next generation of AIDS prophylaxis drugs.

A New Generation of Dihydropyridine Calcium Channel Blockers: Photostabilization of Liquid Formulations Using Nonionic Surfactants.

The stability profile of a new 1,4-dihydropyridine derivative (DHP), representative of a series with a hexahydroquinoline ring, was studied to design light-stable liquid formulations. This molecule, named M3, has been shown among the analogs to have a high capacity to block both L- and T-type calcium channels. The ethanol solution of the drug was subjected to a photodegradation test, in accordance with standard rules.

Identification by Molecular Docking ofHomoisoflavones from Leopoldia comosa as Ligands of Estrogen Receptors.

The physiological responses to estrogen hormones are mediated within specific tissues by at least two distinct receptors, ER and ER. Several natural and synthetic molecules show activity by interacting with these proteins. In particular, a number of vegetal compounds known as phytoestrogens shows estrogenic or anti-estrogenic activity.

Benzopyrroloxazines containing a bridgehead nitrogen atom as promising scaffolds for the achievement of biologically active agents.

The present review lists the papers and patents dealing with the class of polycondensed heterocycles called benzopyrroloxazines published in the last decades. The survey is limited to substances characterized by the presence of a bridgehead N atom, which means that the present N atom serves to connect different rings within the same molecule. In the case of benzopyrroloxazines, the bridgehead N atom belongs at the same time to the pyrrole and oxazine rings.

Photosensitive drugs: a review on their photoprotection by liposomes and cyclodextrins.

Nowadays, an exciting challenge in the drug chemistry and technology research is represented by the development of methods aimed to protect molecular integrity and therapeutic activity of drugs from effects of light. The photostability characterization is ruled by ICH (The International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use), which releases details throughout basic protocols of stability tests to be performed on new medicinal products for human use. The definition of suitable photoprotective systems is fundamental for pharmaceutical manufacturing and for human healthy as well, since light exposure may affect either drugs or drug formulations giving rise even to allergenic or mutagenic by-products.

Light-sensitive drugs in topical formulations: stability indicating methods and photostabilization strategies.

Photostability tests applied on commercial specialties for topical use have demonstrated a greater vulnerability of several drugs, due to greater exposure to light than other pharmaceutical forms. Photodegradation of a drug can considerably modify its pharmacokinetic behavior by varying the therapeutic index. The evaluation of the degradation profile of a drug, according to the ICH rules, is of primary importance in developing an appropriate topical formulation.