Лако-красочные материалы — производство

The physicochemical criteria for potential bioadhesion have been studied extensively for both natural and synthetic polymers. Past studies have shown that polyethylene glycols [16], sodium carboxymethyl cellulose [17], and potassium carrageenan [16] need a mini­mum molecular weight for bioadhesion. Further, the molecular weight of a compound has been shown to be proportional to its bioadhesive strength. For most polymers, increasing the molecular weight means an increase in length of the molecule, which can have an effect on the physical penetration and subsequent entanglement of the polymer with the sub­strate. Interpenetration and entanglement of an adhesive polymer with a mucin substrate is partly responsible for its bioadhesive strength [17], and any parameter that alters this process will have an effect on bioadhesive-mucin interaction.

The chains of water-insoluble swellable polymers are connected to cross-linking agents. As the amount of cross-linking is increased, the diffusion coefficient of the polymer chains is decreased with a subsequent decrease in interdiffusion between the polymer and substrate and a decrease in the polymer’s bioadhesive properties [18,19]. This increase in cross-linking also lowers chain-segment mobility and flexibility, which can reduce the

amount of interpenetration and entanglement of the polymer with its substrate. It has been suggested that there is an optimal chain mobility because too little or too much flexibility of the side chains can lead to a decrease in interpenetration with the mucus [20].

The interactions between bioadhesives and their substrates occur through covalent bonds, electrostatic interactions, and hydrogen-bond formation. Due to the potential toxi­city involved in covalent bonding of an adhesive to a biological substrate (e. g., cyanoacry­late “superglue’’), polymers that adhere via electrostatic interactions and hydrogen bonding are preferred. Anionic, cationic, and neutral polymers have been studied exten­sively for their bioadhesive properties [21-23]. When the bioadhesive strength of the hydro­colloids, acrylic acid and 2-hydroxyethyl methacrylate (containing carboxyl groups and neutral groups, respectively) were measured, the role of the negatively charged groups was clearly established [23]. It was also determined that both the charge sign and density are important [21,24]. When both toxicity and bioadhesive properties are considered, polya­nionic polymers appear to be better bioadhesives than polycations. Also, polyanions with carboxyl groups appear to be better than those with sulfate groups when only toxicity is considered. Thus the pH of the media can play a significant role in a polymer’s bioadhesive strength, depending on the pKa of the adhesive. Since, as mentioned above, the mucus layer and the mucosal epithelium both carry a net negative charge, electrostatic interactions are likely to occur with polyanionic molecules leading to increased bioadhesion.

Many polymers show significant bioadhesive strength when they are not ionized. Bioadhesive polymers often have numerous hydrophilic functional groups such as car­boxyl, hydroxyl, amide, and sulfate groups which can form hydrogen bonds with the biological substrates [16]. These bonds may play a larger role in bioadhesion than the electrostatic interactions mentioned above. Studies using cross-linked polyacrylic acid (pKa = 4.75) show that the adhesion is greatest when the carboxylate groups are in the free acid form and show a significant drop in adhesive strength above pH 4.0 [18], thus illustrating that hydrogen bonding is the dominant mechanism.

Sufficient hydration of a polymer is also of importance in bioadhesion. As bioadhe­sives hydrate in aqueous media, they swell and form gels with fixed charged groups inside the network. These fixed charged groups result in the development of a swelling force or a net osmotic pressure which drives the surrounding solvent from the more dilute external bulk solution into the polymer network [25]. It was found that the degree of hydration decreases as the number of charged acrylic acid groups decreases or the amount of uncharged groups on methyl methacrylate increases [26]. Thus the rate and extent of water uptake by a polymer is dependent on the type and number of hydrophilic functional groups present in the polymer and also on the ionic strength and pH of the surrounding media.

The degree of hydration of a polymer is pertinent to its adhesive properties because sufficient water is needed to properly hydrate and expand the adhesive. If insufficient amounts of solvent are available or hydration is slow, the polymer is not fully hydrated and this limits the flexibility and mobility of the polymer chains, which is crucial to their diffusion and penetration into a substrate.

Pores in the hydrated polymer are formed due to chain flexibility and chain move­ment [27] and are a characteristic of the expanded nature of the polymer network. Formation of pores is lowered with decreased hydration and this limits the active adhesive sites available on the polymer network. As the degree of hydration increases with an increase in the density of charged groups [26], so does the mesh size of the network. Indeed, it was determined that the tensile strength of a mucoadhesive is directly propor­tional to the mesh size of the polymer network [28]. Thus as with mucin, the expanded nature of the network of an adhesive is an important factor in controlling adhesive strength.

If a drug delivery system using bioadhesives is placed in an aqueous medium, the polymer will absorb water. This absorption of water leads to the formation of aqueous channels and subsequent desorption of water-soluble drug [29-31] (i. e., the hydration of the polymer allows the polymer chains to extend and form aqueous pores in the polymer matrices and allows diffusion of drug molecules out of the polymer matrix to the underlying absorbing epithelium). Controlling the swelling rate [32], the cross-linking density of the polymer network [33], ionicity and pH of the media [33,34], solubility of the active drug, and so on, of a drug delivery system containing a bioadhesive can all be manipulated to optimize release of the drug from the delivery system to the targeted membrane.