Bioadhesion measurement

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. 

According to Duchene et al. [17], when tensiometry is used to measure the maximum detachment force as a function of the displacement of the upper support (function of the joint elongation), the work of bioadhesion can be defined as in Eq. (7). 

When a low extension rate is used for the measurements (for instance 1 mm/min), fVi can be considered as negligible and the fracture energy for zero extension rate (eo) is then equal to the reversible work of bioadhesion as shown by Eq. (10). 

Hertzog, B.A., and Mathiowitz, E., Novel Magnetic Technique to Measure Bioadhesion. In Bioadhesive Drug Delivery Systems (E. Mathiowitz, D.E. Chickering, III, and C.-M. Lehr, eds.), Marcel Dekker, Inc., New York, 1999, pp. 147-173. 

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. 

Measurement of tensile or shear stress is the most commonly used in vitro method to determine bioadhesion. All in vitro measurements provide a rank order of bioadhesive strength for a series of candidate polymers. Measurement of tensile strength involves quantitating the force required to break the adhesive bond between the test polymer... 

In vivo methods, which are few, measure the residence time of bioadhesives at the application site [47]. Techniques like y-scintigraphy, the perfused intestinal loop and radiolabeled transit studies using Cr-labeled bioadhesive polymer [48] and Tc-labeled polycarbophil [49] have been employed for this purpose. 

A confirmation of the soundness of electronic theory was derived from a recent study, performed by Bogotaj et al. [46], They measured the zeta potential of different polymer dispersions and mucosal homogenates and found a correlation between such a parameter and the force necessary to detach a polymer dispersion from the biological substrate. The adsorption theory states that the bioadhesive bond is due to van der Waals interactions, hydrogen bonds, and other related weak interactions [44],... 

Various mechanical testing methods have been used to assess the bioadhesive properties of materials and formulations. Review of the literature reveals that the technique most commonly used is the tensile test [82,85]. This test provides the measure of the force needed to detach a layer of the tested material or formulation from a mucosal substrate as a function of the displacement occurring at the bioadhesive interface. Besides maximum force of detachment, another parameter provided by tensile test is the work of adhesion calculated as the area under the force versus displacement curve. Such a parameter gives more complete... 

Artificial membranes soaked in animal mucin dispersions or animal model mucosae are used as biological substrates. Another apparatus proposed for in vitro measurements of bioadhesive properties of liquid formulations (polymer solutions or pessaries upon melting) consists of a thermostated inclined plane over which a mucosal membrane or a mucin film is layered. This test measures, as a function of time, the amount of formulation that after contact with the biological substrate, drops on a microbalance placed under the inclined plane [86] (Figure 22.3). 

Vermani, K., S. Garg, and L.J.D. Zaneveld. 2002. Assemblies for in vitro measurement of bioadhesive strength and retention characteristics in simulated vaginal environment. Drug Dev Ind Pharm 28 1133. 

Mikos and Peppas described the flow channel to measure the bioadhesion of polymer microparticles on mucin gels. Later Lehr et al. ° used an in situ loop model in the rat for the investigation of mucoadhesive microspheres (Fig. 3). They concluded that this approach allowed the study of the transit of particles. Another technique to study the mucoadhesive properties of microspheres is the electrobalance method, as... 

Measurement of either tensile or shear stress is the most commonly used in vitro method to measure bioadhesion. All in vitro measurements provide a rank... 

Unfortunately, values of yd and yp for mucus and glycoproteins, the main components of the mucous layer, are not yet available, but from the fact that the best candidates for bioadhesion are hydroxyl- and carboxyl-containing polymers, one can infer that the polar component is the predominant factor. The experimental data relating cellulose derivatives (mostly by measuring bioadhesive force) generally only compare NaCMC to one or two nonionic derivatives and the former always proved to be superior to the latter, and equivalent to other carboxyl-containing polymers (see e.g. [85]). 

Two recent studies provide more data on cellulose derivatives. Ranga Rao and Buri [86] measured in situ the adhesiveness of glass beads (as a model) and aspirin crystals coated with the polymers to be tested on the rat stomach or jejunum mucosae. The percentage of particles retained on the tissue upon washing by dilute HC1 (for the stomach) or a phosphate buffer (for the jejunum) was considered to be an index of bioadhesion (Table 17). 

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