Experimental design in formulation optimization of vitamin K1 oxide-loaded nanoliposomes for skin delivery.

Due to the vitamin K1 sensitizing potential, the oxidized-isoform of vitamin K1 (vitamin K1 oxide, VKO), has been recently used for treating laser-induced purpura and hyperpigmentation in cosmetics. The objective of this study was to formulate VKO in nanoliposomes by using Box-Behnken experimental design to obtain an optimized formula with higher efficiency. The ratio of phospholipid to cholesterol (PC/CHO ratio), VKO concentration and sonication time in low, medium, and high levels were independent variables, while the percent of VKO entrapment efficiency (EE%) and vesicle size were selected as dependent variables. Optimum desirability was identified and an optimized formulation was prepared, characterized, and selected for in vitro VKO release and ex vivo skin permeation. The PC/CHO ratio showed the greatest effect on both responses (P < 0.0001). This effect was positive on EE%, while a negative effect was shown on vesicle size. The optimized formulation showed controlled drug release of 79.2% through a silicon membrane, and achieved flux of 327.36 ± 22.1 µg/cm2 through human skin after 24 h. So, nanoliposomes were proven as a suitable drug delivery system for topical delivery of VKO.

Mesoporous silica nanoparticles for enhanced lidocaine skin delivery.

Lidocaine's (Lido) low water solubility and negligible tissue uptake limit its bioavailability when applied to the skin. Nanoparticulate systems would help address these issues; therefore, lidocaine inclusion complexes with mesoporous silica nanoparticles (MSNs) were prepared and the effect of MCM41 surface functionalization with positively charged amino-propyl groups on the molecule properties studied. It is expected that positively charged nanoparticles can improve lidocaine permeation into the skin. The complexes were prepared in different lidocaine/MSNs ratios (3/1, 2/1, 1/1) and characterized by X-ray powder diffraction (XRD), dynamic light scattering (DLS) and differential scanning calorimetry (DSC). Fourier transform infrared (FTIR) spectroscopy provided detailed information regarding the molecular interaction of lidocaine with the inorganic surface. The optimized lidocaine-loaded MSNs (1/1) were used for in vitro release studies using dialysis membrane and ex vivo permeation studies by Franz diffusion cell. Higher drug release and skin permeation were observed for the functionalized complex over pure lidocaine and Lido/MCM41 which can be attributed to the electrostatic interaction between positively charged lido/MCM41-NH2 and negatively charged skin membrane cells. Therefore, MCM41-NH2 exhibited superiority over MCM41 and the free drug, suggesting the significance of functionalization in lidocaine dermal delivery.

Nanodiamond applications in skin preparations.

The biocompatibility and nontoxicity of nanodiamonds (NDs) in combination with their excellent physical performance have rendered them attractive candidates for biomedical applications. NDs have great potential in drug nanoformulations because of their small size compared with other carbon nanomaterials. They are nontoxic with excellent adsorption properties and can be formulated into skin care products. Even though NDs have shown encouraging potential in skin preparations, only a few studies have reviewed their application in topical drug delivery systems. Therefore, here we focus on the application of NDs in skin care preparations, skin cancer medication, and wound healing. We also highlight the development of topical drug delivery by NDs and their cytotoxicity.

RNA Loading on Nano-Structured Hyperbranched ß-Cyclodextrin.

BACKGROUND: ß-Cyclodextrin functionalized hyper-branched polyglycerol (HBCD: ß-CD-g-PG), a biocompatible polymer, has recently been proposed for delivery of poorly water soluble compounds. METHODS: The present study examines the interaction of HBCD with RNA, utilizing a constant concentration of RNA and different HBCD/RNA ratios of 1/16 to 1/1, at physiological condition in an aqueous solution. Circular Dichroism (CD), UV-visible, FTIR spectroscopic methods, zeta potential and Dynamic Light Scattering (DLS) were used to analyze the particle formation, particle charge, particle size, aggregation, RNA conformation, binding constant and mode, and the effect of polymer complexation on RNA stability. RESULTS: The results indicate that the interaction of RNA with HBCD leads to the formation of a linear dendritic supramolecule biopolymer with an overall binding constant of KHBCD/RNA= 1.25 × 103. CONCLUSION: The small sized synthesized polymer can be considered as an appropriate system for preventing RNA aggregation and protecting the gene by host-guest interaction.

Fullerene nanoparticle in dermatological and cosmetic applications.

Nanoparticles are equipped with exceptional properties which make them well suitable for diverse and novel applications. Fullerene is one of the nanomaterials that has valuable applications in the field of biomedicine. It possesses exceptional antioxidant capacity which has made it a promising core ingredient in many dermatological and skin care products. However, fullerene has the potentials to display a range of activities resulting in cell death or dysfunction. This review outlines the achievements made so far by reporting studies that have focused on incorporating fullerene in skin care products and cosmetics and assessed their beneficial effects. We have also documented reports that have assessed toxicity of this novel carbon allotrope toward skin cells and discussed its possible dermal reactions. Aside from pointing out the recent developments, areas that can benefit from further researches are identified.

New Generation of Fluconazole: A Review on Existing Researches and Technologies.

BACKGROUND: The frontline drug fluconazole (FLZ) has been used for treating skin fungal infections for over 35 years. FLZ has relatively large molecular size and hydrophobicity which improves its bioavailability via intravenous or oral routes but makes its use in a topical application problematic. In recent years, nano-based strategies have been examined to eliminate FLZ adverse effects and increase the drug efficiency. The present overview surveys nano-drug delivery systems used to improve FLZ efficiency; the strengths and weaknesses of the systems and the relevant achievements of pharmaceutical technology follow. METHODS: A systematic literature search study was developed based on the significant concepts being used in the review. Key search terms and a matrix-based search strategy using Boolean logic strategy were defined. Nano-formulations affecting dermal permeation of nanomaterials and experimental setups for studying skin absorbance of FLZ-nanomaterials were analysed. RESULTS: In recent years, nano-based strategies including solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs), liposomes, niosomes, ethosomes, microemulsions, nanoemulsions have been examined to increase FLZ antifungal efficiency and eliminate drug adverse effects. Significant differences was demonstrated in FLZ efficiency by different nanoparticles. Few data are available regarding a comparison of FLZ antifungal effects using various nanoparticles, but the present research suggests a positive impact on penetration. CONCLUSION: Various nano-formulations have been applied to optimize fluconazole topical delivery. The present review indicated that the data related to improve fluconazole efficacy by nanoparticles are few and defining the appropriate nano-formulation is not currently possible. More research is needed to compare the capability of various nanoparticles on fluconazole skin permeation, and to translate these findings into clinical arena.

Nano-Sized Technologies for Miconazole Skin Delivery.

Various nano-based strategies for increasing the efficiency of topical drugs have offered the potential advantage of miconazole skin delivery. Miconazole nitrate is an antifungal drug with a drawback of poor skin-penetration in the treatment of deep seated fungal skin infections. Drug entrapment in nanoparticles such as ethosome, liposomes, solid lipid nanoparticles (SLNs) and nano structured lipid carriers (NLCs) can facilitate localized drug delivery and remove the skin barriers for an efficient drug delivery. Different nano-formulations have been recently examined for the controlled release, retention and permeation enhancement of miconazole in skin. The present overview focuses on novel nano-based formulation approaches employed to improve miconazole penetration through skin for the treatment of fungal infections.

Novel drug delivery strategies for improving econazole antifungal action.

Econazole is a commonly used azole antifungal in clinical treatment of superficial fungal infections. It is generally used as conventional cream and gel preparations under the brand names of Spectazole (United States), Ecostatin (Canada), Pevaryl (Western Europe). Treatment efficiency of antifungal drugs depends on their penetration through target layers of skin at effective concentrations. Econazole's poor water solubility limits its bioavailability and antifungal effects. Therefore, formulation strategies have been examined for delivering econazole through targeted skin sites. The present overview focuses on novel nano-based formulation approaches used to improve econazole penetration through skin for treatment of superficial fungal infections.

Interaction of sulforaphane with DNA and RNA.

Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables with anti-inflammatory, anti-oxidant and anti-cancer activities. However, the antioxidant and anticancer mechanism of sulforaphane is not well understood. In the present research, we reported binding modes, binding constants and stability of SFN-DNA and -RNA complexes by Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods. Spectroscopic evidence showed DNA intercalation with some degree of groove binding. SFN binds minor and major grooves of DNA and backbone phosphate (PO2), while RNA binding is through G, U, A bases with some degree of SFN-phosphate (PO2) interaction. Overall binding constants were estimated to be K(SFN-DNA)=3.01 (± 0.035)×10(4) M(-1) and K(SFN-RNA)= 6.63 (±0.042)×10(3) M(-1). At high SFN concentration (SFN/RNA = 1/1), DNA conformation changed from B to A occurred, while RNA remained in A-family structure.

Arsenic trioxide binding to serum proteins.

Arsenic trioxide (ATO) also known as Trisenox, is an anticancer chemotherapeutic drug which has been used in treating diagnosed and relapsed patients with acute promyelocytic leukemia (APL). Serum albumin is the most abundant of the proteins in blood plasma and is the major transporter for delivering several drugs in vivo. The current study was designed to evaluate the potential ability of human and bovine serum albumin for delivering arsenic trioxide. Therefore, interaction of arsenic trioxide with HSA and BSA was investigated in aqueous solution at physiological conditions using a constant protein concentration and various drug contents. FTIR and UV-Vis spectroscopic methods were used to analyze arsenic trioxide and protein binding modes, the binding constants and the effect of drug complexation on HSA and BSA stability and conformation. Results of this study showed that drug complexation altered protein conformation by major reduction of α-helix and increase of turn structure which is indicative of a partial protein destabilization. Structural analysis revealed that arsenic trioxide bind HSA and BSA with overall binding constants of KATO-HSA=1.07 (±0.01)×10(4) M(-1) and KATO-BSA=1.27(±0.02)×10(4) M(-1). It could be concluded that serum albumins can be considered as good carriers for delivering arsenic trioxide to target tissue.

Perspectives on percutaneous penetration: Silica nanoparticles.

Nanotechnology is a rapidly expanding area of research involved in developing science-based solutions for innovative therapeutics. Silica nanoparticles (SNPs) have received wide attention in several industries and medicine and are being developed for biomedical and biotechnological applications such as drug delivery, DNA transfection, and targeted molecular imaging of cancer. Recently, they are emerging in the fields of cosmetics and dermal preparations. SNP may offer a revolutionized treatment of several skin diseases by controlled and sustained release of drugs to skin, as well as enhanced skin penetration of encapsulated drug ingredients. SNPs are candidates for transcutaneous vaccination and transdermal gene therapy, too. Yet there exist concerns that whilst the properties of SNPs have enabled numerous industrial and medical applications, their toxicological and environmental safety mandates evaluation. The knowledge of passage of SNPs through skin following skin exposure (intentionally or unintentionally) and subsequent effects is limited. This review surveys the key experiments on SNP-based formulations in the fields of dermatology and cosmetics with the goal of rationalizing data and informing public health concerns related to SNPs' toxicity among scientists and manufacturers handling them, while highlights the research gaps in dermal absorption of these compounds.

Adsorption properties of tetracycline onto graphene oxide: equilibrium, kinetic and thermodynamic studies.

Graphene oxide (GO) nanoparticle is a high potential effective absorbent. Tetracycline (TC) is a broad-spectrum antibiotic produced, indicated for use against many bacterial infections. In the present research, a systematic study of the adsorption and release process of tetracycline on GO was performed by varying pH, sorption time and temperature. The results of our studies showed that tetracycline strongly loads on the GO surface via π-π interaction and cation-π bonding. Investigation of TC adsorption kinetics showed that the equilibrium was reached within 15 min following the pseudo-second-order model with observed rate constants of k2 = 0.2742-0.5362 g/mg min (at different temperatures). The sorption data has interpreted by the Langmuir model with the maximum adsorption of 323 mg/g (298 K). The mean energy of adsorption was determined 1.83 kJ/mol (298 K) based on the Dubinin-Radushkevich (D-R) adsorption isotherm. Moreover, the thermodynamic parameters such as ΔH°, ΔS° and ΔG° values for the adsorption were estimated which indicated the endothermic and spontaneous nature of the sorption process. The electrochemistry approved an ideal reaction for the adsorption under electrodic process. Simulation of GO and TC was done by LAMMPS. Force studies in z direction showed that tetracycline comes close to GO sheet by C8 direction. Then it goes far and turns and again comes close from amine group to the GO sheet.

Study on the interaction of homoisoflavonoids with RNA.

Homoisoflavonoids (3-benzylidene-4-chromanones) are isomers of flavonoids and exhibit different biological activities because of hydroxyl groups attaching to different positions. This study is the first attempt to locate the binding sites of four synthetic homoisoflavonoids: (E)-3-(3,4-dihydroxybenzylidene)-7-methoxychroman-4-one (BMC), (E)-3-(3,4-dihydroxybenzylidene)-7-propoxychroman-4-one (BPC), (E)-3-(4-hydroxybenzylidene)-7-methoxychroman-4-one (HBMC) and (E) 3-(4-hydroxybenzylidene)-chroman-4-one (HBC) to RNA. The effect of the ligand complexation on RNA aggregation was investigated in aqueous solution at physiological conditions, using constant RNA concentration (6.25mM) and various ligand/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, 1/10 and 1/5. Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of ligand-RNA complexes in aqueous solution. Spectroscopic evidence showed external binding of homoisoflavonoids to RNA duplex with overall binding constants of KBMC-RNA = 1.06(± 0.09) × 10(4)M(-1), KBPC-RNA = 1.11(± 0.15) × 10(4)M (-1), KHBC-RNA = 3.82(± 0.09) × 10(3)M(-1) and KHBMC-RNA=5.82(± 0.04) × 10(3) M(-1). The affinity of homoisoflavonoid-RNA binding is in the order of BPC>BMC>HBMC>HBC. No biopolymer secondary structural changes were observed upon homoisoflavonoids interaction and RNA remains in the A-family structure in these complexes.

Encapsulation of milk ß-lactoglobulin by chitosan nanoparticles.

Naturally occurring polymers, such as chitosan, have been extensively studied as carriers for therapeutic protein and gene delivery systems. ß-Lactoglobulin (ß-LG) is a member of the lipocalin superfamily of transporters for small hydrophobic molecules. We examine the binding of milk ß-lactoglobulin with chitosan of different sizes such as chitosan 15, 100, and 200 KD in aqueous solution at pH 5-6, using FTIR, CD, and fluorescence spectroscopic methods. Structural analysis showed that chitosan binds ß-LG via both hydrophilic and hydrophobic contacts with overall binding constants of K(ß-LG-ch-15) = 4.1 (±0.4) × 10(2) M(-1), K(ß-LG-ch-100) = 7.2 (±0.6) × 10(4) M(-1), and K(ß-LG-ch-200) = 3.9 (±0.5) × 10(3) M(-1) with the number of bound protein per chitosan (n) 0.9 for ch-15, 0.6 for ch-100, and 1.6 for ch-200. Chitosan 100 KD forms stronger complexes with ß-LG than chitosans 200 and 15 KD. Polymer binding did not alter protein conformation inducing structural stabilization. Chitosan 100 is a stronger protein transporter than chitosan 15 and 200 KD.

Study on the interaction of sulforaphane with human and bovine serum albumins.

Sulforaphane; [1-isothiocyanato-4-(methylsulfinyl) butane], (SFN) is an isothiocyanate derived from glucoraphanin present in cruciferous vegetables and has a variety of potential chemopreventive actions. This study was designed to examine the interaction of sulforaphane with HSA and BSA. FTIR, UV-Vis spectroscopic methods as well as molecular modeling were used to determine the drug binding mode, binding constant and the effect of drug complexation on serum albumins stability and conformation. Structural analysis showed that SFN bind HSA and BSA via polypeptide polar groups with overall binding constants of KSFN-HSA=6.54×10(4) and KSFN-BSA=8.55×10(4) M(-1). HSA and BSA conformations were altered by a major reduction of α-helix upon SFN interaction. These results suggest that serum albumins might act as carrier proteins for SFN in delivering them to target tissues.

A comparative study of the interaction of Tamiflu and Oseltamivir carboxylate with bovine serum albumin.

Oseltamivir phosphate (Tamiflu) is a pro-drug that is metabolized to its active form (Oseltamivir carboxylate), after oral administration. OC inhibits influenza A and B neuraminidases in vitro and OP inhibits influenza virus infection and replication in vitro. Serum albumin is the most abundant of the proteins in the circulatory system of a wide variety of organisms and plays an important role in the transport and deposition of many drugs. The aim of this study was to examine the interaction of BSA with Tamiflu and Oseltamivir carboxylate in aqueous solution at physiological conditions, using a constant protein concentration and various drug contents. FTIR, UV-Vis spectroscopic methods were used to determine the drugs binding mode, the binding constant and the effects of drug complexation on protein secondary structure. Structural analysis showed that OP and OC bind BSA with overall binding constants of K(OP-BSA)=1.88 (±0.16)×10(4)M(-1) and K(OC-BSA)=5.7 (±0.09)×10(2)M(-1). Drug complexation alters protein conformation by major reduction of α-helix and random coil and increase of ß-sheet and turn structures that indicate a partial protein destabilization. The results suggest that BSA might act as carrier proteins for OP in delivering it to target molecules.

Molecular aspects on the specific interaction of homoisoflavonoids to DNA.

Homoisoflavonoids (3-benzylidenechroman-4-ones) are related to flavonoids and occur as natural products and exhibit biological activity. These compounds have been reported to possess antioxidant, antifungal, hypocholesterolemic, antimutagenic and antiviral activities. This study was designed to examine the interactions of four synthetic homoisoflavonoids (BMC, BPC, HBC and HBMC) with calf-thymus DNA in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various homoisoflavonoids/polynucleotide (phosphate) ratios of 1/120, 1/80, 1/40, 1/20, 1/10 and 1/5. Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods were used to determine the ligand binding modes, the binding constants and the stability of homoisoflavonoids-DNA complexes in aqueous solution. Spectroscopic evidence showed major binding of homoisoflavonoids to DNA with overall binding constants of K(BMC-DNA)=9.37(± 0.34)× 10(3)M(-1), K(BPC-DNA)=1.8(± 0.09)× 10(4)M(-1), K(HBC-DNA)=1.3(± 0.19)× 10(3)M(-1) and K(HBMC-DNA)=4.7(± 0.41)× 10(3)M(-1). The affinity of homoisoflavonoids-DNA binding is in the order of BPC>BMC>HBMC>HBC. No biopolymer secondary structural changes were observed upon homoisoflavonoids interaction and DNA remains in the B-family structure in these complexes.

The effect of Se salts on DNA structure.

There is considerable interest in the role of selenium in cancer prevention. Various organic and inorganic Se compounds are considered to be antioxidants. In the present study, the binding modes, the binding constants and the stability of Se-DNA complexes have been determined by Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods. Spectroscopic evidence showed that Na(2)SeO(4) and Na(2)SeO(3) bind to the minor and major grooves of DNA and the backbone phosphate (PO(2)) with overall binding constants of K(Na(2)SeO(4)-DNA)=5.20×10(4) M(-1) and K(Na(2)SeO(3)-DNA)=1.87×10(3) M(-1). DNA aggregations occurred at high selenium concentrations. No biopolymer conformational changes were observed upon Na(2)SeO(3) and Na(2)SeO(4) interactions, while DNA remained in the B-family structure.

Study on the interaction of glycyrrhizin and glycyrrhetinic acid with RNA.

Glycyrrhizin is a well known pharmacologically bioactive natural glycoside. Glycyrrhizin (GL) has been widely used as a therapeutic agent for chronic active liver diseases. Glycyrrhetinic acid is an aglycone and an active metabolite of glycyrrhizin. This study is the first attempt to locate the binding sites of glycyrrhizin and glycyrrhetinic acid to RNA. The effect of the ligand complexation on RNA aggregation was investigated in aqueous solution at physiological conditions, using constant RNA concentration (6.25 mM) and various ligand/polynucleotide (phosphate) ratios of 1/280, 1/240, 1/120, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2 and 1/1. Fourier transform infrared (FTIR) and UV-Visible spectroscopic methods as well as molecular modeling were used to determine the ligand binding modes, the binding constants, and the stability of ligands-RNA complexes in aqueous solution. Spectroscopic evidence showed that glycyrrhizin and glycyrrhetinic acid bind RNA via G-C and A-U base pairs as well as the backbone phosphate group with overall binding constants of K(GL-RNA)=3.03×10(3)M(-1), K(GA-RNA)=2.71×10(3)M(-1). The affinity of ligands-RNA binding is in the order of glycyrrhizin>glycyrrhetinic acid. RNA remains in the A-family structure, while biopolymer aggregation occurred at high triterpenoid concentrations.

Interaction of glycyrrhizin and glycyrrhetinic acid with DNA.

Glycyrrhizin (GL), a molecule of glycyrrhetinic acid (GA), is an aqueous extract from licorice root. These compounds are well known for their anti-inflammatory, hepatocarcinogenesis, antiviral, and interferon-inducing activities. This study is the first attempt to investigate the binding of GL and GA with DNA. The effect of ligand complexation on DNA aggregation and condensation was investigated in aqueous solution at physiological conditions, using constant DNA concentration (6.25 mM) and various ligands/polynucleotide (phosphate) ratios of 1/240, 1/120, 1/80, 1/40, 1/20, 1/10, 1/5, 1/2, and 1/1. Fourier transform infrared and ultraviolet (UV)-visible spectroscopic methods were used to determine the ligand binding modes, the binding constants, and the stability of ligand-DNA complexes in aqueous solution. Spectroscopic evidence showed that GL and GA bind DNA via major and minor grooves as well as the backbone phosphate group with overall binding constants of K(GL-DNA)=5.7×10(3) M(-1), K(GA-DNA)=5.1×10(3) M(-1). The affinity of ligand-DNA binding is in the order of GL>GA. DNA remained in the B-family structure, whereas biopolymer aggregation occurred at high triterpenoid concentrations.