This review is focused essentially on the synthesis and applications of gold nanoparticles in the field of medicine and targeted drug delivery. Nanotechnology has become one of the most interesting and advanced areas of research in this field. Among nanoparticles, gold nanoparticles demonstrate special advantages in this field due to their unique properties, small size and high surface area-to-volume ratio.These particles have been widely used in various biomedical applications and drug delivery systems due to their inert nature, stability, high dispersity, non-cytotoxicity and biocompatibility.
Several pathologies such as neurodegeneration and cancer are associated with aging, which is affected by many genetic and environmental factors. Healthy aging conceives human longevity, possibly due to carrying the defensive genes. For instance, FOXO (forkhead box O) genes determine human longevity. FOXO transcription factors are involved in the regulation of longevity phenomenon via insulin and insulin-like growth factor signaling. Only one FOXO gene (FOXO DAF-16) exists in invertebrates, while four FOXO genes, that is, FOXO1, FOXO3, FOXO4, and FOXO6 are found in mammals. These four transcription factors are involved in the multiple cellular pathways, which regulate growth, stress resistance, metabolism, cellular differentiation, and apoptosis in mammals. However, the accurate mode of longevity by FOXO factors is unclear until now. This article describes briefly the existing knowledge that is related to the role of FOXO factors in human longevity.
Context: During diabetes mellitus, non-enzymatic reaction between amino groups of protein and carbonyl of reducing sugars (Millard reaction) is responsible for the major diabetic complications. Various efforts have been made to influence the process of protein glycation. Objectives: This review article provides an extensive survey of various studies published in scientific literature to understand the process of protein glycation and its measurement. Moreover, evaluation and identification of potential inhibitors (antiglycation agents) of protein glycation from natural and synthetic sources and their mechanism of action in vitro and in vivo are also addressed. Method: In this review article, the mechanism involved in the formation of advanced glycation end products (AGEs) is discussed, while in second and third parts, promising antiglycation agents of natural and synthetic sources have been reviewed, respectively. Finally, in vivo studies have been addressed. This review is mainly compiled from important databases such as Science, Direct, Chemical Abstracts, SciFinder, and PubMed. Results: During the last two decades, various attempts have been made to inhibit the process of protein glycation. New potent inhibitors of protein glycation belonging to different classes such as flavonoids, alkaloids, terpenes, benzenediol Schiff bases, substituted indol, and thio compounds have been identified. Conclusion: Antiglycation therapy will be an effective strategy in future to prevent the formation of AGEs for the management of late diabetic complications Current review article highlighted various compounds of natural and synthetic origins identified previously to inhibit the protein glycation and formation of AGEs in vitro and in vivo.
The aim of present study was to enhance topical permeation of clotrimazole gel preparation by using various permeability enhancers such as coconut oil, pistachio oil and sodium lauryl sulphate (SLS). Clotrimazole gel preparations were prepared and optimized by using three factor, five level central composite design. A second-order polynomial equation was generated in order to estimate the effect of independent variables i.e. coconut oil (X 1 ), pistachio oil (X 2 ) and sodium lauryl sulphate (X 3 ) at various dependent variables i.e. flux (Y 1 ), lag time (Y 2 ), diffusion coefficient (Y 3 ), permeability coefficient (Y 4 ), and input rate (Y 5 ) of clotrimazole gel formulations. Ex vivo skin permeation study was performed through rat skin by using modified Franz diffusion cell system. Optimized formulation F8 exhibited highest flux 2.17 µg/cm 2 /min, permeability coefficient 0.0019 cm/min and input rate 1.543 µg/cm 2 /min, along with moderate lag time 77.27 min and diffusion coefficient 0.063 cm 2 /min, which is further supported by anti-fungal activity that exhibited more prominent zone of inhibition against Candida albicans, Aspergillus niger and Mucor. Thus, it can be concluded that permeation of clotrimazole gel was enhanced by various combination of coconut oil, pistachio oil and sodium lauryl sulphate but optimized formulation F8 containing 0.4 ml pistachio oil, 0.8 ml coconut oil and 0.04 g of SLS exhibited more pronounced and promising effect through rat skin.
Over the past few years, considerable attention has been focused on carrageenan based bionanocomposites due to their multifaceted properties like biodegradability, biocompatibility, and nontoxicity. Moreover, these composites can be tailored according to the desired purpose by using different nanofillers. The role of ferromagnetic nanoparticles in drug delivery is also discussed here in detail. Moreover, this article also presents a short review of recent research on the different types of the carrageenan based bionanocomposites and applications.
The absence of these base propenals upon gamma-radiolysis implies that although the initiating step of OH-radical and bleomycin action [i.e. H-abstraction at C(4')] may be the same, the bleomycin-iron complex must participate in subsequent steps en route to the base propenals. It is proposed that the bleomycin pathway may involve the interaction of the C(4')-peroxyl radical with the 'spent' bleomycin-iron complex by ligand exchange, under formation of a bleomycin-iron-peroxyl-radical complex, Blm(Fe4+,*OOR), which then decomposes by heterolysis into the alkoxy cation precursor +OR of the base propenal and reconstitution of the bleomycin-iron complex Blm(Fe,O)3+, i.e. gives rise to base propenal formation without the involvement of a C(4')-hydroperoxide.
In order to mimic the direct effect of ionizing radiation on DNA, deoxygenated aqueous solutions of potassium peroxodisulphate, tert-butanol and 1,3,6-trimethyluracil (1,3,6-Me3 U) or 1,3-dimethylthymine (1,3-Me2 T) were irradiated with 60Co gamma rays; the sulphate radical formed by the reaction of the solvated electron with peroxodisulphate oxidizes these pyrimidines. In the case of 1,3,6-Me3 U, a chain reaction results in the formation of sulphuric acid, the glycols (two thirds) and 1,3,6-trimethylisobarbituric acid (one third). Typically, at 5 x 10(-4) mol dm-3 1,3,6-Me3 U, 4 x 10(-2) mol dm-3 S2O8(2-) and 10(-2) mol dm-3 tert-BuOH with a dose-rate of 2.2 x 10(-3) Gy s-1, G(H+) is 220 x 10(-7) mol J-1. We believe that the sulphate radical adds to the 1,3,6-Me3 U and the adduct rapidly loses the sulphate dianion, giving rise to the 1,3,6-Me3 U radical cation. This reacts with water, yielding a proton and the reducing 1,3,6-Me3U C(5)-OH,C(6)-yl radical, which reacts with peroxodisulphate and so propagates the chain. In this oxidation process a carbocation is formed which can either react with water yielding the glycols, or deprotonate yielding the 1,3,6-trimethylisobarbituric acid. The 1,3-Me2 T system behaves differently. No chain reaction of any significance is induced. In the presence of oxygen an allyl-type radical can be trapped, as shown by the subsequent formation of 1,3-dimethyl-5-formyluracil (G = 2.1 x 10(-7) mol J-1) and 1,3-dimethyl-5-hydroxymethyluracil (G = 0.2 x 10(-7) mol J-1). As the corresponding products are not observed in the 1,3,6-Me3 U system, it is concluded that in contrast to the 1,3,6-Me3 U radical cation, the 1,3-Me2 T radical cation efficiently deprotonates (at C5-methyl), apart from also being able to react with water. In basic solution, OH- adds to the 1,3-Me2 T radical cation, thereby suppressing the formation of the allyl-type radical. Quantum-chemical model calculations on uracil, thymine and 6-methyluracil show why 1,3-Me2 T and 1,3,6-Me3 U should differ in their behaviour.(ABSTRACT TRUNCATED AT 250 WORDS)
The purpose of this study was to fabricate a triple-component nanocomposite system consisting of chitosan, polyethylene glycol (PEG), and drug for assessing the application of chitosan-PEG nanocomposites in drug delivery and also to assess the effect of different molecular weights of PEG on nanocomposite characteristics. The casting/solvent evaporation method was used to prepare chitosan-PEG nanocomposite films incorporating piroxicam-β-cyclodextrin. In order to characterize the morphology and structure of nanocomposites, X-ray diffraction technique, scanning electron microscopy, thermogravimetric analysis, and Fourier transmission infrared spectroscopy were used. Drug content uniformity test, swelling studies, water content, erosion studies, dissolution studies, and anti-inflammatory activity were also performed. The permeation studies across rat skin were also performed on nanocomposite films using Franz diffusion cell. The release behavior of films was found to be sensitive to pH and ionic strength of release medium. The maximum swelling ratio and water content was found in HCl buffer pH 1.2 as compared to acetate buffer of pH 4.5 and phosphate buffer pH 7.4. The release rate constants obtained from kinetic modeling and flux values of ex vivo permeation studies showed that release of piroxicam-β-cyclodextrin increased with an increase in concentration of PEG. The formulation F10 containing 75% concentration of PEG showed the highest swelling ratio (3.42±0.02) in HCl buffer pH 1.2, water content (47.89±1.53%) in HCl buffer pH 1.2, maximum cumulative drug permeation through rat skin (2405.15±10.97 μg/cm) in phosphate buffer pH 7.4, and in vitro drug release (35.51±0.26%) in sequential pH change mediums, and showed a significantly (p<0.0001) higher anti-inflammatory effect (0.4 cm). It can be concluded from the results that film composition had a particular impact on drug release properties. The different molecular weights of PEG have a strong influence on swelling, drug release, and permeation rate. The developed films can act as successful drug delivery approach for localized drug delivery through the skin.
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