Lightly crosslinked poly(ethylene glycol)-tethered, pH-responsive biomaterials
Significant effort has been spent on altering the pharmacokinetic profile of drugs and identifying ways to slow down the GI transit of the therapeutic, especially that of the small intestine, the location where the majority of absorption occurs. The two main areas of thrust for research pertaining to increasing the bioavailability of drugs possessing narrow absorption windows are retaining the dosage form in the stomach (gastroretentive) and slowing down transit time in the small intestine (mucoadhesive). Gastroretentive dosage forms maintain the drug delivery system above the absorption window and release the drug accordingly. Mucoadhesion affords the ability to slow upper GI transit by maintaining the dosage form at the site of absorption through some type of interaction with the intestinal mucosa. The motility of the gastrointestinal tract plays a major role in appropriately engineering a dosage form. The delivery system must be designed so that it works with the digestive system to accomplish the goal of targeting the area where the narrow absorption window of the therapeutic exists and controlling the release to enhance the pharmacokinetic profile. Smart biomaterials composed of pH responsive polymers, poly((meth)acrylic acid), were synthesized using a precipitation polymerization technique. The microparticles were grafted with linear polymer chains (PEG) that are capable of complexing with the hydroxyl groups of the polyacid and interpenetrating into the mucus gel layer upon entry into the small intestine. Upon introduction of an alkaline solution, these materials imbibe a significant amount of water and create a highly viscous solution. The gelled materials serve as both a controlled release membrane and resist the inertial forces associated with motility, thereby effectively slowing down the transit of the dosage form. The amount and length of the linear chain were varied to investigate their effects on the release behavior of a model compound.