Superior Adhesion of a Multifunctional Protein‐Based Micropatch to Intestinal Tissue by Harnessing the Hydrophobic Effect

Abstract

Drug delivery systems comprising drug carriers capable of adhering to intestinal tissue have considerable potential to realize more sophisticated systemic drug delivery and topical drug treatments in the intestinal tract. The development of innovative strategies for improving the adhesion efficiency of carriers is of high importance for the advancement of this field. Herein, a novel approach to achieving high adhesion efficiency of drug carriers is presented, where the accessibility of the carrier to the intestinal surface and its subsequent adhesion to the intestinal tissue are promoted by utilizing the thermodynamic tendency of the hydrophobic carrier and its dispersion solvent, triacetin, to be excluded from the aqueous environment. Drug carriers are fabricated using proteins, imparting multiple functions, including drug release and the removal of reactive oxygen species (ROS). Results of ex vivo studies indicate that this multifunctional protein‐based carrier, “protein micropatch,” adheres to various mouse intestinal tissues, including the small intestine, colon, and inflamed colon, with high efficiency. Furthermore, protein micropatches, administered to mice via oral or rectal routes, successfully adhere to the intestinal tract. This approach and the highly functionalized carrier described in the study have the potential to significantly contribute to the development of bioadhesive carrier‐based drug delivery systems.

Multifunctional Micromachines Constructed by Combining Multiple Protein-Based Components with Different Functions

“…Cross-linking of protein was conducted according to a method developed in previous studies. , A 450 μM bovine serum albumin (Sigma, MO, USA) solution, a mixture solution of 450 μM albumin and 4.5 μM bovine liver catalase (11,000 U/mg; Wako, Tokyo, Japan), or a mixture solution of 450 μM albumin and 4.5 μM HRP (200 U/mg, Wako) was prepared in PBS (pH = 7.4). Then, these protein solutions were reacted with 215 mM ethylene glycol diglycidyl ether (EGDE; Wako) with vigorous stirring for 24 h at 25 °C.…”

“…The cross-linked protein solution was utilized because, when a machine was prepared from a water-soluble native protein, it easily dissolved in water. The cross-linking of the protein was achieved using the method optimized in my previous studies, in which proteins reacted with a cross-linker having epoxy groups at the lowest concentration necessary to prepare a water-insoluble proteinaceous construct to avoid excess cross-linking that leads to the disruption of the structural and functional characteristics of the native protein. − …”

Blue-ringed octopus-inspired microneedle patch for robust tissue surface adhesion and active injection drug delivery

“…Making the drug delivery system stable on the tissue surface is also crucial ( 9 , 37 , 38 ). The humid environment and mutual friction on the tissue surface pose a notable challenge to adhesion ( 10 , 39 , 40 ), similar to the grasping challenge faced by the blue-ringed octopus in seawater. The octopus suction cup structure for bonding reinforcement has been extensively studied, with satisfactory outcomes ( 14 ).…”

“…Moreover, the concentration control of drug release is also required when administering the drug in many situations, such as anti-inflammation, anti-angina, and antitumor, thus achieving rapid onset and long-term maintenance therapy (6)(7)(8). Now, although some delivery platforms have been developed to achieve controlled drug release into tissues with the ability of puncturing (1,5,9) or other superficial administration wet-adhesion platforms can bond on the surface of the tissue (2,10), few formulas could exhibit excellent properties to cover all the clinical needs for intratissue topical medication.…”