Novel Carriers for Oral Delivery of Hydrophobic Drugs

Abstract

For the first time, the glucose-6-acrylate-1,2,3,4-tetraacetate (GATA) monomer was prepared under mild conditions. The removal of protecting acetate groups from GATA was carried out before the silylation and then Me 3 Si was covalently linked with glucose acrylate (GA). Cubane-1,4-dicarboxylic acid (CDA) was covalently linked with 2-hydroxyethyl methacrylate (HEMA). The silyl-linked GA is abbreviated as TMSiGA. CDA linked to two HEMA groups was used as the cross-linking agent (CA). Free radical crosslinking co-polymerization of the methacrylic acid (MAA) and hydrophobic glycomonomer (TMSiGA) with two different molar ratios of CA was carried out at 60-70 • C. The compositions of the cross-linked threedimensional polymers were determined by FT-IR spectroscopy. A model hydrophobic drug, the steroid hormone estradiol, was entrapped in these gels and the in vitro release profiles were carried out in enzymefree simulated gastric and intestinal fluids (SGF and SIF, respectively). To overcome the hydrophobicity of estradiol, the buffers for estradiol were modified by adding ethanol. The influence of the structures and amounts of silane monomers on the swelling and drug-release behaviors were studied.

Pilot-Scale Production of Dimethyl 1,4-Cubanedicarboxylate

“…Cubane ( 1 ) was the first of two of the Platonic solids to succumb to chemical synthesis, the other being dodecahedrane . Since its systematic synthesis by Eaton and Cole in 1964, many of its derivatives have been prepared and investigated for a myriad of purposes, including as pharmaceuticals, − drug delivery vectors, − liquid crystals, , polymeric materials, − explosives, and fuels. − The most convenient synthetic access to the cubane ring system is through its 1,4-dicarboxylates, namely 1,4-cubanedicarboxylic acid ( 2 ) and dimethyl 1,4-cubanedicarboxylate ( 3 ). The work reported herein builds on previous synthetic work from this and other laboratories, and provides a reliable process that can be used to prepare kilogram quantities of the synthetically versatile dimethyl 1,4-cubanedicarboxylate ( 3 ).…”

Synthesis and Characterization of Novel Polymers Containing Pendant Silyl Ether Groups

“…In the preparation of polymerzable silyl monomers it is necessary to create synthetic conditions mild enough to allow attachment with no adverse effect on the 4-HVB. This monomer was prepared by using organosilyl chloride in the presence of imidazole with 4-HBA at room temperature [8]. The FT-IR spectrum shows the complete O-deacetylation.…”

“…Attaching the organosilyl groups to macromolecular chains should lead to important modifications of polymer properties, such as gas permeability and permselectivity parameters, mechanical, thermal and surface properties, as well as photochemical reactivity [3][4][5][6]. On the other hand, silicones, or silicon polymers, have a number of advantages for use in medical devices and drug-delivery systems [7,8]. These polymers usually show high oxygen permeability and a reasonably high permselectivity of oxygen against nitrogen.…”

Cubanes in Medicinal Chemistry

“… Compound 66 has also been developed as a polymerization precursor. Subjecting 66 to free radical copolymerization with various drugs leads to novel and targeted delivery systems. − Nitroxyalkyl groups substituted onto cubane with various linkers have been developed and explored for their anti-ischemic activity (compounds 67 ) . Compound 67a showed an improved ratio between the necrotic and ischemic zones (36.1%) when compared to the lead compound nicorandil ( 68 , 42.0%), where a mononitroxyalkyl is substituted on a pyridine.…”