Rita Muzzalupo

Innovative bola-surfactant niosomes as topical delivery systems of 5-fluorouracil for the treatment of skin cancer.

An innovative niosomal system made up of alpha,omega-hexadecyl-bis-(1-aza-18-crown-6) (Bola), Span 80 and cholesterol (2:5:2 molar ratio) was proposed as a topical delivery system for 5-fluorouracil (5-FU), largely used in the treatment of different forms of skin cancers. Bola-niosomes showed a mean size of approximately 400 nm, which were reduced to approximately 200 nm by a sonication procedure with a polydispersion index value of 0.1. Bola-niosomes showed a loading capacity of approximately 40% with respect to the amount of 5-FU added during the preparation. 5-FU-loaded bola-niosomes were tested on SKMEL-28 (human melanoma) and HaCaT (non-melanoma skin cancer with a specific mutations in the p53 tumor suppressor gene) to assess the cytotoxic activity with respect to the free drug. 5-FU-loaded bola-niosomes showed an improvement of the cytotoxic effect with respect to the free drug. Confocal laser scanning microscopy studies were carried out to evaluate both the extent and the time-dependent bola-niosome-cell interaction. The percutaneous permeation of 5-FU-loaded niosomes was evaluated by using human stratum corneum and epidermis membranes. Bola-niosomes provided an increase of the drug penetration of 8- and 4-folds with respect to a drug aqueous solution and to a mixture of empty bola-niosomes with a drug aqueous solution.

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.

Niosomes vs microemulsions: new carriers for topical delivery of Capsaicin.

The development of advanced biomaterials and drug-delivery systems has had a significant impact on our ability to treat several diseases. A new study was performed on niosomal formulations obtained from a mixture of commercial surfactants (Tween 80 and Span 80) to be applied topically for the release of Capsaicin. Capsaicin is the pungent principle of red pepper and it has a variety of pharmacological actions on the cardiovascular, respiratory and nervous systems. Niosomal carriers were prepared using a particular ratio between surfactants, to obtain systems with a specific HLB (10,12,14) and characterized in terms of dimension, morphology and their drug entrapment efficiency. Niosomes were compared to microemulsions prepared from the same surfactants in the same ratio, to evaluate their possible use in transdermal drug delivery. As regards the in vitro percutaneous permeation of Capsaicin from both microemulsions and niosomal formulations, it was carried out using diffusion Franz cells. The results indicate that niosomes could better promote the transdermal delivery of Capsaicin, with respect to microemulsions, even if both carriers could be an effective vehicle for topical delivery of this drug.

Co-encapsulation of antioxidants into niosomal carriers: gastrointestinal release studies for nutraceutical applications.

Recently niosomes have been used as nutraceutical vehicles of functional components, useful in the prevention of many diseases caused by oxidative stress, with the aim to control their delivery into the body and to increase the nutritional quality of food dairy products with which these products can be enriched. We decided to develop novel niosomal formulations containing nutritional supplements such as gallic acid, ascorbic acid, curcumin and quercetin as single agents and in combination, to evaluate the effect of the active molecules co-encapsulation on the physico-chemical properties of the carriers, on their antioxidant properties and capability of releasing the encapsulated materials. Results suggest that the co-encapsulations of gallic acid/curcumin and ascorbic acid/quercetin mix influence their physico-chemical properties and their entrapment efficiencies respect to the formulations containing the single antioxidant; also the antioxidants releases appeared to improve and their combinations resulted in a promoted ability of reducing free radicals, due to a synergic antioxidant action.

Doxorubicin loaded magneto-niosomes for targeted drug delivery

In chemotherapy the magnetic drug targeting to a specific organ or tissue is proposed on the assumption that magnetic fields are harmless to biological systems. In this light we have vehiculated doxorubicin as model drug by novel magneto-niosomes in order to evaluate the physico-chemical properties of the obtained formulations and the in vitro release profile. Tween 60 and Pluronic L64 have been used as surfactants and the formulation cytotoxicity has been performed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolum bromide and trypan blue dye esclusion tests. Results show that niosome dimensions and doxorubicin entrapment efficiencies are influenced by bilayer composition. In addition, formulations are able to control the deliver and release of the drug active form in a retarded manner. No additional toxicity, due to the encapsulation of ferrofluid into niosomes core, has been detected.

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.

Transferrin-Conjugated Pluronic Niosomes as a New Drug Delivery System for Anticancer Therapy

An efficient tumor-targeted niosomal delivery system for the vehiculation of doxorubicin hydrochloride as an anticancer agent was designed. Niosomes were prepared from a mixture of an opportunely modified Pluronic L64 surfactant and cholesterol as a membrane additive and characterized in terms of size and related distribution function and drug entrapment efficiency. After the preparation, transferrin was conjugated to niosomes to produce transferrin (Tf) niosomes, and the cytotoxicity of the final formulation was studied. The specific uptake of Tf niosomes into cells was evaluated via incubation of MCF-7 and MDA-MB-231 cells with fluorescently rhodamine-loaded Tf niosomes for various times and concentration intervals and further investigated by fluorescence microscopy. Results showed that doxorubicin can be easily encapsulated into niosomes, which are regular and spherical in shape. Moreover, transferrin conjugate niosomes demonstrated far greater extents of cellular uptake by MCF-7 and MDA-MB-231 cells, suggesting that they were mainly taken up by transferrin receptor-mediated endocytosis. Doxorubicin-loaded niosome anticancer activity was also achieved against MCF-7 and MDA-MB-231 tumor cell lines, and a significant reduction in viability in a dose- and time-related manner was observed. Finally, our formulation could be potentially useful as a target doxorubicin delivery system in anticancer therapy.

Co-encapsulation of lipophilic antioxidants into niosomal carriers: Percutaneous permeation studies for cosmeceutical applications

Niosomal vesicular systems containing resveratrol, alpha-tocopherol and curcumin as single agents and in combination, were designed with the aim to develop novel cosmeceutical formulations. The effects of antioxidants co-encapsulation on the physico-chemical properties of the carriers, their antioxidant properties and in vitro percutaneous permeation profiles were evaluated. Results showed that the co-encapsulation of resveratrol/curcumin and alpha-tocopherol/curcumin affected the physico-chemical properties of niosomes and the entrapment efficiencies values, respect to the formulations containing the single antioxidant. The antioxidants in vitro percutaneous permeations appeared to be controlled and improved respect to the corresponding free solutions used as control. Moreover the antioxidants combinations resulted in a promoted ability to reduce free radicals, due to a synergic antioxidant action.

Alkyl glucopyranoside-based niosomes containing methotrexate for pharmaceutical applications: Evaluation of physico-chemical and biological properties

We designed novel niosomes based on alkyl glucopyranoside surfactants and containing methotrexate as anticancer drug, to be used in the pharmaceutical field. The effects of surfactants with chains of different length on niosome size and their distribution, drug entrapment efficiencies and in vitro drug release were determined. Systems made of alkyl glucopyranosides and cholesterol form vesicles whose average size scales with the alkyl chains length of such surfactants. Vesicles size ranges between 300 and 500 nm, with low polydispersity index. In addition, the hemolytic activity of alkyl glucopyranosides as surfactant solutions or vesicular formulations was studied and compared, to identify possible structure-activity relationships. High methotrexate entrapment efficiency was obtained, confirming significant interactions between the drug and the niosomal matrices. After 24h the amount of methotrexate released from niosomal formulations is effectively delayed, compared to the free drug in solution. Hemolytic tests show that sugar-based surfactants are more hemolytic the longer is their alkyl chain. When the surfactants are in vesicular form, the reverse behavior holds. It was also inferred that vesicle formation reduces the surfactant toxicity. These niosomal formulations can be used as methotrexate delivery systems in anticancer therapy.

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.