Nanoscale Structure of Lipid-Gemini Surfactant Mixed Monolayers Resolved with AFM and KPFM Microscopy.

Drug delivery vehicles composed of lipids and gemini surfactants (GS) are promising in gene therapy. Tuning the composition and properties of the delivery vehicle is important for the efficient load and delivery of DNA fragments (genes). In this paper, we studied novel gene delivery systems composed of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl--3-phosphocholine (DPPC), and GS of the type N,N-bis(dimethylalkyl)-α,ω-alkanediammonium dibromide at different ratios.

Defect-Rich MoSe 2H/1T Hybrid Nanoparticles Prepared from Femtosecond Laser Ablation in Liquid and Their Enhanced Photothermal Conversion Efficiencies.

MoSe 2H/1T hybrid nanoparticles are prepared by femtosecond laser ablation of MoSe powder in isopropyl alcohol with different laser powers and ablation times, and their formation mechanisms and photothermal conversion efficiencies (PTCEs) are studied. Two types of spherical nanoparticles are observed. The first type is onion-structured nanoparticles that are formed by nucleation on the surfaces of melted droplets followed by inward growth of {002} planes of MoSe .

An Overview of Nanotechnologies for Drug Delivery to the Brain.

Drug delivery to the brain has been one of the toughest challenges researchers have faced to develop effective treatments for brain diseases. Owing to the blood-brain barrier (BBB), only a small portion of administered drug can reach the brain. A consequence of that is the need to administer a higher dose of the drug, which, expectedly, leads to a variety of unwanted side effects.

Challenges of Dissolution Methods Development for Soft Gelatin Capsules.

Recently, the development of soft gelatin capsules (SGCs) dosage forms has attracted a great deal of interest in the oral delivery of poorly water-soluble drugs. This is attributed to the increased number of poorly soluble drugs in the pipeline, and hence the challenges of finding innovative ways of developing bioavailable and stable dosage forms. Encapsulation of these drugs into SGCs is one of the approaches that is utilized to deliver the active ingredients to the systemic circulation to overcome certain formulation hurdles.

Kelvin probe force microscopy to study electrostatic interactions of DNA with lipid-gemini surfactant monolayers for gene delivery.

In novel gene therapy mechanisms utilising gemini surfactants, electrostatic interactions of the surfactant molecules with the DNA strands is a primary mechanism by which the two components of the delivery vehicle bind. In this work, we show for the first time direct evidence of electrostatic interactions of these compounds visualised with Kelvin probe force microscopy (KPFM) and correlated to their topography from atomic force microscopy (AFM). We construct monolayers of lipids and gemini surfactant to simulate interactions on a cellular level, using lipids commonly found in cell membranes, and allow DNA to bind to the monolayer as it is formed on a Langmuir-Blodgett trough.

Mixing behaviour of Pluronics with gemini surfactant/plasmid DNA condensates: effect of Pluronic composition.

Nanoparticles prepared from plasmid DNA (pDNA) and N,N-bis(dimethylhexadecyl)-1,3-propanediammonium bromide (16-3-16) have been mixed with various Pluronic block copolymers and investigated as binary surfactant systems in water using the previously demonstrated critical aggregation concentration of the surfactant-DNA complex. Surface tensiometry was used to determine critical micelle concentrations of mixed micelles formed within these Pluronic/16-3-16/pDNA mixtures. Use of mixed micelle theories reveals that mixed micelle composition and the interaction parameter, β, are influenced by the structure, in particular hydrophobicity, of the Pluronic component.

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions.

Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e.

cationic gemini and zwitterionic surfactants - a thermodynamic analysis of their mixed micelle formation.

Micelle formation enthalpies (Δ values) have been calorimetrically determined at 298 K for three sets of mixed zwitterionic/cationic gemini systems consisting of -dodecyl-,-dimethyl-3-ammonio-1-propanesulfonate (ZW3-12) and a series of structurally related gemini surfactants, the ,'-bis(dimethyldodecyl)-α,ω-alkanediammonium dibromide (12--12) systems. From the experimental and the estimated ideal micelle formation enthalpies, the excess enthalpies were obtained. The degrees of nonideality of the interaction in the mixed micelle ( ) from our previous work was used along with the excess enthalpy values to determine excess thermodynamic quantities of the surfactants in the mixed system according to Regular Solution Theory (RST) and Motomura's theory.

Biodistribution and Physiologically-Based Pharmacokinetic Modeling of Gold Nanoparticles in Mice with Interspecies Extrapolation.

Gold nanoparticles (AuNPs) are a focus of growing medical research applications due to their unique chemical, electrical and optical properties. Because of uncertain toxicity, "green" synthesis methods are emerging, using plant extracts to improve biological and environmental compatibility. Here we explore the biodistribution of green AuNPs in mice and prepare a physiologically-based pharmacokinetic (PBPK) model to guide interspecies extrapolation.

Investigating the Phospholipid Effect on the Bioaccessibility of Rosmarinic Acid-Phospholipid Complex through a Dynamic Gastrointestinal in Vitro Model.

Phyto-phospholipid complexes have been developed as a common way of improving the oral bioavailability of poorly absorbable phyto-pharmaceuticals; however, the complexation with phospholipids can induce positive or negative effects on the bioaccessibility of such plant-derived active ingredients in different parts of the gastrointestinal tract (GIT). The purpose of this study was to investigate the effects of phospholipid complexation on the bioaccessibility of a rosmarinic acid-phospholipid complex (RA-PLC) using the TNO dynamic intestinal model-1 (TIM-1). Preparation of RA-PLC was confirmed using X-ray diffraction, Fourier-transform infrared spectroscopy, partition coefficient measurement, and Caco-2 monolayer permeation test.

Continuous Langmuir-Blodgett Deposition and Transfer by Controlled Edge-to-Edge Assembly of Floating 2D Materials.

The Langmuir-Blodgett technique is one of the most controlled methods to deposit monomolecular layers of floating or surface active materials but has lacked the ability to coat truly large-area substrates. In this work, by manipulating single-layer dispersions of graphene oxide (GO) and thermally exfoliated GO into water-immiscible spreading solvents, unlike traditional Langmuir-Blodgett deposition which requires densification achieved by compressing barriers, we demonstrate the ability to control the 2D aggregation and densification behavior of these floating materials using a barrier-free method. This is done by controlling the edge-to-edge interactions through modified subphase conditions and by utilizing the distance-dependent spreading pressure of the deposition solvent.

Non-viral Gene Delivery.

Although viral vectors comprise the majority of gene delivery vectors, their various safety, production, and other practical concerns have left a research gap to be addressed. The non-viral vector space encompasses a growing variety of physical and chemical methods capable of gene delivery into the nuclei of target cells. Major physical methods described in this chapter are microinjection, electroporation, and ballistic injection, magnetofection, sonoporation, optical transfection, and localized hyperthermia.

Modified gelatin nanoparticles for gene delivery.

Gelatin nanoparticles (GNPs) are one of the most extensively used natural polymers for gene therapy. With advantages of being biodegradable, biocompatible, low cost and easily modified, gelatin holds great promise as a non-viral system for gene delivery. This review examines various methods of preparation of modified gelatin nanoparticles and considers how these modifications apply to gene delivery.

Cationic Gemini Surfactant-Plasmid Deoxyribonucleic Acid Condensates as a Single Amphiphilic Entity.

A critical aggregate concentration for the surfactant-DNA "complex" or "condensate" consisting of the 16-3-16 gemini surfactant and circular plasmid DNA was determined using surface tensiometry, dynamic light scattering, and conductometry. This surfactant-DNA complex acts as an amphiphile itself, for example, decreasing the surface tension of water until a critical concentration is reached. The evidence presented here introduces a new way of considering these surfactant-DNA condensates, not simply as aggregates in solution but as surface-active agents in their own right.

Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.

Emulsion technology has been utilized extensively in the pharmaceutical industry. This article presents a comprehensive review of the literature on an important subcategory of emulsions, microemulsions. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that form spontaneously upon mixing of oil, water and emulsifier.

Effect of counterions on the micellization and monolayer behaviour of cationic gemini surfactants.

The effect of various inorganic and organic counterions on the aggregation behavior of gemini surfactants was examined to investigate the dominant influence of the anions on their micellization and aggregation behavior. This study included eight ethanediyl-α,ω-bis-(dimethylhexadecylammonium) gemini surfactants (GS, also known as 16-2-16) having counterions of chloride (Cl), bromide (Br), malate, tartrate, adenosine monophosphate (AMP), guanosine monophosphate (GMP), cytidine monophosphate (CMP), and uridine monophosphate (UMP). Tensiometry, conductivity and Langmuir monolayer measurements were performed to investigate the micellization and surface behaviour of each surfactant.

Synthesis and characterization of asymmetrical gemini surfactants.

The effect of variation in the length of surfactant hydrocarbon tail groups was tested in a series of dissymmetric gemini surfactants (N-alkyl N,N,N,N-tetramethyl-N-(6-pyren-6yl)-hexyl)propane-1,3-diammonium dibromide designated as CCCBr, with m = hexyl pyrene, and n = 8, 12, 14, 16, and 18. The aggregation properties of these surfactants have been investigated by means of H NMR, fluorescence spectroscopy, surface tension and electrical conductivity measurements. The critical micelle concentration (CMC) was determined using surface tension and confirmed using the specific conductance method.

Effect of spacer length on the interfacial behavior of N,N'-bis(dimethylalkyl)-α,ω-alkanediammonium dibromide gemini surfactants in the absence and presence of ZnO nanoparticles.

In this paper the interfacial behavior of aqueous solutions of cationic gemini surfactants of the, N,N'-bis(dimethylalkyl)-α,ω-alkanediammoniumdibromide type (known as the 12-s-12 series), in the absence and presence of ZnO nanoparticles was studied. Equilibrium and dynamic interfacial tension between n-decane and aqueous surfactant solutions were investigated. It was concluded that the synergistic effect between surfactants and nanoparticles increases the surfactant efficiency with respect to reducing the interfacial tension.

Synthesis and evaluation of alendronate-modified gelatin biopolymer as a novel osteotropic nanocarrier for gene therapy.

Aim: To synthesize an osteotropic alendronate functionalized gelatin (ALN-gelatin) biopolymer for nanoparticle preparation and targeted delivery of DNA to osteoblasts for gene therapy applications.

Materials & Methods: Alendronate coupling to gelatin was confirmed using Fourier transform IR, (31)PNMR, x-ray diffraction (XRD) and differential scanning calorimetry. ALN-gelatin biopolymers prepared at various alendronate/gelatin ratios were utilized to prepare nanoparticles and were optimized in combination with DNA and gemini surfactant for transfecting both HEK-293 and MG-63 cell lines.

Interactions between DNA and Gemini surfactant: impact on gene therapy: part I.

Nonviral gene therapy using gemini surfactants is a unique approach to medicine that can be adapted toward the treatment of various diseases. Recently, gemini surfactants have been utilized as candidates for the formation of nonviral vectors. The chemical structure of the surfactant (variations in the alkyl tail length and spacer/head group) and the resulting physicochemical properties of the lipoplexes are critical parameters for efficient gene transfection.

Interactions between DNA and gemini surfactant: impact on gene therapy: part II.

Nonviral gene delivery, provides distinct treatment modalities for the inherited and acquired diseases, relies upon the encapsulation of a gene of interest, which is then ideally delivered to the target cells. Variations in the chemical structure of gemini surfactants and subsequent physicochemical characteristics of the gemini-based lipoplexes and their impact on efficient gene transfection were assessed in part I, which was published in first March 2016 issue of Nanomedicine (1103). In order to design an efficient vector using gemini surfactants, the interaction of the surfactant with DNA and other components of the delivery system must be characterized, and more critically, well understood.

Physical Characterization of Gemini Surfactant-Based Synthetic Vectors for the Delivery of Linear Covalently Closed (LCC) DNA Ministrings.

In combination with novel linear covalently closed (LCC) DNA minivectors, referred to as DNA ministrings, a gemini surfactant-based synthetic vector for gene delivery has been shown to exhibit enhanced delivery and bioavailability while offering a heightened safety profile. Due to topological differences from conventional circular covalently closed (CCC) plasmid DNA vectors, the linear topology of LCC DNA ministrings may present differences with regards to DNA interaction and the physicochemical properties influencing DNA-surfactant interactions in the formulation of lipoplexed particles. In this study, N,N-bis(dimethylhexadecyl)-α,ω-propanediammonium(16-3-16)gemini-based synthetic vectors, incorporating either CCC plasmid or LCC DNA ministrings, were characterized and compared with respect to particle size, zeta potential, DNA encapsulation, DNase sensitivity, and in vitro transgene delivery efficacy.

Synergistic behaviour of ZnO nanoparticles and gemini surfactants on the dynamic and equilibrium oil/water interfacial tension.

In this work the effect of ZnO nanoparticles on the interfacial behaviour of gemini surfactants (12-3-12 and 14-3-14) at the oil/water interface was investigated. Equilibrium and dynamic interfacial tension in the absence and presence of ZnO was measured and compared. The results show that the synergistic interactions between the surfactants and nanoparticles decrease the interfacial tension beyond that observed for each component, alone.

Impact of DNA vector topology on non-viral gene therapeutic safety and efficacy.

Gene therapy continues to grow as an emerging treatment strategy toward numerous diseases. However, such prospects are hindered by the use of viral vectors prompting significant safety concerns along with limitations concerning repeat administrations, size of delivered gene construct, scale-up, high production costs, contamination during production, and lack of desired tissue selectivity. Non-viral gene delivery demonstrates the potential to address the abovementioned limitations, but itself generally suffers from low efficacy.

Separation and purification of linear covalently closed deoxyribonucleic acid by Q-anion exchange membrane chromatography.

We have constructed an in vivo system for rapid, scalable production of linear covalently closed (LCC) DNA from precursor circular covalently closed (CCC) plasmid DNA (pDNA) that offers a stronger safety profile compared to conventional CCC pDNA vectors. In the processing of LCC DNA products from the precursor CCC pDNA, LCC minivector DNA is produced in addition to other precursor DNA species and isoforms. DNA purification by anion exchange chromatography (AEC) attains high vector purity, making it an efficient and valuable approach to purification processes for the production of clinical grade DNA.