Enhanced Oral Bioavailability of Progesterone in Bilosome Formulation: Fabrication, Statistical Optimization, and Pharmacokinetic Study.

Progesterone, a female sex steroid hormone, is highly lipophilic, leading to poor oral bioavailability. This study aimed to develop a progesterone bilosome system to enhance its oral bioavailability and retain it longer in the body. Progesterone vesicles were formulated with bile salts by thin film hydration method to prevent enzymatic and bile acid degradation.

Advances in progesterone delivery systems: Still work in progress?

Progesterone is a natural steroidal sex hormone in the human body, mainly secreted through the adrenal cortex, ovary, and placenta. In humans, progesterone is essential for endometrium transformation in the uterus at the time of ovulation and maintenance of pregnancy. When the body cannot produce enough progesterone for specific ailments, it is administered via different routes such as oral, vaginal, transdermal, topical, parental, and intranasal routes.

Design of monodisperse and well-defined polypeptide-based polyvalent inhibitors of anthrax toxin.

The design of polyvalent molecules, presenting multiple copies of a specific ligand, represents a promising strategy to inhibit pathogens and toxins. The ability to control independently the valency and the spacing between ligands would be valuable for elucidating structure-activity relationships and for designing potent polyvalent molecules. To that end, we designed monodisperse polypeptide-based polyvalent inhibitors of anthrax toxin in which multiple copies of an inhibitory toxin-binding peptide were separated by flexible peptide linkers.

Characterization of the oligomerization and aggregation of human Serum Amyloid A.

The fibrillation of Serum Amyloid A (SAA) - a major acute phase protein - is believed to play a role in the disease Amyloid A (AA) Amyloidosis. To better understand the amyloid formation pathway of SAA, we characterized the oligomerization, misfolding, and aggregation of a disease-associated isoform of human SAA - human SAA1.1 (hSAA1.

Influence of the carboxy terminus of serum amyloid A on protein oligomerization, misfolding, and fibril formation.

The fibrillar deposition of serum amyloid A (SAA) has been linked to the disease amyloid A (AA) amyloidosis. We have used the SAA isoform, SAA2.2, from the CE/J mouse strain, as a model system to explore the inherent structural and biophysical properties of SAA.

Manipulation of electrostatic and saccharide linker interactions in the design of efficient glycopolypeptide-based cholera toxin inhibitors.

Multivalent, glycopolymer inhibitors designed for the treatment of disease and pathogen infection have shown improvements in binding correlated with general changes in glycopolymer architecture and composition. We have previously demonstrated that control of glycopolypeptide backbone extension and ligand spacing significantly impacts the inhibition of the cholera toxin B subunit pentamer (CT B(5)) by these polymers. In the studies reported here, we elucidate the role of backbone charge and linker length in modulating the inhibition event.

Polymer-Based Therapeutics.

Polymeric materials have been applied in therapeutic applications, such as drug delivery and tissue regeneration, for decades owing to their biocompatibility and suitable mechanical properties. In addition, select polymer-drug conjugates have been used as bioactive pharmaceuticals owing to their increased drug efficacy, solubility, and target specificity compared with small-molecule drugs. Increased synthetic control of polymer properties has permitted the production of polymer assemblies for the targeted and controlled delivery of drugs, and polymeric sequestrants take advantage of their lack of solubility for the sequestration of target molecules in vivo.

Effects of Saccharide Spacing and Chain Extension on Toxin Inhibition by Glycopolypeptides of Well-Defined Architecture.

Many recognition events important in biology are mediated via multivalent interactions between relevant oligosaccharides and multiple saccharide receptors present on lectins, viruses, toxins, and cell surfaces. Because of the important role played by protein-carbohydrate interactions in these pathogenic recognition events and in other human diseases, considerable effort has been devoted toward the development of multivalent polymeric ligands for carbohydrate-binding proteins. In this work, we report the synthesis of new polypeptide-based glycopolymers produced via a combination of protein engineering and chemical methods.

Conformation and assembly of polypeptide scaffolds in templating the synthesis of silica: an example of a polylysine macromolecular "switch".

Although the role of polycationic macromolecules in catalyzing the synthesis of silica structures is well established, detailed understanding of the mechanisms behind the production of silica structures of controlled morphologies remains unclear. In this study, we have used both poly-L-lysine (PLL) and/or poly-D-lysine (PDL) for silica synthesis to investigate mechanisms controlling inorganic morphologies. The formation of both spherical silica particles and hexagonal plates was observed.