Gallic Acid-Based Hydrogels for Phloretin Intestinal Release: A Promising Strategy to Reduce Oxidative Stress in Chronic Diabetes.

Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia caused by abnormalities in insulin secretion and/or action. In patients with diabetes, complications such as blindness, delayed wound healing, erectile dysfunction, renal failure, heart disease, etc., are generally related to an increase in ROS levels which, when activated, trigger hyperglycemia-induced lesions, inflammation and insulin resistance. In fact, extensive cell damage and death occurs mainly due to the effect that ROS exerts at the level of cellular constituents, causing the deterioration of DNA and peroxidation of proteins and lipids. Furthermore, elevated levels of reactive oxygen species (ROS) and an imbalance of redox levels in diabetic patients produce insulin resistance. These destructive effects can be controlled by the defense network of antioxidants of natural origin such as phloretin and gallic acid. For this reason, the objective of this work was to create a nanocarrier (hydrogel) based on gallic acid containing phloretin to increase the antioxidant effect of the two substances which function as fundamental for reducing the mechanisms linked to oxidative stress in patients suffering from chronic diabetes. Furthermore, since the bioavailability problems of phloretin at the intestinal level are known, this carrier could facilitate its release and absorption. The obtained hydrogel was characterized using Fourier transform infrared spectroscopy (FT-IR). Its degree of swelling (a%) and phloretin release were tested under pH conditions simulating the gastric and intestinal environment (1.2, 6.8 and 7.4). The antioxidant activity, inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a free radical source, was evaluated for four hours. All results showed that gallate hydrogel could be applied for releasing intestinal phloretin and reducing the ROS levels.

Hemostatic gauze based on chitosan and hydroquinone: preparation, characterization and blood coagulation evaluation.

This work concerns on the preparation and performance evaluation of a new chitosan hydroquinone based gauze for hemostatic use. Chitosan and hydroquinone were firstly connected by etherification and then linked to the pre-carboxylate gauze. The functionalized material and the chitosan-hydroquinone ether were characterized by Fourier Transform Infrared (FT-IR) Spectroscopy and Differential Scanning Calorimetry (DSC). FT-IR results showed that an esterification occurred on carboxylic group of the gauze. The gauze functionalization degree was also evaluated by volumetric analysis. The ether hydroquinone content was obtained by the Folin test. Moreover, the linkage between hydroquinone and chitosan was confirmed by nuclear magnetic resonance (NMR). The hemostatic activity of functionalized gauze was evaluated by dynamic blood clotting assays. The obtained results showed that the prepared material can shorten the blood clotting time and induce the adhesion and activation of platelets. Finally, swelling characteristic of the new gauze was evaluated to confirm its high capacity to absorb the blood.

α-Tocopheryl linolenate solid lipid nanoparticles for the encapsulation, protection, and release of the omega-3 polyunsaturated fatty acid: in vitro anti-melanoma activity evaluation.

The main target of this study was the preparation, characterization and antioxidant activity evaluation of α-tocopheryl linolenate based solid lipid nanoparticles (SLNs-TL), able to incorporate omega-3 α-linolenic acid, useful for the treatment of melanoma, a type of skin cancer. In particular, α-linolenic acid was successfully derivatized with α-tocopherol and the obtained compound was characterized by Fourier transform infrared (FT-IR) and by 1H NMR to confirm the ester linkage. Both the empty SLNs-TL that SLNs-TL-LIN, containing omega-3-linolenic acid, were prepared through the technique of the microemulsion. The nanoparticles were characterized for entrapment efficiency, size and shape. Their antioxidant activity was investigated in rat liver microsomal membranes in inhibiting the lipid peroxidation induced by tert-butyl hydroperoxide (tert-BOOH), which endogenously produces alkoxyl radicals by Fenton reactions. The obtained results indicate that the α-tocopherol, linked by ester bond to α-linolenic acid, maintains an excellent antioxidant activity. The encapsulation efficiency was equal to 77% and the polydispersity index 0.198 indicating a good dimensional distribution. Furthermore, the nanoparticles were tested in vitro for their cytotoxic activity against human melanoma cancer cell line C32. Both empty SLNs-TL and loaded SLNs-TL-LIN showed a high biological activity, being more effective than α-linolenic acid and α-tocopherol. The results indicated that these nanoparticles could provide the delivery and the protection of unstable molecules, such as α-linolenic acid, from degradation induced by mechanisms of oxidative stress.

Solid lipid nanoparticles for antifungal drugs delivery for topical applications.

Systemic and local infections caused by fungi, in particular those concerning the skin and nails, are increasing. Various drugs are used for mycoses treatment such as amphotericin B, nystatin and ketoconazole, fluconazole, itraconazole and fluconazole, among others. Unfortunately, many of these antifungal agents can cause side effects such as allergic and severe skin reaction. With the aim to reduce these side effects and maximize the antifungal drug activity, various drug-delivery systems have been formulated and been investigated in the last few years. In this context, solid lipid nanoparticles are attracting great attention. The aim of this review is to highlight the role of solid lipid nanoparticles as carriers of antifungal drugs for topical applications.

Novel microspheres based on triterpene saponins from the roots of Physospermum verticillatum (Waldst & Kit) (Apiaceae) for the improvement of gemcitabine release.

OBJECTIVES: This study concerns the preparation and characterization of microspheres based on a mixture of triterpene saponins, from Physospermum verticillatum (Waldst & Kit), as a carrier for the specific release of gemcitabine. METHODS: Triterpene saponins were derivatized with acrylic acid. The obtained polymerizable product was characterized by Fourier transform infrared to confirm the ester linkage. Then, spherical microparticles were prepared by suspension radical copolymerization and impregnated with gemcitabine. KEY FINDINGS: Microspheres exhibited a mean diameter of 2.7 µ. The swelling studies showed that particles swell most at pH 6.2, typical of the tumour pathology, than at pH 7.4, miming physiological conditions. The microspheres were loaded with gemcitabine (LE 72.2%). Their release profile showed an initial dot of around 24% and a further release for 24 h. CONCLUSIONS: This carrier could be potentially release the drug in the lung, as a function of different pHs between tumour cells and healthy, reducing the systemic drug toxicity, allowing the reduction of the doses number, increasing the drug half-life and eliminating the problems related to the fast clearance of gemcitabine administration.