Vishnu Dutt Sharma

Heterocyclic cationic gemini surfactants: a comparative overview of their synthesis, self-assembling, physicochemical, and biological properties.

Gemini surfactants (GS) are presently receiving substantial attention due to their special self‐assembling properties and unique interfacial activity. This comprehensive review is focused on positively charged heterocyclic GS, presenting their major synthetic access routes and examining the impact of structural elements on physicochemical and aggregation properties of this class of amphiphiles. Interaction of geminis surfactants with cells and their biological properties as novel transfection agents are emphasized through a detailed structure–activity relationship analysis. Throughout the review we have also presented the properties of selected ammonium GS, simple surfactants and lipid congeners, in order to emphasize the advantages conferred by using heterocyclic polar heads in GS design.

Modulation of pyridinium cationic lipid-DNA complex properties by pyridinium gemini surfactants and its impact on lipoplex transfection properties.

The study presents the effects of blending a cationic gemini surfactant into cationic lipid bilayers and its impact on the plasmid DNA compaction and delivery process. Using nanoDSC, dynamic light scattering, zeta potential, and electrophoretic mobility measurements, together with transfection (2D- and 3D-) and viability assays, we identified the main physicochemical parameters of the lipid bilayers, liposomes, and lipoplexes that are affected by the gemini surfactant addition. We also correlated the cationic bilayer composition with the dynamics of the DNA compaction process and with transfection efficiency, cytotoxicity, and the internalization mechanism of the resultant nucleic acid complexes. We found that the blending of gemini surfactant into the cationic bilayers fluidized the supramolecular assemblies, reduced the amount of positive charge required to fully compact the plasmid DNA and, in certain cases, changed the internalization mechanism of the lipoplexes. The transfection efficiency of select ternary lipoplexes derived from cationic gemini surfactants and lipids was several times superior to the transfection efficiency of corresponding binary lipoplexes, also surpassing standard transfection systems. The overall impact of gemini surfactants into the formation and dynamic of cationic bilayers was found to depend heavily on the presence of colipids, their nature, and amount present in lipoplexes. The study confirmed the possibility of combining the specific properties of pyridinium gemini surfactants and cationic lipids synergistically to obtain efficient synthetic transfection systems with negligible cytotoxicity useful for therapeutic gene delivery.

Interfacial engineering of pyridinium gemini surfactants for the generation of synthetic transfection systems.

Pyridinium gemini surfactants possess a soft charge, a high charge/mass ratio and a high molecular flexibility - all key parameters that recommend their use in synthetic gene delivery systems with in vitro and in vivo efficiency. In present study we generated a DNA delivery system through interfacial engineering of pyridinium gemini surfactants at the level of linker, hydrophobic chains and counterions. The self-assembling of the pyridinium amphiphiles and the physicochemical properties of the resultant supra-molecular assemblies were studied in bulk and in solution through a combination of techniques that included DSC, X-ray diffraction, polarized microscopy, CMC, dynamic light scattering and zeta potential measurements. We assessed the impact of different structural elements and formulation parameters of these pyridinium amphiphiles on their DNA compaction properties, transfection efficiency, cytotoxicity, in a complete structure-activity relationship study. This interfacial engineering process generated transfection systems with reduced cytotoxicity and high transfection efficiency in media containing elevated levels of serum that mimic the in vivo conditions.

Solid-State Interactions at the Core-Coat Interface: Physicochemical Characterization of Enteric-Coated Omeprazole Pellets Without a Protective Sub-Coat

Conventionally, scanning electron or transmission microscopy, Raman and near infrared (NIR) spectroscopy, terahertz, florescence, and nuclear magnetic resonance imaging have been used to characterize functional coating structure. This study highlights the use of fluorescence microscopy to investigate the physicochemical stability and coating integrity of the commercially available enteric-coated omeprazole pellets containing a basic excipient and prepared by extrusion and spheronization or drug layering on the nonpareil seed, immediately followed by enteric coating (i.e., absence of protective sub-coat). The nature of coating interface and the likely development of an in situ interfacial layer after the application of enteric coating solution was examined using HPLC, NMR, differential scanning calorimetry (DSC), and fluorescent imaging methods. Likewise for the characterization of the solid pellet structure via fluorescence microscopy, a new approach based on fracturing technique (to avoid surface contamination) rather than microtome sectioning was used and validated. Analytical data showed that the pellets containing omeprazole remained chemically stable (>99.5% recovered). Control of the microenvironmental pH by the addition of alkalinizing excipient within a core formulation or as part of drug layering on top of nonpareil seed appears to efficiently neutralize the acidic effect of enteric coating dispersion. Fluorescence images further illustrate the absence of any discernable in situ layer formation at the coat-core interface.