ABSTRACT
Characterization and tuning of the porosity of amorphous starch materials are important for many applications, including controlled release of encapsulated proteins. The porosities of these materials in dry and hydrated states can have different physicochemical origins and properties. Here, porosities of dry cross-linked starch microspheres and their hydration-induced transformations were characterized by small angle X-ray scattering, scanning electron and optical microscopies, thermogravimetric analysis, sorption calorimetry, nitrogen sorption, and helium-pycnometry. The analyses revealed that dry microspheres consist of porous cores with pore diameters below 100 nm and shells which appeared to be denser but contained wider pores (100-300 nm). The outer crust of the microspheres shell is non-porous, which restricts diffusion of nitrogen, water, and ethanol. Partial hydration triggered an irreversible collapse of dry porosity at 12 wt% water. Further hydration resulted in interfacial changes and promoted wet porosity, related to characteristic distances between polymer chains.
Subject(s)
Dehydration , Starch , Humans , Microspheres , Nitrogen , Porosity , Starch/chemistry , Water/chemistryABSTRACT
Paclitaxel is one of the most important anti-cancer agents introduced during the last 20 years. However, the use of paclitaxel is limited by undesirable side effects as well as the development of drug resistance. Here, we report a synthetic strategy towards spiro-bicyclo[2.2.2]octane derivatives, which includes double Michael addition and ring-closing metathesis as key synthetic steps. This strategy was used to synthesize a series of spiro-bicyclic compounds designed to be paclitaxel mimetics, which were evaluated in human breast-derived cell lines. One of these paclitaxel mimetics showed toxicity, although at higher concentrations than paclitaxel itself. In addition, two other spiro-bicyclic compounds, lacking the paclitaxel side chain, showed toxicity.
Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Breast/drug effects , Octanes/pharmacology , Paclitaxel/analogs & derivatives , Paclitaxel/pharmacology , Spiro Compounds/pharmacology , Antineoplastic Agents/adverse effects , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Breast/cytology , Breast Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Female , Humans , MCF-7 Cells , Molecular Conformation , Molecular Mimicry , Octanes/adverse effects , Octanes/chemical synthesis , Octanes/chemistry , Paclitaxel/adverse effects , Paclitaxel/chemical synthesis , Paclitaxel/chemistry , Spiro Compounds/adverse effects , Spiro Compounds/chemical synthesis , Spiro Compounds/chemistry , Structure-Activity RelationshipABSTRACT
The synthesis and bronchorelaxing effects of a series of novel tetrahydroisoquinoline amides are described. The compounds were evaluated for their ability to relax LTD4 contracted isolated human small airways ex-vivo. Several compounds demonstrated highly efficacious bronchorelaxing properties. Cinnamide 71 was selected for further studies and constitutes a promising candidate as a novel bronchorelaxing agent for the treatment of pulmonary disorders.