Roberta Cassano

Stearyl ferulate-based solid lipid nanoparticles for the encapsulation and stabilization of β-carotene and α-tocopherol

UVA exposure induces DNA damage that could result in skin carcinogenesis. Antioxidants are usually employed as protective agents to avoid this problem: in particular, both beta-carotene and alpha-tocopherol can protect the skin against UVA-induced damage. It is well known that the photochemical instability of these compounds has been a limiting factor for their applications to protect skin. In this study, stearyl ferulate-based solid lipid nanoparticles (SF-SLNs), as vehicles for beta-carotene and alpha-tocopherol, were formulated to improve the stability of these compounds. The SF-SLNs were characterized for entrapment efficiency, size and shape together with their cytotoxicity and capability to inhibit lipid peroxidation. After treatment with a pro-oxidant and/or exposition to sunlight the antioxidants entrapped in SF-SLNs were extremely stable. The results highlighted how SF-SLNs represent a suitable vehicle for beta-carotene and alpha-tocopherol stabilizing and protecting them from degradation. A dermatological formulation in order to prevent skin damages is, therefore, suggested.

A novel dextran hydrogel linking trans-ferulic acid for the stabilization and transdermal delivery of vitamin E

Long-term exposure of the skin to UV light causes degenerative effects, which can be minimized by using antioxidant formulations. The major challenge in this regard is that a significant amount of antioxidant should reach at the site for effective photoprotection. However, barrier properties of the skin limit their use. In the present study, vitamin E (alpha-tocopherol) was loaded into a dextran hydrogel containing ferulic moieties, covalently linked, to improve its topical delivery, and also to increase its relative poor stability, which is due to direct exposure to UV light. Methacrylic groups were first introduced onto the dextran polymer backbones, then the obtained methacrylated dextran was copolymerized with aminoethyl methacrylate, and subsequently esterificated with trans-ferulic acid. The new biopolymer was characterized by Fourier transform infrared spectroscopy. The values of content of phenolic groups were determined. Its ability in inhibiting lipid peroxidation in rat liver microsomal membranes induced in vitro by a source of free radicals, that is tert-butyl hydroperoxide, was studied. Hydrogel was also characterized for swelling behaviour, vitamin E loading efficiency, release, and deposition on the rabbit skin. Additionally, vitamin E deposition was compared through hydrogels, respectively, containing and not containing trans-ferulic acid. The results showed that ferulate hydrogel was a more effective carrier in protecting vitamin E from photodegradation than hydrogel without antioxidant moieties. Then antioxidant hydrogel could be of potential use for cosmetic and pharmaceutical purposes as carrier of vitamin E that is an antioxidant that reduces erythema, photoaging, photocarcinogenesis, edema, and skin hypersensitivity associated with exposure to ultraviolet B (UVB) radiation, because of its protective effects.

Characterization of the S-denitrosylating activity of bilirubin.

Bilirubin‐IX‐α (BR) is an endogenous molecule with a strong antioxidant feature due to its ability to scavenge free radicals. In this paper, we demonstrated that BR, at concentrations close to those found within the cell (0.1–2.5 μM), acted as a denitrosylating agent and increased the release of nitric oxide from S‐nitrosoglutathione (GSNO) and S‐nitrosocysteine (SNOC) (2.5 μM). The complexation of BR with saturating concentrations of human serum albumin (HSA, 2.5 μM) did not further increase nitric oxide release from GSNO and SNOC. At concentrations similar to those reached in plasma (5–20 μM), BR denitrosylated S‐nitroso‐HSA (2.5 μM), the main circulating S‐nitrosothiol, and this effect was potentiated by the complexation of BR with saturating HSA (20 μM). Furthermore, the product(s) of the reaction between nitric oxide and BR were identified. Ultraviolet and mass spectrometry analysis revealed that nitric oxide binds to BR forming a N‐nitroso derivative (BR–nitric oxide) with extinction coefficients of 1.393 mM−1cm−1 and 2.254 mM−1cm−1 in methanol and NaOH, respectively. The formation of BR–nitric oxide did not occur only in a reconstituted system, but was confirmed in rat fibroblasts exposed to pro‐oxidant stimuli. These results provided novel insights on the antioxidant characteristic of BR through its interaction with nitric oxide, a gaseous neurotransmitter with a well‐known dual effect, namely neuroprotective under physiological conditions or neurotoxic if produced in excess, and proposed BR–nitric oxide as a new biomarker of oxidative/nitrosative stress.

Trans-ferulic acid-based solid lipid nanoparticles and their antioxidant effect in rat brain microsomes

In this study, stearic acid- and stearyl ferulate-based solid lipid nanoparticles containing trans-ferulic acid (SLN-FA and SLN-SF-FA, respectively), were prepared and characterized for loading efficiency, size and shape. In addition, by using rat brain microsomes, we evaluated in vitro the antioxidant activity of these formulations against three well known initiators of lipid peroxidation, such as AAPH, NADPH/ADP-Fe(3+) and SIN-1 which in turn generate the peroxyl and perferryl radicals as well as peroxynitrite, respectively. Commercially available FA and its ethyl ester (FAEE) were used as comparators. Both SLN-FA and SLN-SF-FA dose-dependently reduced lipid peroxidation induced by the three oxidants. Interestingly, SLN-SF-FA displayed greater efficacy (EC50) and potency (maximal activity) against AAPH- and NADPH/ADP-Fe(3+)-induced lipid peroxidation. Our results support the idea that this new formulations could facilitate the uptake of FA by the cells because of their lipophilic structure, thus increasing FA bioavailability. Furthermore, stearyl ferulate-based nanoparticles could prevent the degradation of FA entrapped on their structure, making FA almost entirely available to explicate its antioxidant power once released.

Effect of formulations variables on the in vitro percutaneous permeation of Sodium Diclofenac from new vesicular systems obtained from Pluronic triblock copolymers

The objectives of our study were to evaluate the ability of Pluronic L64 surfactant to give niosomal systems alone or after its functionalization with acrylic groups. The achieved formulations were tested for the percutaneous permeation of Sodium Diclofenac as model drug. In vitro experiments were conducted by Franz diffusion cells, using rabbit ear skin. Data recorded over 24h were compared with those obtained from the drug solution, as control. In addition, the stability of niosomes was improved polymerizing the acryloyl groups of the monomers, because, as reported in the literature, polymerized vesicles maintain their shape for long periods of time, and show remarkable increase in drug encapsulation efficiency. Mean vesicles diameter, drug entrapment efficiency, percutaneous permeation and release profiles were investigated for all vesicles with different composition. The results indicated an increase in mean vesicles diameter and entrapment efficiency with the increase of polymerizable moieties amount. These properties were found to be more evident when the vesicles were polymerized. In addition cytotoxic effects were estimated. The results of this study showed that niosomes based on commercial, functionalized or a mixture of both Pluronic L64 surfactants can be used to achieve retarded release and to enhance the permeation of Sodium Diclofenac, without incurring unacceptable toxicity.

Niosomes from α,ω-trioxyethylene-bis(sodium 2-dodecyloxy-propylenesulfonate): Preparation and characterization

The synthesis and characterisation of new surfactants with peculiar physical-chemical properties are amongst the most promising and expanding issues in pharmacological colloid science. The most used vesicular carriers are liposomes prepared from a wide variety of natural and synthetic phospholipids, but several ionic and non-ionic amphiphiles have been used to form multilamellar and/or unilamellar vesicles. In the present study the synthesis of alpha,omega-trioxyethylene-bis(sodium 2-dodecyloxy-propylenesulfonate), an anionic Gemini surfactant, and its ability to form niosomes are elucidated. The compound forms vesicles with and without added cholesterol. The vesicular systems were characterized by size, shape and drug entrapment efficiency. The compounds to be incorporated are beta-carotene and ferulic acid, as antioxidants, acetyl salicylic acid, as FANS, and the antineoplastic 5-flurouracil, widely used in dermatological disorders. The results of this study show that alpha,omega-trioxyethylene-bis(sodium 2-dodecyloxy-propylenesulfonate) can be used for the preparation of niosomes entrapping lypophilic, amphiphilic or hydrophilic substances. These niosomes may be promising candidates as percutaneous carriers for the aforementioned drugs.

New sucrose cocoate based vesicles: Preparation characterization and skin permeation studies

A commercial sucrose cocoate surfactant was used to obtain a new vesicular system for transdermal drug delivery. The preparation, the dimensional and morphological characterizations and the skin permeation profile of these new niosomes were evaluated. Moreover we studied the possible employment of mixture of sucrose cocoate and cholesterol at different weigh ratios for the vesicles preparation and we analyzed the influence of cholesterol on niosomes properties. Diclofenac and Sulfadiazine were used as model drugs. Results suggest that sucrose cocoate was able to form vesicles in the presence or not of cholesterol and the addition of cholesterol leads to a variation of size: larger vesicles were obtained in the absence of cholesterol both in empty and drug-loaded niosomes. All vesicles were spherical and regular in shape. In vitro skin permeation profiles were significantly higher than the free drug solution, indicating the favourable relations between skin and niosomes. The faster release of the drug was found for niosomes with no cholesterol or with a reduced amount of this membrane additive, in particular the optimal formulation was that in which the cholesterol content was about 27 wt% of total lipid amount: probably this value is a good compromise between the membrane stability and its deformation capacity, allowing a higher drug permeation across the skin.

Isoniazid-gelatin conjugate microparticles containing rifampicin for the treatment of tuberculosis

In this work, a new polymeric microparticle system based on gelatin covalently bound to isoniazid (ISN) and containing rifampicin (RFP) was prepared by spray‐drying technique. Microparticle aptitude to nebulisation and their capability of interacting with A549, alveolar basal epithelial cells, were evaluated in vitro.

Respirable rifampicin-based microspheres containing isoniazid for tuberculosis treatment

The purpose of this investigation was to develop small microspheres for delivering antimycobacterial drugs to infected host macrophages. Rifampicin-based microparticles were prepared. The drug was covalently linked to acrylic moieties to obtain a polymerizable derivative for the preparation of materials useful as drug delivery systems that then were loaded with isoniazid acting in synergy with rifampicin. Their antitubercular activity was determined in vitro. Fourier transform infrared spectroscopy confirmed hydrogel structure. Morphological analysis showed microparticles with spherical shape and homogeneous surface. In vitro release studies were performed in media simulating physiologic pH (7.4) and endosomal of alveolar macrophages pH (5.2). A similar amount of isoniazid was delivered within the first 6 h at both pHs, while a smaller amount of the drug was delivered at pH 7.4 in the last phase of the study. In vitro antitubercular activity showed a behavior comparable to that of rifampicin and isoniazid free. Bioactive swelling matrices, showing a high swelling degree into a medium miming intra alveolar environment, were obtained. They could be applied for their antitubercular activity.

Preparation, characterization and in vitro activities evaluation of solid lipid nanoparticles based on PEG-40 stearate for antifungal drugs vaginal delivery

Abstract The present article reports the preparation, characterization and performance evaluation of solid lipid nanoparticles (SLNs) based on polyoxyethylene-40 stearate (PEG-40 stearate) for the administration of antifungal agents such as ketoconazole and clotrimazole. These nanoparticles could be useful in the treatment of vaginal infections sustained by Candida albicans. In particular, PEG-40 stearate was made to react with acryloyl chloride in order to introduce an easily polymerizable moiety for the creation of a second shell and to ensure a slow drug release. In addition, the differences on the release profiles between PEG-40 stearate-based nanoparticles, PEG-40 stearate acrylate based and polymerized ones, were analyzed under conditions, simulating the typical environment of Candida albicans infection. Then, the antifungal activity of nanoparticles was also evaluated in terms of minimal inhibitory concentration. Moreover, the nanoparticles were submitted to in vitro studies for evaluating the drug permeability at the site of action. Results indicated that the obtained particles are potentially useful for the treatment of vaginal infections sustained by Candida albicans.