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The development of biomedical applications is a transdisciplinary field that in recent years has involved researchers from chemistry, pharmacy, medicine, biology, biophysics, and biomechanical engineering. The fabrication of biomedical devices requires the use of biocompatible materials that do not damage living tissues and have some biomechanical characteristics. The use of polymeric membranes, as materials meeting the above-mentioned requirements, has become increasingly popular in recent years, with outstanding results in tissue engineering, for regeneration and replenishment of tissues constituting internal organs, in wound healing dressings, and in the realization of systems for diagnosis and therapy, through the controlled release of active substances. The biomedical application of hydrogel membranes has had little uptake in the past due to the toxicity of cross-linking agents and to the existing limitations regarding gelation under physiological conditions, but now it is proving to be a very promising field This review presents the important technological innovations that the use of membrane hydrogels has promoted, enabling the resolution of recurrent clinical problems, such as post-transplant rejection crises, haemorrhagic crises due to the adhesion of proteins, bacteria, and platelets on biomedical devices in contact with blood, and poor compliance of patients undergoing long-term drug therapies.

Classical melanoma therapy has several side effects that are responsible for a decrease in the final therapeutic efficacy. It is possible that the drug is degraded before reaching the target site and is metabolized by the body itself, resulting in repeated doses being administered throughout the day and a decrease in patient compliance. Drug delivery systems avoid degradation of the active ingredient, improve release kinetics, prevent the drug from being metabolized before reaching the site of action, and improve the safety and efficacy profiles of adjuvant cancer therapy. The solid lipid nanoparticles (SLNs) based on hydroquinone esterified with stearic acid realized in this work represent a chemotherapeutic drug delivery system that is useful in the treatment of melanoma. The starting materials were characterized by FT-IR and 1 H-NMR, while the SLNs were characterized by dynamic light scattering. In efficacy studies, their ability to influence anchorage-dependent cell proliferation was tested on COLO-38 human melanoma cells. Furthermore, the expression levels of proteins belonging to apoptotic mechanisms were determined by analyzing the role of SLNs in modulating the expression of p53 and p21WAF1/Cip1. Safety tests were conducted to determine not only the pro-sensitizing potential but also the cytotoxicity of SLNs, and studies were conducted to assess the antioxidant and anti-inflammatory activity of these drug delivery.

Exposure to ultraviolet (UV) radiation causes harmful effects on the skin, such as inflammatory states and photoaging, which depend strictly on the form, amount, and intensity of UV radiation and the type of individual exposed. Fortunately, the skin is endowed with a number of endogenous antioxidants and enzymes crucial in its response to UV radiation damage. However, the aging process and environmental stress can deprive the epidermis of its endogenous antioxidants. Therefore, natural exogenous antioxidants may be able to reduce the severity of UV-induced skin damage and aging. Several plant foods constitute a natural source of various antioxidants. These include gallic acid and phloretin, used in this work. Specifically, polymeric microspheres, useful for the delivery of phloretin, were made from gallic acid, a molecule that has a singular chemical structure with two different functional groups, carboxylic and hydroxyl, capable of providing polymerizable derivatives after esterification. Phloretin is a dihydrochalcone that possesses many biological and pharmacological properties, such as potent antioxidant activity in free radical removal, inhibition of lipid peroxidation, and antiproliferative effects. The obtained particles were characterized by Fourier transform infrared spectroscopy. Antioxidant activity, swelling behavior, phloretin loading efficiency, and transdermal release were also evaluated. The results obtained indicate that the micrometer-sized particles effectively swell, and release the phloretin encapsulated in them within 24 h, and possess antioxidant efficacy comparable to that of free phloretin solution. Therefore, such microspheres could be a viable strategy for the transdermal release of phloretin and subsequent protection from UV-induced skin damage.

The growing demand for drug carriers and green-technology-based tissue engineering materials has enabled the fabrication of different types of micro- and nano-assemblies. Hydrogels are a type of material that have been extensively investigated in recent decades. Their physical and chemical properties, such as hydrophilicity, resemblance to living systems, swelling ability and modifiability, make them suitable to be exploited for many pharmaceutical and bioengineering applications. This review deals with a brief account of green-manufactured hydrogels, their characteristics, preparations, importance in the field of green biomedical technology and their future perspectives. Only hydrogels based on biopolymers, and primarily on polysaccharides, are considered. Particular attention is given to the processes of extracting such biopolymers from natural sources and the various emerging problems for their processing, such as solubility. Hydrogels are catalogued according to the main biopolymer on which they are based and, for each type, the chemical reactions and the processes that enable their assembly are identified. The economic and environmental sustainability of these processes are commented on. The possibility of large-scale processing in the production of the investigated hydrogels are framed in the context of an economy aimed at waste reduction and resource recycling., Competing Interests: The authors declare no conflicts of interest.

Coated stents are defined as innovative stents surrounded by a thin polymer membrane based on polytetrafluoroethylene (PTFE)useful in the treatment of numerous vascular pathologies. Endovascular methodology involves the use of such devices to restore blood flow in small-, medium- and large-calibre arteries, both centrally and peripherally. These membranes cross the stent struts and act as a physical barrier to block the growth of intimal tissue in the lumen, preventing so-called intimal hyperplasia and late stent thrombosis. PTFE for vascular applications is known as expanded polytetrafluoroethylene (e-PTFE) and it can be rolled up to form a thin multilayer membrane expandable by 4 to 5 times its original diameter. This membrane plays an important role in initiating the restenotic process because wrapped graft stent could be used as the treatment option for trauma devices during emergency situations and to treat a number of pathological vascular disease. In this review, we will investigate the multidisciplinary techniques used for the production of e-PTFE membranes, the advantages and disadvantages of their use, the innovations and the results in biomedical and surgery field when used to cover graft stents.

This article describes the preparation, characterization, and performance evaluation of functional microspheres useful for the release of ciprofloxacin. The particles were obtained using D-mannose, a natural aldohexose sugar, and resveratrol, a powerful antioxidant. In particular, the above compounds were initially converted into D-mannose carboxylate and resveratrol methacrylate and, therefore, subjected to an esterification reaction. The resulting product was used for the preparation of the microspheres which were characterized by light scattering, FT-IR spectrophotometry and scanning electron microscopy (SEM). Subsequently, their degree of bloating was evaluated at pH 1.2 to simulate the pH of the stomach, at pH 6.8 and pH 7.4 to mimic the intestinal environment. The antibiotic ciprofloxacin was then loaded into the microspheres, with an encapsulation efficiency of 100%. The cumulative amount of drug released was 55% at pH 6.8 and 99% at pH 7.4. The tests conducted to evaluate the antibacterial activity demonstrated the ability of the microspheres obtained to inhibit the growth of Escherichia coli . The antioxidant efficacy, due to the presence of resveratrol in their structure, was confirmed using rat liver microsomal membranes. The results obtained have highlighted how the microspheres based on D-mannose and resveratrol can be considered promising multifunctional vectors useful in the treatment of intestinal and urinary infections.

Different strategies have been investigated for a more satisfactory treatment of advanced breast cancer, including the adjuvant use of omega-3 polyunsaturated fatty acids (PUFAs). These nutritional compounds have been shown to possess potent anti-inflammatory and antiangiogenic activities, the capacity to affect transduction pathways/receptors involved in cell growth and to reprogram tumor microenvironment. Omega-3 PUFA-containing nanoformulations designed for drug delivery in breast cancer were shown to potentiate the effects of enclosed drugs, enhance drug delivery to target sites, and minimize drug-induced side effects. We have critically analyzed here the results of the most recent studies investigating the effects of omega-3 PUFA-containing nanoformulations in breast cancer. The anti-neoplastic efficacy of omega-3 PUFAs has also been convincingly demonstrated by using preclinical in vivo models of ovarian cancer. The results obtained are critically analyzed here and seem to provide a sufficient rationale to move to still lacking interventional clinical trials, as well as to evaluate possible advantages of enclosing omega-3 PUFAs to drug-delivery nanosystems for ovarian cancer. Future perspectives in this area are also provided.

Linolenic acid (LNA) is the most highly consumed polyunsaturated fatty acid found in the human diet. It possesses anti-inflammatory effects and the ability to reverse skin-related disorders related to its deficiency. The purpose of this work was to encapsulate LNA in solid lipid nanoparticles (SLNs) based on curcumin, resveratrol and capsaicin for the treatment of atopic dermatitis. These compounds were first esterified with oleic acid to obtain two moonoleate and one oleate ester, then they were used for SLN matrix realization through the emulsification method. The intermediates of the esterification reaction were characterized by FT-IR and 1 N-MR analysis. SLNs were characterized by dimensional analysis and encapsulation efficiency. Skin permeation studies, antioxidant and anti-inflammatory activities were evaluated. LNA was released over 24 h from nanoparticles, and resveratrol monooleate-filled SLNs exhibited a good antioxidant activity. The curcumin-based SLNs loaded or not with LNA did not induce significant cytotoxicity in NCTC 2544 and THP-1 cells. Moreover, these SLNs loaded with LNA inhibited the production of IL-6 in NCTC 2544 cells. Overall, our data demonstrate that the synthesized SLNs could represent an efficacious way to deliver LNA to skin cells and to preserve the anti-inflammatory properties of LNA for the topical adjuvant treatment of atopic dermatitis.

α-tocopherol (α-T) has the highest biological activity with respect to the other components of vitamin E; however, conventional formulations of tocopherol often fail to provide satisfactory bioavailability due to its hydrophobic characteristics. In this work, α-tocopherol-loaded nanoparticles based on chitosan were produced by membrane emulsification (ME). A new derivative was obtained by the cross-linking reaction between α-T and chitosan (CH) to preserve its biological activity. ME was selected as a method for nanoparticle production because it is recognized as an innovative and sustainable technology for its uniform-particle production with tuned sizes and high encapsulation efficiency (EE%), and its ability to preserve the functional properties of bioactive ingredients operating in mild conditions. The reaction intermediates and the final product were characterized by 1 HNMR, Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), while the morphological and dimensional properties of the nanoparticles were analyzed using electronic scanning microscopy (SEM) and dynamic light scattering (DLS). The results demonstrated that ME has high potential for the development of α-tocopherol-loaded nanoparticles with a high degree of uniformity (PDI lower than 0.2), an EE of almost 100% and good mechanical strength, resulting in good candidates for the production of functional nanostructured materials for drug delivery. In addition, the chemical bonding between chitosan and α-tocopherol allowed the preservation of the antioxidant properties of the bioactive molecule, as demonstrated by an enhanced antioxidant property and evaluated through in vitro tests, with respect to the starting materials.

Xanthan gum-based microspheres and hydrogels, useful for targeted colorectal release of omega-3 polyunsaturated fatty acids (PUFAs), were successfully prepared and characterized. In particular, the microsphere size, as well as the high hydrogel swelling degree at pH 7.4, and the omega-3 PUFA loading efficiency of both the materials suggested their suitability for colorectal delivery. Moreover, the antioxidant efficiency of the xanthan gum based materials suggests their ability to protect the omega-PUFA cargo. We demonstrated that α-linolenic acid (ALA 18:3ω-3) carried by the materials increased significantly its ability to reduce colorectal cancer cell growth in vitro. On the contrary, docosahexaenoic acid (DHA, 22:6ω-3) enclosed in the hydrogel formulation did not enhance its already high anti-neoplastic potential. The improved anti-neoplastic efficacy of ALA enclosed in both the xanthan gum-based formulations further supports the hypothesis of a potential use of this omega-3 PUFA as a suitable and more sustainable alternative to the fish-derived DHA., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Aim: The aim of the present study was to prepare a hydrogel, based on ellagic acid and glycine, embedded with folic acid, as a subcutaneous implant for the treatment of breast cancer. The function of folic acid is to selectively and actively target tumor cells which are well-known to overexpress folic acid receptors on their surface., Materials and Methods: A pro-drug based on L-glycine and ellagic acid, was functionalized with a polymerizable group and loaded with folic acid to make it more natural, non-toxic, compatible and specific for the site of action. Cytotoxicity against MCF-7 cells was also evaluated. Release studies of folic acid were conducted on aliquots of hydrogel at different pH (6.2 and 7.4) and time-points (1, 6, 12 and 24 h) using a shaking water bath at 37°C (body temperature)., Results: Our results show that folic acid release by the hydrogel is characterized by a slow kinetic release, especially at pH 6.2. Moreover, it was evidenced that the exposure of human breast cancer cells to ellagic acid-based hydrogel containing folic acid significantly reduced cell viability.

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., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Tween surfactants possess very interesting properties such as biodegradability, biocompatibility, and low toxicity. The synthesis of acrylate monomers by means of the chemical modification of polysorbate surfactants Tween 20, 40, and 60 with unsaturated groups is described. Monomers were obtained as a result of the reaction of methacrylic anhydride with different grades of Tween surfactants. Further polymerization was carried out in tetrahydrofuran, dimethylformamide, and a mixture of water-tetrahydrofuran. Physicochemistry properties of the polymer networks were investigated, and the obtained results reveal that they strongly depend on the type of solvent used during the polymerization, as well as on the concentration of the casting solution. In particular, our study demonstrated that, depending on the solvent boiling point, i.e., the facility to remove the solvent from the polymer matrix, it is possible to predict properties of the network morphology. Moreover, in vitro studies on controlled release were accomplished to demonstrate the possibility of utilizing these new materials as drug delivery systems. All resulting networks represent a novel class of cross-linked polymeric materials useful both in pharmaceutical and chemical applications.

In this study we report the synthesis and characterisation of cellulose ferulate, lipoate and alpha-tocopherulate, and their ability to inhibit lipid peroxidation in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals: tert-butyl hydroperoxide and 2,2'-azobis-(2-amidinopropane). We also compared the antioxidant efficiency of the ferulate derivatives obtained through two different synthetic runs, and of a tocopherulate derivative prepared from 6-carboxycellulose. This study showed that the designed systems, preserving the antioxidant activity of the free substrates, are more effective in protecting from tert-butyl hydroperoxide than from 2,2'-azobis-(2-amidinopropane). Moreover, the cellulose ferulate with the higher degree of substitution acted as the best antioxidant.

Carotenoids exhibit preventive effects against major diseases, including cancer and atherosclerosis. However, experimental studies on carotenoid functions in cultured cells are limited by the absence of an adequate method of solubilizing carotenoids, since they are unstable when exposed to light or oxygen and highly hydrophobic. In this study, we developed a niosomal formulation, consisting of non-ionic surfactants and cholesterol, which both solubilized and stabilized beta-carotene and that allowed to deliver it to cultured cells at concentrations spanning the range of physiological levels. beta-Carotene contained in niosomes was highly resistant to sunlight, high temperatures and oxidative stress induced by different sources of free radicals. The carotenoid was extremely stable in culture medium up to 96 h. Moreover, it was easily taken up by both immortalized and transformed cells at carotenoid concentrations which ranged from 0.1 to 2 microM. Therefore, niosomes provide a convenient, nontoxic and inexpensive vehicle for beta-carotene in cell culture.

Although an antioxidant mechanism has been involved in the beneficial effects of ferulic acid in human diseases, there are few reports on the antioxidant properties of this compound in isolated membranes and intact cells. Here, we evaluated the ability of ferulic acid in inhibiting lipid peroxidation in rat liver microsomal membranes and reactive oxygen species production in NIH-3T3 fibroblasts, induced by both tert-BOOH and AAPH. We also compared its antioxidant efficiency with that of other antioxidants, such as alpha-tocopherol, beta-carotene, and ascorbic acid, added alone or in combination. Ferulic acid acted as a potent antioxidant in our models, being more effective in protecting from tert-BOOH than from AAPH. Moreover, the compound was the most effective among the antioxidants tested. Synergistic interactions were observed when the compound was used in combination with the other antioxidants, suggesting that they can cooperate in preserving physiological integrity of cells exposed to free radicals.