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Inclusion of lipids or polymers with a transition temperature closer to physiological body temperature (40–42 °C) is a strategy used in tumor therapy for more than 30 years, because it allows induction of drug release from delivery systems by mild hyperthermia. Unfortunately, most of these thermo-sensitive carriers are removed from circulation before completion of their function. Thus, novel multi-functional niosomes possessing spontaneous stealth and thermo-sensitive properties were developed from L64 Pluronic ® and L64ox as its derivative, in presence or absence of cholesterol. The use of L64 both as amphiphilic constituent and thermo-sensitive molecule, gave the possibility to bypass the use of additional excipients and increased the system biocompatibility. Niosomes diameter ranged from 400 to 750 nm and were long term stable. Calcein and 5-FU possess great affinity to niosomal matrices rich in PEO groups. Negative Z-potential values were attributed to the negative charges onto the niosomes surface and generally change according to the temperature. The in vitro drugs release studies were performed at 25 °C, 37 °C and 42 °C, that are representative of certain conditions (storage, physiological condition and mild hyperthermia, respectively). Results showed that L64-based niosomes possess spontaneous thermo-sensitive properties: drugs releases were found to be more pronounced at 42 °C. These early results are a promising first step for the development of multi-functional devices that combine several advantages such as stealth properties and temperature controllability at the desired location and time, for a more specific and efficient pharmacological therapy. [ABSTRACT FROM AUTHOR]

Photostability studies were performed on topical formulations containing diclofenac (DC). Niosomal gels were designed as photostabilization systems and ascorbic acid was also added to the new topical formulations because of its antioxidant property. Photodegradation tests were applied on commercial formulations containing DC and novel prepared gels, according to the ICH rules. The experiments were monitored by spectrophotometry and the data processed by multivariate curve resolution analysis to estimate the spectra and concentration profiles of evolved components. Characterization of niosomes was evaluated by size and distribution measurement, morphological analysis and encapsulation efficiency. Permeation experiments were performed across rabbit ear skin up to 24 h. Photodegradation rate of DC was found very fast in commercial formulation, with a residual content of 90% after only 4.38 min under a radiant exposure of 450 W/m 2 . Photostability resulted increased significantly when the drug was entrapped in niosomal systems. The best results were obtained by reaching a 10% degradation after 50.00 min of light exposure after incorporation of DC in niosomes in presence of 5% ascorbic acid. Moreover, niosomal gel also influenced the permeation capability of DC by enhancing the transdermal delivery of the drug. The cumulative dose permeated of DC from niosomal gel was about three times that obtained with the commercial gel. [ABSTRACT FROM AUTHOR]

Abstract: 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 500nm, 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. [Copyright &y& Elsevier]

Abstract: Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX–CS–NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from Nα,Nε-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX–CS–NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX–CS–NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy. [Copyright &y& Elsevier]

Abstract: The central motivation for this study was to evaluate if the increased hydrophilic drug permeation across the skin, which is always observed in presence of vesicular systems, is dependent on the structural organization of niosomes, that are used to transport the active molecules, or if it is only dependent on the surfactant dual nature. To answer this question, non-ionic surfactants belonging to the class of Pluronic and sucrose esters were used both as components of niosomal systems or in the form of sub-micellar solutions. The obtained niosomes were characterized by their entrapment efficiency, size and morphology. The enhancing effect of niosomes on the ex vivo percutaneous penetration of a model drug was investigated using a Franz-type diffusion chamber and compared to that obtained by using sub-micellar solution of surfactant or achieving pretreatment of the skin with surfactants’ sub-micellar solution or empty niosomes. The results suggest that the surfactants used in this study could be considered as percutaneous permeation enhancers only when they are in the form of drug-loaded vesicular systems: no percutaneous promotion was achieved by using sub-micellar solution containing free Sulfadiazine sodium salt or performing pretreatment with empty niosomes or sub-micellar solutions of the surfactant. In our experiments, only niosomes act as effective transdermal drug delivery systems. [Copyright &y& Elsevier]

Abstract: Colon-targeted delivery devices based on methacrylic functionalized Tween monomer networks, useful for 5-FU or Ferulic acid site-specific release, were synthesized. The basic design consists of methacrylic functionalized Tween monomer-based networks prepared with or without acrylic acid as co-monomer. The swelling behaviour and loaded drugs release from these gels was studied as a function of pH. The devices showed a strong pH-dependent swelling behaviour, allowing a maximum release at pH 7.4. The acrylic acid introduction increased the polymeric gels pores size, as evidenced by the loading efficiency increase, but also reduced the amount of released drug in basic media compared to analogous network not containing the co-monomer. This behaviour, already found in the matrix swelling, could be attributed to a slower hydrolysis kinetics of the ester bond in functionalized Tween monomers, which implies a reduced ability to absorb water from a basic medium, resulting in a lower capacity to release the loaded drug. Since our device possesses a maximum drug release in the media at pH 7.4, it could be used for colon-targeted drug delivery of both 5-FU and Ferulic acid. [Copyright &y& Elsevier]

Abstract: Topical commercial formulations containing diclofenac (DC) were submitted to photostability tests, according to the international rules, showing a clear degradation of the drug. The degradation process was monitored by applying the multivariate curve resolution technique to the UV spectral data from samples exposed to stressing irradiation. This method was able to estimate the number of components evolved as well as to draw their spectra and concentration profiles. Three photoproducts (PhPs) were resolved by the analysis of photodegradation kinetics, according to two consecutive reactions with a mechanism postulated as DC>PhP1 >PhP2 and PhP3. Photodegradation rate of DC in gel was found to be very fast, with a residual content of 90% only after 3.90min under a radiant exposure of 450Wm−2. Because of a very slow skin uptake of DC, a prolonged time of exposure to light could lead to a significant decrease of drug available or the uptake of undesired photoproducts. New gel formulations were designed to increase the photostability of DC by incorporating chemical light-absorbers or entrapping the drug into cyclodextrin. Drug photostability resulted increased significantly in comparison with that of the commercial formulations. The gel containing the light-absorbers such as octisilate, octyl methoxycinnamate and a combination thereof showed a residual DC of 90% up to 12.22min, 13.75min and 15.71min, respectively, under the same irradiation power. The best results were obtained by incorporating the drug in β-cyclodextrin with a degradation of 10% after 25.01min of light exposure. [Copyright &y& Elsevier]

The natural capability shown by cationic vesicles in interacting with negatively charged surfaces or biomolecules has recently attracted increased interest. Important pharmacological advantages include the selective targeting of the tumour vasculature, the promotion of permeation across cell membranes, as well as the influence of cationic vesicles on drug delivery. Accordingly, cationic amphiphiles derived from amino acids may represent an alternative to traditional synthetic cationic surfactants due to their lower cytotoxicity. The importance of a synthesized lysine-based gemini surfactant (labelled C 6 (LL) 2 ) was evaluated in drug delivery by designing cationic niosomes as usable pharmaceutical tools of chemotherapeutics and antibiotics, respectively like methotrexate and tetracycline. The influence of formulation factors on the vesicles’ physical-chemical properties, drug entrapment efficiency, in vitro release and ex-vivo skin permeation were investigated. A niosomal gel containing the gemini surfactant was also tested as a viable multi-component topical formulation. Results indicate that in the presence of cholesterol, C 6 (LL) 2 was able to form stable and nanosized niosomes, loading hydrophilic or hydrophobic molecules. Furthermore, in vitro release studies and ex-vivo permeation profiles showed that C 6 (LL) 2 -based vesicles behave as sustained and controlled delivery systems in the case of parenteral administration, and as drug percutaneous permeation enhancers after topical application. Finally, cationic C 6 (LL) 2 acts as a carrier constituent, conferring peculiar and interesting functionality to the final formulation. [ABSTRACT FROM AUTHOR]

Abstract: In the present work, we report the synthesis of cellulose hydrogel containing ferulic moieties and the evaluation of its antioxidant and scavenger activity. Acrylic groups were inserted onto cellulose backbone by a heterogeneous synthesis to produce two cellulose monomers with different degree of substitution (DS). The radical copolymerization of acrylcellulose (AcrC) with N,N-dimethylacrylamide (DMAA) was carried out in NH3/Urea aqueous solution, in a range of composition between 24 and 60wt% of AcrC. The obtained hydrogels were characterized by infrared spectroscopy (FT-IR). Their equilibrium swelling degree (α%) was evaluated. They showed good swelling behavior in simulating gastric, intracellular and intestinal fluids and no more different at various pH. The ferulic moieties were directly grafted on the free hydroxylic groups of cellulose hydrogel by acylation, using dicyclohexylcarbodiimide (DCC) and 4-hydroxybenzotriazole (HBT) as condensation agents. Finally, the antioxidant activity in inhibiting the lipid peroxidation, in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals, 2,2′-azobis (2-amidinopropane) (AAPH) and tert-butyl hydroperoxide (tert-BOOH), was evaluated. The effects of scavenging DPPH (1,1-diphenyl-2-picrylhydrazyl) radicals were also investigated. Hydrogel was found to be very efficient scavengers of DPPH radicals. The results strongly suggested that the antioxidant hydrogel neutralize free radicals. This biomaterial could be successfully applied in pharmaceutical field both as prodrug of trans-ferulic acid than as carrier for photo and thermo-degradable drugs to improve their stability. [Copyright &y& Elsevier]

Abstract: We prepared cellulose cotton fibers containing ampicillin moieties and evaluated their antibacterial activity. In spite of recent progress in experimental and clinical medicine, the problem of chronic wounds treatment remains to be solved. In fact conventional methods are based on solutions of antibiotics and antiseptics and ointment bandages but the efficacy of this method is low and so the idea to use modified cotton gauzes would have to prevent infections insorgence during wounds healing. Ampicillin, a large spectrum antibiotic, was covalently coupled to cellulose backbone of hydrophilic cotton fibers by a heterogeneous synthesis to produce a functionalized biopolymer with a satisfactory degree of substitution (DS) and antibacterial activity. The obtained biopolymer was characterized by infrared spectroscopy (FT-IR). Finally, the antibacterial activity in inhibiting microorganism growth in Petri dishes, was evaluated. The results suggested that these biomaterials posses an excellent “in vitro” antibacterial activity and so they can be efficiently employed in biomedical fields for chronic wounds management to ensure a valid protection against infections and contaminations. Biopolymers so functionalized were found to be very efficient to contrast sensible bacteria growth. [Copyright &y& Elsevier]