(51d) A Self-Folding Hydrogel Device for Oral Drug Delivery

Mucoadhesive drug delivery systems (MDDSs) have attracted considerable interest because of their sustained drug release profile at the absorption site and increased drug bioavailability due to the intimate contact with the absorbing tissue. MDDSs typically present in the form of symmetric micro- and nano-spheres or asymmetric patches. The mucoadhesion occurs through surface-surface contact. As a result, the residence time of MDDS on mucus is limited due to the continuous shedding of surface mucus. In this study, self-folding miniature devices are proposed to develop based on the selected integration of a number of micro-manufacturing modules such as soft-lithography and micro-imprinting. The key part of the device is a finger-like bilayered structure. One is a pH-sensitive hydrogel based on crosslinked poly(methyacrylic acid) (PMAA) that swells significantly when in contact with the body fluid, while the other is a non-swelling layer based on poly(hydroxyethyl methacrylate) (HEMA). The differential swelling causes the bilayer to fold in biological fluids. A mucoadhesive drug layer entrapped biocompatible cationic liposomes is attached on the bilayered structure. To evaluate the device functionalities, mucoadhesion measurement and targeted unidirectional release are being conducted for trans-luminal delivery of two model drugs, acid orange 8 and bovine insulin. Additionally, a closed loop animal model is employed to determine the insulin bioavailability. It is expected that the self-folding device first attaches to the mucosal surface and then curls into the mucus, leading to enhanced mucoadhesion in the mode of ?grabbing?. Furthermore, the non-swelling poly(HEMA) layer can serve as a diffusion barrier, minimizing any drug leakage in the small intestine. Due to the localized high drug concentration and the permeation enhancement of biocompatible lipid-based nanoparticles, the self-folding device exhibited an improved transport for hydrophilic macromolecules across the mucosal epithelium. This novel delivery device will be of great benefit to the advancement of oral administration of peptide and protein drugs. Since the mucus layer covers many tissues at other specific sites, the device may be applied for ocular, buccal, vaginal and rectal administrations. The polymer self-folding phenomena at the microscale can also be applied as probe arrays for bio/chemical sensing, carriers in cell-based bioreactors, and tissue clamping.