Adhesive complex coacervates and methods of making and using thereof
Described herein is the synthesis of adhesive complex coacervates and their use thereof. The adhesive complex coacervates are composed of a mixture of one or more polycations and one or more polyanions. The polycations and polyanions in the adhesive complex coacervate are crosslinked with one another by covalent bonds upon curing. The adhesive complex coacervates have several desirable features when compared to conventional bioadhesives, which are effective in water-based applications. The adhesive complex coacervates described herein exhibit good interfacial tension in water when applied to a substrate (i.e., they spread over the interface rather than being beaded up). Additionally, the ability of the complex coacervate to crosslink intermolecularly increases the cohesive strength of the adhesive complex coacervate. The adhesive complex coacervates have numerous biological applications as bioadhesives and drug delivery devices. In particular, the adhesive complex coacervates described herein are particularly useful in underwater applications and situations where water is present such as, for example, physiological conditions.
1. A biodegradable adhesive complex coacervate comprising at least one biodegradable polycation polyamine and at least one polyanion, wherein the at least one biodegradable polycation polyamine comprises modified gelatin, wherein the modified gelatin is modified with one or more alkylamino groups, heteroaryl groups, or an aromatic group substituted with one or more amino groups and wherein the biodegradable polyamine polycation or polyanion is a synthetic compound, and the polycation and polyanion cross-link with each other to produce said adhesive.
2. The coacervate of claim 1 , wherein the biodegradable polyamine comprises gelatin modified with ethylenediamine.
3. The coacervate of claim 1 , wherein the polyanion comprises a polyphosphate compound.
4. The coacervate of claim 3 , wherein the polyphosphate compound comprises a natural compound or a synthetic analogue.
5. The coacervate of claim 1 , wherein the polyanion comprises a polyacrylate comprising one or more pendant phosphate groups.
6. The coacervate of claim 1 , wherein the polyanion comprises a polymer comprising at least one fragment comprising the formula II
wherein R 4 is hydrogen or an alkyl group, and n is from 1 to 10, or the pharmaceutically-acceptable salt thereof.
7. The coacervate of claim 1 , wherein the polyanion comprises at least one dihydroxyl aromatic group capable of undergoing oxidation, wherein the dihydroxyl aromatic group is covalently attached to the polyanion.
8. The coacervate of claim 1 , wherein the coacervate comprises at least one multivalent cation, and the multivalent cation comprises Ca +2 and/or Mg +2 .
9. The coacervate of claim 1 , wherein the coacervate further comprises one or more bioactive agents encapsulated in the complex.
10. The coacervate of claim 1 , wherein the coacervate further comprises a stabilized oxidant complex.
11. An adhesive complex coacervate comprising at least one polycation polyamine, at least one polyanion, and at least one multivalent cation, wherein the at least one biodegradable polycation polyamine comprises modified gelatin, wherein the modified gelatin is modified with one or more alkylamino groups, heteroaryl groups, or an aromatic group substituted with one or more amino groups and the polycation polyamine and polyanion actinically cross-link with each other to produce said adhesive.
12. The coacervate of claim 10 , wherein the polycation and polyanion comprises at least one fragment comprising the formula VII
wherein R 1 , R 2 , and R 3 are, independently, hydrogen or an alkyl group, X is oxygen or NR 5 , where R 5 is hydrogen or an alkyl group, and m is from 1 to 10, or the pharmaceutically-acceptable salt thereof, wherein at least one of R 2 or R 3 is an actinically crosslinkable group.
13. An adhesive produced by the process comprising:
(a) heating an adhesive complex coacervate comprising at least one polycation polyamine and at least one polyanion, wherein the polycation polyamine comprises modified gelatin, wherein the modified gelatin is modified with one or more alkylamino groups, heteroaryl groups, or an aromatic group substituted with one or more amino groups, wherein the polycation and polyanion crosslinks, wherein upon heating the adhesive complex coacervate the coacervate is converted to an insoluble solid; and
(b) crosslinking the polycation and polyanion in the insoluble solid to produce the adhesive.
14. An adhesive produced by the process comprising
(a) preparing an adhesive complex coacervate comprising admixing at least one polycation polyamine and at least one polyanion, wherein the polycation polyamine comprises modified gelatin, wherein the modified gelatin is modified with one or more alkylamino groups, heteroaryl groups, or an aromatic group substituted with one or more amino groups, and wherein at least one polycation or polyanion is a synthetic compound, and the polycation and polyanion crosslinks with each other;
(b) adjusting the pH of the adhesive complex coacervate to produce an insoluble solid; and
(c) crosslinking the polycation and polyanion in the insoluble solid to produce the adhesive.