Science and Technology of Bioadhesive-Based Targeted Oral Delivery Systems

Novel hydrophobic bioadhesive polymers and dosage designs are now available to effectively achieve tailored release kinetics of a broad range of drugs to meet the clinical needs.
Nov 02, 2008

The use of bioadhesive polymers as a means of delivering therapeutic agents to the gastrointestinal tract (GIT) has been a focus of attention during the past two decades (1, 2). Bioadhesive oral drug delivery systems exploit the interaction between the mucus and bioadhesive polymers and thus offer significant advantages (3, 4) (see sidebar). Oral delivery systems formulated with bioadhesive polymers may increase GIT residence time, thereby improving oral bioavailability as the formulation achieves greater opportunity to interact closely with the absorption site (5, 6). Bioadhesive polymeric systems may also be useful for coating damaged esophageal and intestinal wall tissues, thus providing defense against various irritants (7). The ability to maintain an oral delivery system at the target location for an extended period of time has great appeal for the treatment of both local conditions and sustained systemic absorption (8–10).

Despite significant research on bioadhesive polymers, the phenomenon of bioadhesion is not yet fully understood. Adhesion of bioadhesive polymers to mucus is a complex interaction and is regulated to a great extent by the intrinsic properties of the polymer, the biological substrate, and the surrounding environment (11). The term bioadhesion is defined as adhesion to a biological surface (i.e., mucus and/or mucosal surface). Instances in which the polymeric system interacts with the mucus coating only are referred to as mucoadhesion (12). To develop an ideal oral bioadhesive system, one must have a thorough understanding of mucosa, bioadhesive polymers, and mucous-polymer interactions in the physiological environment.

Major attributes of oral bioadhesive based systems (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
GI mucosa is composed of high molecular weight glycoproteins that are hydrated with a continuous adherent blanket of mucin. Mucin glycoproteins are rich with fucose and sialic acid groups at the terminal ends that provide a net negative charge in the acidic environment. The thickness of the mucin gel layer varies in various regions of the GIT, with thickness ranging between 50 and 500 μm in the stomach to 15–150 μm in the colon. The thickness of the mucus gel that covers the GI epithelium is attributed to the steady state between the mucus secretions and its erosion via enzymatic and mechanical degradation. Cohesion of the mucin gel depends on the glycoprotein concentration.

The mucus layer is created biologically to protect the underlying tissues from diffusing or corrosive elements such as enzymes, acids, and other toxic molecules. As a viscoelastic gel, it helps in the transport of food over the epithelium, thereby minimizing potential erosive damage. The mucus layer, in addition to providing protection, imparts a barrier to drug absorption. The following mucin–polymer interactions have been proposed:
  • Wetting and swelling of the polymer to permit intimate contact with the biological tissue
  • Interpenetration of bioadhesive polymer chains and entanglement of polymer and mucin chains
  • Formation of weak chemical bonds
  • Sufficient mobility to allow spreading
  • Water transport followed by mucosal dehydration.

Figure 1: Schematic representation of interactions between bioadhesive and mucus polymer chains. (ALL FIGURES AND TABLES ARE COURTESY OF THE AUTHOR.)
As the bioadhesive delivery system comes into contact with the mucus layer, various nonspecific (van der Waals, hydrogen bonding, and hydrophobic interactions) or specific interactions occur between the complimentary structures (see Figure 1). However, these interactions are of limited duration because of the turnover process of mucin. Although this phenomenon is favorable from the toxicological perspective of keeping unwanted materials from gaining access to the body, it is not optimal for maintaining the bioadhesive delivery system at the mucosal surface. Hence, for a bioadhesive delivery system to be successful, it should release drug contents during the limited adhesion time (13).