Self-assembled block copolymer biomaterials for oral delivery of protein therapeutics.

Protein therapeutics have guided a transformation in disease treatment for various clinical conditions. They have been successful in numerous applications, but administration of protein therapeutics has been limited to parenteral routes which can decrease patient compliance as they are invasive and painful. In recent years, the synergistic relationship of novel biomaterials with modern protein therapeutics has been crucial in the treatment of diseases that were once thought of as incurable. This has guided the development of a variety of alternative administration routes, but the oral delivery of therapeutics remains one of the most desirable due to its ease of administration. This review addresses important aspects of micellar structures prepared by self-assembled processes with applications for oral delivery. These two characteristics have not been placed together in previous literature within the field. Therefore, we describe the barriers for delivery of protein therapeutics, and we concentrate in the oral/transmucosal pathway where drug carriers must overcome several chemical, physical, and biological barriers to achieve a successful therapeutic effect. We critically discuss recent research on biomaterials systems for delivering such therapeutics with an emphasis on self-assembled synthetic block copolymers. Polymerization methods and nanoparticle preparation techniques are similarly analyzed as well as relevant work in this area. Based on our own and others' research, we analyze the use of block copolymers as therapeutic carriers and their promise in treating a variety of diseases, with emphasis on self-assembled micelles for the next generation of oral protein therapeutic systems.

Amphiphilic silicones to mitigate lens epithelial cell growth on intraocular lenses.

Silicone intraocular lenses (IOLs) that resist lens epithelial cell (LEC) growth would greatly improve patient outcomes. Herein, amphiphilic surface modifying additives (SMAs) were incorporated into an IOL-type diphenyl silicone to reduce LEC growth without compromising opto-mechanical properties. The SMAs were poly(ethylene oxide)-silane amphiphiles (PEO-SAs) [H-Si-ODMSm-block-PEO8-OCH3], comprised of a PEO segment and siloxane tether of varying lengths (m = 0, 13, and 30). These three SMAs were each blended into the addition cure diphenyl silicone at varying concentrations (5, 10, 15, 20, and 25 µmol g-1) wherein the wt% of PEO was maintained for all SMAs at a given molar concentration. The chemical crosslinking and subsequent retention of SMAs in modified silicones was confirmed. Key material properties were assessed following equilibration in both air and aqueous environments. Silicones modified with SMAs having longer tethers (m = 13 and 30) underwent rapid and substantial water-driven restructuring of PEO to the surface to form highly hydrophilic surfaces, especially as SMA concentration increased. The % transmittance was also maintained for silicones modified with these particular SMAs. The moduli of the modified silicones were largely unchanged by the SMA and remained in the typical range for silicone IOLs. When the three SMAs were introduced at the highest concentration, modified silicones remained non-cytotoxic and LEC count and associated alpha-smooth muscle actin (α-SMA) expression decreased with increasing tether length. These results demonstrate the potential of silicones modified with PEO-SA SMAs to produce LEC-resistant IOLs.