Echolucent implant compositions and methods
Implantable materials visible under ultrasound may be delivered to a selected placement site and biodegrade after a certain period of time. Ultrasound visible implantable materials may be delivered through an applicator and may include ultrasound contrast agents and/or radiopaque agents. Applications include monitoring the delivery of an implant of the implantable materials to the placement site with ultrasound and delivery of therapeutic agents to a tissue at the placement site for treating a patient.
1. A pharmaceutically acceptable implant composition comprising: a hydrogel precursor composition, a therapeutic agent, and a pharmaceutically acceptable fluid, wherein the hydrogel precursor composition comprises a first precursor compound with a plurality of first functional groups and a second precursor compound with a plurality of second functional groups, wherein the first functional groups are capable of forming covalent bonds with the second functional groups at physiological conditions, and wherein the pharmaceutically acceptable implant composition is visible under ultrasound following reaction of the hydrogel precursor composition to form a covalently-cross-linked, hydrolytically biodegradable hydrogel.
2. The pharmaceutically acceptable implant composition of claim 1 further comprising a radiopaque agent.
3. The pharmaceutically acceptable implant composition of claim 2 wherein the radiopaque agent is covalently attached to the hydrogel precursor composition.
4. The pharmaceutically acceptable implant composition of claim 1 wherein the hydrogel comprises hydrogel particles having an average diameter from about 10 microns to about 500 microns.
5. The pharmaceutically acceptable implant composition of claim 1 wherein the hydrogel comprises hydrogel particles having an average diameter from about 125 microns to about 500 microns.
6. The pharmaceutically acceptable implant composition of claim 1 comprising an ultrasound contrast agent.
7. The pharmaceutically acceptable implant composition of claim 1 wherein the therapeutic agent comprises an anesthetic, a steroid, a chemotherapeutic agent, or combinations thereof.
8. The pharmaceutically acceptable implant composition of claim 1 wherein a volume of the pharmaceutically acceptable implant composition increases no more than 50% in an in vitro physiological saline solution or an in vivo environment in a tissue.
9. The pharmaceutically acceptable implant composition of claim 1 wherein the hydrogel has a time for complete degradation from about 7 days to about 180 days in an in vivo environment in a tissue.
10. The pharmaceutically acceptable implant composition of claim 1 wherein the hydrogel is hydrolytically biodegradable in vivo to produce degradation products that are absorbed into the circulatory system and cleared from the body via renal filtration.
11. The pharmaceutically acceptable implant composition of claim 1 wherein the degradation products of the hydrogel comprise a polyethylene glycol covalently bound to a radiopaque agent, wherein the radiopaque agent comprises iodine.
12. The pharmaceutically acceptable implant composition of claim 1 wherein the pharmaceutically acceptable implant composition comprises a slurry or liquid that is deliverable through an applicator.
13. The pharmaceutically acceptable implant composition of claim 1 further comprising an osmotic agent wherein the osmotic agent comprises a linear hydrophilic polymer.
14. The pharmaceutically acceptable implant composition of claim 13 wherein the osmotic agent comprises polyethylene glycol, a polyethylene glycol-containing precursor, or combinations thereof.
15. The pharmaceutically acceptable implant composition of claim 1 wherein the pharmaceutically acceptable implant composition is deliverable to a tissue at a placement site through an applicator, and wherein the applicator comprises a syringe, a catheter, a needle, a cannula, a hollow wire, a double barreled container, or combinations thereof.
16. The pharmaceutically acceptable implant composition of claim 15 wherein the pharmaceutically acceptable implant composition is adherent to the tissue.
17. The pharmaceutically acceptable implant composition of claim 1 wherein the first or the second precursor compound comprises a polyethylene glycol.
18. The pharmaceutically acceptable implant composition of claim 1 wherein the first or the second precursor compound comprises a branched polyethylene glycol having a plurality of arms.
19. The pharmaceutically acceptable implant composition of claim 1 wherein the hydrogel and/or the pharmaceutically acceptable fluid comprise the therapeutic agent.
20. The pharmaceutically acceptable implant composition of claim 1 wherein the therapeutic agent further comprises a surfactant, a lipid, a polyethylene glycol, a distinct release rate modifying agent, or a combination thereof.
21. The pharmaceutically acceptable implant composition of claim 1 wherein the therapeutic agent comprises particulates.
22. The pharmaceutically acceptable implant composition of claim 1 comprising gas microbubbles, microparticles comprising the therapeutic agent, hydrophobic microdomains, hydrogel particles, micelles, a suspension of the first precursor compound, a suspension of the second precursor compound, and/or microparticulates of the therapeutic agent.
23. A method for the delivery of the pharmaceutically acceptable implant composition of claim 1 , the method comprising placing the pharmaceutically acceptable implant composition at a placement site between a first tissue location and a second tissue location using an applicator.
24. A method for the delivery of the pharmaceutically acceptable implant composition of claim 1 , the method comprising placing the pharmaceutically acceptable implant composition at a placement site, wherein the placement site is a muscle tissue location and/or a nerve tissue location, and wherein the applicator comprises a syringe, a catheter, a needle, a cannula, a hollow wire, a double barreled container, or combinations thereof.