Sinus delivery of sustained release therapeutics

Abstract

The invention provides biodegradable implants for treating sinusitis. The biodegradable implants have a size, shape, density, viscosity, and/or mucoadhesiveness that prevents them from being substantially cleared by the mucociliary lining of the sinuses during the intended treatment period. The biodegradable implants include a sustained release therapeutic, e.g., an antibiotic, a steroidal anti-inflammatory agent, or both. The biodegradable implants may take various forms, such as rods, pellets, beads, strips, or microparticles, and may be delivered into a sinus in various pharmaceutically acceptable carriers.

1 . A system comprising:
 a conduit for providing access to a paranasal sinus cavity and an implant for treating sinusitis,   wherein the implant comprises a therapeutic agent dispersed within a biodegradable polymer,   wherein the implant is sized and configured to be at least partially placed within the conduit and is sized and configured to be delivered from the conduit to a paranasal sinus cavity, and the implant having a first solid form while in the conduit and a second solid form in a paranasal sinus cavity, and   wherein the second form has at least one characteristic that substantially prevents clearance of the implant from the paranasal sinus cavity.   
     
     
         2 . The system of  claim 1  wherein the at least one characteristic is size of the implant. 
     
     
         3 . The system of  claim 1  wherein the at least one characteristic is shape of the implant. 
     
     
         4 . The system of  claim 1  wherein the at least one characteristic is density of the implant. 
     
     
         5 . The system of  claim 1  wherein the at least one characteristic is viscosity of the implant. 
     
     
         6 . The system of  claim 1  wherein the at least one characteristic is mucoadhesiveness of the implant. 
     
     
         7 . The system of  claim 1  wherein the therapeutic agent is selected from the group consisting of anti-infective agents, anti-inflammatory agents, and combinations thereof. 
     
     
         8 . The system of  claim 1  wherein the therapeutic agent comprises an anti-infective agent. 
     
     
         9 . The system of  claim 8  wherein the anti-infective agent is selected from the group consisting of antibacterial agents, antifungal agents, antiviral agents, and antiseptics. 
     
     
         10 . The system of  claim 8  wherein the anti-infective agent comprises an antibacterial agent. 
     
     
         11 . The system of  claim 10  wherein the antibacterial agent is selected from the group consisting of aminoglycosides, amphenicols, ansamycins, β-lactams, lincosamides, macrolides, nitrofurans, quinolones, sulfonamides, sulfones, tetracyclines, and any of their derivatives. 
     
     
         12 . The system of  claim 10  wherein the antibacterial agent comprises a β-lactam. 
     
     
         13 . The system of  claim 12  wherein the β-lactam comprises a penicillin. 
     
     
         14 . The system of  claim 13  wherein the penicillin comprises amoxicillin. 
     
     
         15 . The system of  claim 1  wherein the therapeutic agent is an anti-inflammatory agent. 
     
     
         16 . The system of  claim 1  wherein the therapeutic agent comprises a steroidal anti-inflammatory agent. 
     
     
         17 . The system of  claim 16  wherein the steroidal anti-inflammatory agent is selected from the group consisting of 21-acetoxypregnenolone, alclometasone, algestone, amcinonide, beclomethasone, betamethasone, budesonide, chloroprednisone, clobetasol, clobetasone, clocortolone, cloprednol, corticosterone, cortisone, cortivazol, deflazacort, desonide, desoximetasone, dexamethasone, diflorasone, diflucortolone, difluprednate, enoxolone, fluazacort, flucloronide, flumethasone, flunisolide, fluocinolone acetonide, fluocinonide, fluocortin butyl, fluocortolone, fluorometholone, fluperolone acetate, fluprednidene acetate, fluprednisolone, flurandrenolide, fluticasone propionate, formocortal, halcinonide, halobetasol propionate, halometasone, halopredone acetate, hydrocortamate, hydrocortisone, loteprednol etabonate, mazipredone, medrysone, meprednisone, methylprednisolone, mometasone furoate, paramethasone, prednicarbate, prednisolone, prednisolone 25-diethylamino-acetate, prednisolone sodium phosphate, prednisone, prednival, prednylidene, rimexolone, tixocortol, triamcinolone, triamcinolone acetonide, triamcinolone benetonide, triamcinolone hexacetonide, and any of their derivatives. 
     
     
         18 . The system of  claim 17  wherein the steroidal anti-inflammatory agent comprises budesonide. 
     
     
         19 . The system of  claim 17  wherein the steroidal anti-inflammatory agent comprises mometasone furoate. 
     
     
         20 . The system of  claim 17  wherein the steroidal anti-inflammatory agent comprises beclomethasone. 
     
     
         21 . The system of  claim 1  wherein the biodegradable polymer is a biodegradable polymer matrix. 
     
     
         22 . The system of  claim 1  wherein the biodegradable polymer comprises a mucoadhesive polymer. 
     
     
         23 . The system of  claim 1  wherein the biodegradable polymer comprises poly(lactic-co-glycolic)acid (PLGA) copolymer. 
     
     
         24 . The system of  claim 23  wherein the therapeutic agent comprises budesonide. 
     
     
         25 . The system of  claim 23  wherein the therapeutic agent comprises mometasone furoate. 
     
     
         26 . The system of  claim 1 , wherein the conduit comprises a distal portion and a proximal portion, and wherein the distal portion of the conduit is angulated from about 0° to about 175°. 
     
     
         27 . The system of  claim 1 , wherein the conduit comprises a pusher located within a lumen. 
     
     
         28 . The system of  claim 1 , wherein the conduit comprises a distal portion and a proximal portion, and wherein the distal portion of the conduit is stiffer than the proximal portion of the conduit.