Studies of the interaction of gemini surfactants with polymers and triblock copolymers

The interaction of two novel surfactants, known as gemini surfactants, with aqueous solutions of neutral polymers, specifically polyethylene oxide (PEO), polypropylene oxide (PPO), and polyethylene oxide-polypropylene oxide-polyethylene oxide (PEO-PPO-PEO) triblock copolymers, have been investigated. In order to provide a basis for comparison, an investigation of the aqueous solution behaviour of two series of N,N'-bis(alkyldimethyl)-α,[omega]-alkanedianimonium dibromide surfactants was carried out. One series had a constant spacer length (s) of 3 methylene units with various alkyl chain lengths (m) of 8, 10, 12, and 16, and the other had a constant in of 12 with various s between 2 and 16 inclusive. A surfactant with in = 12 and a 'p'-xylyl ([straight phi]) spacer also was studied to assess the effect of rigidity in the spacer group on gemini interfacial properties. The results obtained for the critical micelle concentration (CMC) and head group area (a0) of the surfactants are in excellent agreement with those previously reported. The mean aggregation number of the surfactants decreases with increasing spacer chain length up to s = 8, after which the aggregation number increases. The initial decrease results from a decrease in the surface area available to a surfactant monomer as the area taken up by the spacer group is increased. Experimental apparent molar volume (AMV) data have been modeled assuming both a mass-action model (8-3-8, only) and a pseudo-phase model. The observed variation in the volume change due to micelle formation, [Delta]V[straight phi],M, is consistent with variations in ao and the CMC, and can be rationalized in terms of possible spacer conformations in the aqueous and micellar phases. Results obtained for the 12-[straight phi]-12 surfactant indicate that rigidity of the spacer has no measurable effect on the micellization process for shorter spacer lengths. The interaction of the gemini surfactants with the triblock copolymers in aqueous solution was markedly different from that typically observed in surfactant-polymer systems, and is similar in nature to a solubilization or mixed micelle formation process. The results obtained indicate that the interaction occurs primarily with the PPO segment of the triblock copolymer through a replacement of hydration water by polymer at the micellar surface. The solubility of the surfactant monomer (i.e. the CMC) may be increased through specific interactions between the surfactant and polymeric microdomains in solution. The results of a temperature dependent study indicate that the aggregation state of the copolymer in solution has a significant effect on the interaction with gemini surfactants

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. Research in a variety of different fields has been underway for the past couple of decades to address this very serious and frequently lethal problem. One area of research that has produced optimistic results in recent years is nanomedicine. Nanomedicine is the science birthed by fusing the fields of nanotechnology, chemistry and medicine into one. Many different types of nanomedicine-based drug-delivery systems are currently being studied for the sole purpose of improved drug delivery to the brain. This review puts together and briefly summarizes some of the major breakthroughs in this crusade. Inorganic nanoparticle-based drug-delivery systems, such as gold nanoparticles and magnetic nanoparticles, are discussed, as well as some organic nanoparticulate systems. Amongst the organic drug-delivery nanosystems, polymeric micelles and dendrimers are discussed briefly and solid polymeric nanoparticles are explored in detail

Fluorescence-based techniques to assess the miscibility and physical stability of a drug-lipid complex

The objective of this study was to evaluate the feasibility of using fluorescence-based techniques to assess the miscibility and physical stability of a drug-lipid complex pharmaceutical dosage form under a solvent-free condition. An indomethacin-phospholipid complex (IDM-PLC) was used as model complex for this study. The miscibility of indomethacin within the phospholipid was assessed by fluorescence spectroscopy, fluorescence microscopy and infrared spectroscopy. The miscibility limit of the complex system was determined by fluorescence to be 20-30% drug loading content, showing good correlation with infrared spectroscopy. The physical stability of the indomethacin-phospholipid complex stored at 40â was evaluated by fluorescence microscopy. Indomethacin formulated in the lipid complex with an indomethacin loading not more than 30% remained in an amorphous state within a period of 21 days, while the samples with a drug loading over 30% started to crystallize earlier with increasing drug content. IDM-PLC having higher miscibilities were found to be more resistant to recrystallization under heating, thus having better physical stability. Fluorescence-based techniques showed convenience and promise in characterizing drug-lipid miscibility and predicting storage stability under a solvent-free condition.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

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. Through comparative analysis, differences between CCC plasmid DNA and LCC DNA ministrings led to variations in the physical properties of the resulting lipoplexes after complexation with 16-3-16 gemini surfactants. Despite the size disparities between the plasmid DNA vectors (CCC) and DNA ministrings (LCC), differences in DNA topology resulted in the generation of lipoplexes of comparable particle sizes. The capacity for ministring (LCC) derived lipoplexes to undergo complete counterion release during lipoplex formation contributed to improved DNA encapsulation, protection from DNase degradation, and in vitro transgene delivery

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. Bioaccessibility parameters in different GIT compartments were investigated. Complexation by phospholipids reduced the bioaccessibility of RA in jejunum compartment, while maintaining the ileum bioaccessibility. The overall bioaccessibility of RA-PLC was lower than the unformulated drug, suggesting that the improved oral absorption from a previous animal study could be considered as a net result of decreased bioaccessibility overwhelmed by enhanced intestinal permeability. This study provides insights into the effects of phospholipid on the bioaccessibility of hydrophilic compounds, and analyzes them based on the relationship between bioaccessibility, membrane permeability, and bioavailability. Additionally, TIM-1 shows promise in the evaluation of dosage forms containing materials with complicated effects on bioaccessibility

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. Once formulated, encapsulated drugs in the form of SGCs require suitable in vitro dissolution test methods to ensure drug product quality and performance. This review focuses on challenges facing dissolution test method development for SGCs. A brief discussion of the physicochemical and formulation factors that affect the dissolution properties of SGCs will be highlighted. Likewise, the influence of cross-linking of gelatin on the dissolution properties of SGCs will also be discussed