Pharmaceutical Particulates and Membranes for Delivery of Drugs and Bioactive Molecules

This book is a collection of papers published in the Special Issue of Pharmaceutics, entitled "Pharmaceutical Particulates and Membranes for Delivery of Drugs and Bioactive Molecules". A drug release profile is a consequential factor for nanoparticle application, directly related to drug stability and therapeutic results, as well as formulation development. Pharmaceutical particulates of different sizes and shapes (e.g., liposomes, oil-in-water emulsions, polymeric nano- and microspheres, metallic nanoparticles (NPs) such as gold, silver and iron oxide crystals, and core-shell hybrid NPs) offer many diagnostic and therapeutic applications. Membranes are also extensively utilized in many applications. They are especially beneficial to the distribution of macromolecular drugs and biopharmaceutical drugs (peptides, proteins, antibodies, oligonucleotides, plasmids, and viruses) with physicochemical and pharmacokinetic vulnerability. The delivery of drugs and bioactive molecules using particulates and membranes has gained a great deal of attention for various applications, such as the treatment of secondary infections, cancer treatment, skin regeneration, orthopaedic applications, and antimicrobial drug delivery. In addition, several production techniques have been utilized for the fabrication of particulates and membranes in the last decade, which include lyophilisation, micro-emulsion, nano-spray dryer, nano-electrospinning, slip casting and 3D printers. Therefore, pharmaceutical particulates and membranes possess excellent prospects to deliver drugs and bioactive molecules with the potential to improve new delivery strategies like sustained and controlled release

Single Particle Tracking of Plasma Membrane Proteins.

Palmitoylation is important to the function and trafficking of many proteins. As the only reversible posttranslational lipid modification, it is thought to facilitate signaling by dynamically targeting proteins to the necessary membrane fractions. This has been shown for membrane-associated proteins, but the role of palmitoylation for transmembrane proteins is less clear. It has been proposed that palmitoylation targets transmembrane proteins to membrane subdomains often termed ‘lipid rafts’. In this work, we test the hypothesis that palmitoylation affects the diffusion dynamics of transmembrane proteins and propose that this could be a means to modulate protein function. Using single fluorescent particle tracking, this work quantifies diffusion and confinement parameters of a large panel of fluorescent fusion membrane proteins ranging in size, mode of membrane anchoring, and putative phase-association. These include palmitoylated and non-palmitoylated versions of three transmembrane proteins (truncated linker of activated T-cell, truncated hemagglutinin, and β2 adrenergic receptor) as well as three proteins anchored with lipid moieties (glycophosphatidylinositol (GPI), palmitoyl and myristoyl, or geranylgeranyl). We present a method of analysis that uses Brownian simulations to aid in identifying heterogeneity. Among our findings is that lateral diffusion in a photoprotective hypoxic imaging buffer is Brownian and vastly simplified in comparison to non-hypoxic imaging buffer, suggesting possible cytoskeletal remodeling under hypoxic conditions. In both hypoxic or normoxic imaging conditions, lateral diffusion is strongly size-dependent for smaller probes, consistent with findings in model membranes. Thus our results indicate that diffusion of small probes is particularly sensitive to dimerization when it occurs in either a biological context or due to labeling techniques. Differences in lateral diffusion were not significant at 37°C when comparing otherwise identical transmembrane proteins with and without palmitoylation sites, though the proteins differentiate themselves at lower temperatures. This suggests that palmitoylation does not modulate transmembrane protein function by altering lateral diffusion under physiological conditions.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/107057/1/edwald_1.pd