Mechanism of Bioadhesion

The bioadhesion mechanism is not well defined. The Hterature indicates that bioadhesion takes place in three steps the deposition and attachment of a protein layer, followed by cell deposition. The important parameter corresponds to the formation of a water monolayer on the substrate (Fig. 12.1). 

Because of its low wettabihty (and high water contact angle), a substrate with a low surface energy could interact neither with biomolecules nor with water molecules. There is no alBnity, only electrostatic repulsion of the proteins. Hence, the organization of the biomolecules at the interface is not uniform, and cell aggregates are formed. 

---

Measurement of bioadhesion not only helps in screening the candidate polymer, but to study the mechanism of bioadhesion as well. However, performance of the final dosage form containing the polymer and the drug is the best test. 

Park, H. On the mechanism of bioadhesion. University of Wisconsin-Madison, 1986. 

The mechanisms of bioadhesion have been reviewed by Kaelble and Moacanin [62] and by Peppas and Buri [84] and may be classified as chemical (electronic and adsorption theories) and physical (wetting, interpenetration and fracture theories). 

Bioadhesion gels generally employ the same mechanism as involves ointments and the tapes to hold them in place. However, the adhesion mechanism of ointments is different from the adsorption mechanism of bioadhesion gels. In the cases of the skin, the interface between the... 

Matthew V. Tirrell (Co-Chair) is Dean of the College of Engineering at the University of California at Santa Barbara. He was previously Professor and Head of the Department of Chemical Engineering and Materials Science at the University of Minnesota, where he served as Director of its Biomedical Engineering Institute. He received a B.S. from Northwestern University and a Ph.D. from University of Massachusetts. His interests are in transport and interfacial properties of polymers, with particular emphasis on molecular-scale mechanical measurements, bioadhesion, and new materials development. He is a member of the National Academy of Engineering. 

Bioadhesion to the vaginal substrate implies knowledge and demonstration of the mechanism of interaction. In the present case, mucoadhesion, bioadhesion, and substantivity can be used interchangeably when evaluating the mucosa as a substrate. Several forces may be active, such as electrostatic, hydrophobic, and hydrogen bonding, giving rise to surface interactions between the polymer and the mucosal substrate or diffusion into the mucus layer [48,49]. 

Several biomucoadhesive dosage forms have been developed and the mechanism(s) of bioadhesion have been elucidated. 

Chickering, D.E., III, and E. Mathiowitz, eds. 1999. Definitions, mechanisms and theories of bioadhesion. In Bioadhesive drug delivery systems Fundamentals, novel approaches and development, 1. New York Marcel Dekker. 

The different theories that have been proposed to explain the bioadhesion phenomenon are hereafter summarized. The design of bioadhesive drug delivery systems should take into account the mechanisms on which the bioadhesion phenomenon is based. An insight into bioadhesion theories could help formulators to design bioadhesive drug delivery systems with optimal performances. 

Chickering, D. E., and Mathiowitz, E. Definitions, mechanisms, and theories of bioadhesion, in Bioadhesive Drug Delivery Systems Fundamentals, Novel Approaches, and Development, New York Marcel Dekker, 1999. 

The principal mechanism for bioadhesion of oral patches appears to be physical entanglement of the adhesive polymer of the patch in the mucus glycoprotein chains, with secondary (electrostatic, hydrogen, hydrophobic) chemical bonding playing a minor role. 

The hydrophilic groups on mucoadhesive polymers and the large amount of water associated with mucin present two possible adhesion mechanisms (i) hydrogen bonding and (ii) interpenetration of a swollen gel network with hydrated mucin. Many methods have been used for the assessment of bioadhesive properties, including fluorescent techniques and tensile tests. By using these methods, a number of natural and synthetic polymers have been discovered possessing mucoadhesive properties. 

Duchene, D. Ponchel, G. Principle and investigation of the bioadhesion mechanism of sohd dosage forms. Biomaterials 1991, 13, 709-714. 

Jones DS, Woolfson AD, Djokic J, Coulter WA. Development and mechanical characterization of bioadhesive semi-solid, polymeric systems containing tetracycline for the treatment of periodontal diseases. Pharm Res 1996 13(11) 1734—1738. 

Yamamoto et al. [4] showed that 0.01% aprotinin (a serine protease inhibitor) reduced the metabolism of insulin and proinsuHn in homogenates of albino rabbit buccal mucosa, which otherwise would have occurred at 70-80% within 2.5 hours. Moreover, Lehr et al. suggest that polycar-bophil, a bioadhesive polymer, may protect some peptides from proteolysis, though the mechanism of this is unknown [5]. Others [6] have developed a series of pro-dmgs for peptides, with the aim of overcoming the metabohc barrier imposed by different peptidases. Stable prodrugs proved to be N-hydroxymethylated derivatives of the assessed dipeptides Gly-L-Leu and Gly-L-Ala [6]. 

Surface active agents with bioadhesive microspheres or nanospheres have been discussed in the previous section. As these systems are suited to the appHcation on mucosal membranes, they are also used in peroral formulations. Furthermore, the formulation of proteins together with so-called carriers has been developed during the past few years. These carriers range from N-acylated a-amino acids [136] to aromatic amides and sulfamides [137] the mechanism of the latter system remains the subject of investigation. Carriers do... 

---