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1.
Colloids Surf B Biointerfaces ; 138: 117-27, 2016 Feb 01.
Article in English | MEDLINE | ID: mdl-26674840

ABSTRACT

The growing demand for efficient chemotherapy in many cancers requires novel approaches in target-delivery technologies. Nanomaterials with pH-responsive behavior appear to have potential ability to selectively release the encapsulated molecules by sensing the acidic tumor microenvironment or the low pH found in endosomes. Likewise, polyethylene glycol (PEG)- and poloxamer-modified nanocarriers have been gaining attention regarding their potential to improve the effectiveness of cancer therapy. In this context, DOX-loaded pH-responsive nanoparticles (NPs) modified with PEG or poloxamer were prepared and the effects of these modifiers were evaluated on the overall characteristics of these nanostructures. Chitosan and tripolyphosphate were selected to form NPs by the interaction of oppositely charged compounds. A pH-sensitive lysine-based amphiphile (77KS) was used as a bioactive adjuvant. The strong dependence of 77KS ionization with pH makes this compound an interesting candidate to be used for the design of pH-sensitive devices. The physicochemical characterization of all NPs has been performed, and it was shown that the presence of 77KS clearly promotes a pH-triggered DOX release. Accelerated and continuous release patterns of DOX from CS-NPs under acidic conditions were observed regardless of the presence of PEG or poloxamer. Moreover, photodegradation studies have indicated that the lyophilization of NPs improved DOX stability under UVA radiation. Finally, cytotoxicity experiments have shown the ability of DOX-loaded CS-NPs to kill HeLa tumor cells. Hence, the overall results suggest that these pH-responsive CS-NPs are highly potent delivery systems to target tumor and intracellular environments, rendering them promising DOX carrier systems for cancer therapy.


Subject(s)
Chitosan/chemistry , Doxorubicin/chemistry , Nanoparticles/chemistry , Surface-Active Agents/chemistry , Antibiotics, Antineoplastic/chemistry , Antibiotics, Antineoplastic/pharmacokinetics , Antibiotics, Antineoplastic/pharmacology , Cell Survival/drug effects , Doxorubicin/pharmacokinetics , Doxorubicin/pharmacology , Drug Carriers/chemistry , Drug Liberation , HeLa Cells , Humans , Hydrogen-Ion Concentration , Lysine/chemistry , Poloxamer/chemistry , Polyethylene Glycols/chemistry , Polyphosphates/chemistry , Spectrophotometry , Spectroscopy, Fourier Transform Infrared
2.
Mater Sci Eng C Mater Biol Appl ; 57: 100-6, 2015 Dec 01.
Article in English | MEDLINE | ID: mdl-26354244

ABSTRACT

The pH-responsive delivery systems have brought new advances in the field of functional nanodevices and might allow more accurate and controllable delivery of specific cargoes, which is expected to result in promising applications in different clinical therapies. Here we describe a family of chitosan-TPP (tripolyphosphate) nanoparticles (NPs) for intracellular drug delivery, which were designed using two pH-sensitive amino acid-based surfactants from the family N(α),N(ε)-dioctanoyl lysine as bioactive compounds. Low and medium molecular weight chitosan (LMW-CS and MMW-CS, respectively) were used for NP preparation, and it was observed that the size distribution for NPs with LMW-CS were smaller (~168 nm) than that for NPs prepared with MMW-CS (~310 nm). Hemolysis assay demonstrated the pH-dependent biomembrane disruptional capability of the constructed NPs. The nanostructures incorporating the surfactants cause negligible membrane permeabilization at pH7.4. However, at acidic pH, prevailing in endosomes, membrane-destabilizing activity in an erythrocyte lysis assay became evident. When pH decreased to 6.6 and 5.4, hemolytic capability of chitosan NPs increased along with the raise of concentration. Furthermore, studies with cell culture showed that these pH-responsive NPs displayed low cytotoxic effects against 3T3 fibroblasts. The influence of chitosan molecular weight, chitosan to TPP weight ratio, nanoparticle size and nature of the surfactant counterion on the membrane-disruptive properties of nanoparticles was discussed in detail. Altogether, the results achieved here showed that by inserting the lysine-based amphiphiles into chitosan NPs, pH-sensitive membranolytic and potentially endosomolytic nanocarriers were developed, which, therefore, demonstrated ideal feasibility for intracellular drug delivery.


Subject(s)
Anti-Bacterial Agents/chemistry , Chitosan/chemistry , Delayed-Action Preparations/chemistry , Nanocapsules/chemistry , Polyphosphates/chemistry , Surface-Active Agents/chemistry , Absorption, Physicochemical , Animals , Anti-Bacterial Agents/administration & dosage , Delayed-Action Preparations/administration & dosage , Diffusion , Drug Synergism , Hydrogen-Ion Concentration , Mice , Nanocapsules/ultrastructure
3.
Nanomaterials (Basel) ; 4(2): 454-484, 2014 Jun 12.
Article in English | MEDLINE | ID: mdl-28344232

ABSTRACT

Engineered nanomaterials are emerging functional materials with technologically interesting properties and a wide range of promising applications, such as drug delivery devices, medical imaging and diagnostics, and various other industrial products. However, concerns have been expressed about the risks of such materials and whether they can cause adverse effects. Studies of the potential hazards of nanomaterials have been widely performed using cell models and a range of in vitro approaches. In the present review, we provide a comprehensive and critical literature overview on current in vitro toxicity test methods that have been applied to determine the mechanisms underlying the cytotoxic effects induced by the nanostructures. The small size, surface charge, hydrophobicity and high adsorption capacity of nanomaterial allow for specific interactions within cell membrane and subcellular organelles, which in turn could lead to cytotoxicity through a range of different mechanisms. Finally, aggregating the given information on the relationships of nanomaterial cytotoxic responses with an understanding of its structure and physicochemical properties may promote the design of biologically safe nanostructures.

4.
J Photochem Photobiol B ; 125: 83-9, 2013 Aug 05.
Article in English | MEDLINE | ID: mdl-23751539

ABSTRACT

Cytisus scoparius L. is used in folk medicine for the treatment of several ailments in which the antioxidant and anti-inflammatory effects of its carotenoid and flavonoid content is suggested to play an important role. We postulate that flavonoid- and carotenoid-rich extracts from C. scoparius may become useful in the preparation of formulations for topical application to protect the skin against oxidative damage mediated by high energy UV light radiation. The aim of this work was to apply an extraction process to obtain a bioactive extract from C. scoparius for the potential use in topical applications. Aqueous and ethanolic extracts from C. scoparius were characterized for its reducing capacity, radical scavenging capacity, and on the reactive oxygen and nitrogen species (ROS, RNS). The extracts showed activities comparable to that of synthetic antioxidants, and absence of skin-irritant effects at 1%. Those make them good candidates to be used in topical applications as active ingredients.


Subject(s)
Antioxidants/pharmacology , Cytisus , Plant Extracts/pharmacology , Administration, Topical , Aldehydes/isolation & purification , Animals , Chemical Fractionation , Erythrocytes/drug effects , Erythrocytes/pathology , Flavonoids/isolation & purification , Freeze Drying , Hemolysis , Humans , In Vitro Techniques , Ketones/isolation & purification , Lipid Peroxidation/drug effects , Oxidative Stress/drug effects , Phenols/isolation & purification , Plant Extracts/chemistry , Plant Stems , Rats , Skin/drug effects
5.
Photochem Photobiol Sci ; 12(5): 805-12, 2013 May.
Article in English | MEDLINE | ID: mdl-23361471

ABSTRACT

PURPOSE: The aim of this study was to evaluate the cytotoxic, phototoxic, genotoxic and photogenotoxic potential of gemifloxacin mesylate (GFM), its main synthetic impurity (SI) and one isolated and structurally elucidated degradation product (DP). METHODS: The neutral red uptake (NRU) and reduction of 2,5-diphenyl-3,-(4,5-dimethyl-2-thiazolyl)tetrazolium bromide (MTT) assays were performed as in vitro endpoints to evaluate cytotoxicity and phototoxicity in a 3T3 cell line, and predict toxicity and/or phototoxicity after systemic administration of the drug. The in vitro alkaline single-cell electrophoresis (comet) assay was used to evaluate the genotoxic and photogenotoxic potential of the substances using the same cell line. RESULTS: The results showed that the SI and the DP are more cytotoxic and phototoxic than the drug GFM using the 3T3 cell line. In the comet assay, the drug GFM was found to be more genotoxic and photogenotoxic than its related substances. CONCLUSIONS: Our findings highlight the relevance of the biological safety studies to increase the knowledge regarding the toxic potential of the related substances, which can be associated with the drug side effects and toxicity.


Subject(s)
Fluoroquinolones/chemistry , Naphthyridines/chemistry , 3T3 Cells , Animals , Cell Survival/drug effects , Comet Assay , DNA/drug effects , DNA/metabolism , DNA/radiation effects , Fluoroquinolones/toxicity , Formazans/chemistry , Gemifloxacin , Mice , Naphthyridines/toxicity , Neutral Red/chemistry , Oxidation-Reduction , Tetrazolium Salts/chemistry , Ultraviolet Rays
6.
J AOAC Int ; 89(5): 1367-72, 2006.
Article in English | MEDLINE | ID: mdl-17042189

ABSTRACT

Cefepime is a new parenteral cephalosporin that has been described as a fourth-generation, broad-spectrum antibiotic. This paper reports the development and in-house validation of an agar diffusion bioassay using a cylinder-plate method for the determination of cefepime in powder for injection. The validation performed yielded good results in terms of linearity, precision, accuracy, and robustness. The assay is based on the inhibitory effect of cefepime upon the strain of Micrococcus luteus ATCC 10240 used as the test microorganism. The results of assays were treated statistically by analysis of variance (ANOVA) and were found to be linear (r = 0.99993) in the selected range of 8.0-32.0 microg/mL; precise [repeatability: relative standard deviation (RSD) = 1.39%, intermediate precision: between-day RSD = 1.77%, and between-analyst RSD = 1.97%] and accurate. Comparison of bioassay and liquid chromatography by ANOVA showed no significant difference between methodologies. The results demonstrated the validity of the proposed bioassay, which is a simple and useful alternative methodology for cefepime determination in routine quality control.


Subject(s)
Biological Assay/methods , Cephalosporins/analysis , Analysis of Variance , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/analysis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/standards , Biological Assay/standards , Biological Assay/statistics & numerical data , Cefepime , Cephalosporins/administration & dosage , Cephalosporins/pharmacology , Cephalosporins/standards , Chromatography, Liquid , Injections , Mass Spectrometry , Micrococcus luteus/drug effects , Powders , Reference Standards , Reproducibility of Results
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