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 biodegradable implant for treating sinusitis comprising a sustained release therapeutic agent dispersed within a biodegradable matrix, wherein the biodegradable implant is sized and configured to be at least partially placed within a conduit and is sized and configured to be delivered from the conduit to a paranasal sinus cavity, and has a first solid form prior to delivery to a paranasal sinus cavity and a second solid form after delivery of the biodegradable implant to a paranasal sinus cavity from the conduit, and wherein the second form has at least one characteristic that substantially prevents clearance of the implant from a paranasal sinus cavity during a treatment period. 
     
     
         2 . The biodegradable implant of  claim 1  wherein the at least one characteristic is size of the implant. 
     
     
         3 . The biodegradable implant of  claim 1  wherein the at least one characteristic is shape of the implant. 
     
     
         4 . The biodegradable implant of  claim 1  wherein the at least one characteristic is density of the implant. 
     
     
         5 . The biodegradable implant of  claim 1  wherein the at least one characteristic is viscosity of the implant. 
     
     
         6 . The biodegradable implant of  claim 1  wherein the at least one characteristic is mucoadhesiveness of the implant. 
     
     
         7 . The biodegradable implant of  claim 1  wherein the sustained release therapeutic agent is selected from the group consisting of anti-infective agents, anti-inflammatory agents, and combinations thereof. 
     
     
         8 . The biodegradable implant of  claim 1  wherein the sustained released therapeutic agent comprises an anti-infective agent. 
     
     
         9 . The biodegradable implant 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 biodegradable implant of  claim 8  wherein the anti-infective agent comprises an antibacterial agent. 
     
     
         11 . The biodegradable implant 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 biodegradable implant of  claim 10  wherein the antibacterial agent comprises a β-lactam. 
     
     
         13 . The biodegradable implant of  claim 12  wherein the β-lactam comprises a penicillin. 
     
     
         14 . The biodegradable implant of  claim 13  wherein the penicillin comprises amoxicillin. 
     
     
         15 . The biodegradable implant of  claim 1  wherein the sustained release therapeutic agent is an anti-inflammatory agent. 
     
     
         16 . The biodegradable implant of  claim 1  wherein the sustained release therapeutic agent comprises a steroidal anti-inflammatory agent. 
     
     
         17 . The biodegradable implant 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 biodegradable implant of  claim 17  wherein the steroidal anti-inflammatory agent comprises budesonide. 
     
     
         19 . The biodegradable implant of  claim 17  wherein the steroidal anti-inflammatory agent comprises mometasone furoate. 
     
     
         20 . The biodegradable implant of  claim 17  wherein the steroidal anti-inflammatory agent comprises beclomethasone. 
     
     
         21 . The biodegradable implant of  claim 1  wherein the biodegradable matrix is a biodegradable polymer matrix. 
     
     
         22 . The biodegradable implant of  claim 1  wherein the biodegradable matrix comprises a mucoadhesive polymer. 
     
     
         23 . The biodegradable implant of  claim 1  wherein the biodegradable matrix comprises poly(lactic-co-glycolic)acid (PLGA) copolymer. 
     
     
         24 . The biodegradable implant of  claim 23  wherein the sustained release therapeutic agent comprises budesonide. 
     
     
         25 . The biodegradable implant of  claim 23  wherein the sustained release therapeutic agent comprises mometasone furoate.