Drug-delivering composite structures

Abstract

Composite structures composed of a fibril core and a polymeric coat and designed capable of encapsulating both hydrophobic and hydrophilic bioactive agents while retaining the activity of these agents are disclosed. Further disclosed are processes of preparing such composite structures, and medical devices and disposable articles made therefrom.

1 - 13 . (canceled) 
     
     
         14 . A composite structure comprising a medical device and a polymeric porous coating encapsulating at least one bioactive agent, the composite structure comprising:
 (i) the medical device, wherein the medical device has a solid density and is non-degradable and wherein the medical device is a needle or a drug delivery port;   (ii) an interface between the medical device and the polymeric porous coating encapsulating the at least one bioactive agent; and   (iii) the polymeric porous coating encapsulating the at least one bioactive agent; wherein the interface exhibits strong adhesion between the medical device and the polymeric porous coating encapsulating the at least one bioactive agent, thereby providing tight contact between the medical device and the polymeric porous coating with no gaps; and wherein the polymeric porous coating
 (a) is a freeze dried solid polymer comprising the at least one bioactive agent encapsulated therein; and 
 (b) is configured to release the at least one bioactive agent at a predetermined release rate; 
   and   
       the at least one bioactive agent retains at least one biological activity. 
     
     
         15 . The composite structure  claim 14 , wherein the polymeric porous coating comprises at least one biodegradable polymer. 
     
     
         16 . The composite structure  claim 14 , wherein the polymeric porous coating comprises an aliphatic polyester. 
     
     
         17 . The composite structure  claim 16 , wherein the aliphatic polyester is poly(glycolic acid), poly(lactic acid), polydioxanone (PDS), poly(alkylene succinate), poly(hydroxybutyrate), poly(butylene diglycolate), or poly(epsilon-caprolactone), or any co-polymer, blend or mixture thereof. 
     
     
         18 . The composite structure  claim 17 , wherein the aliphatic polyester is poly(L-lactic acid), poly(glycolic acid) or poly(lactic-co-glycolic acid), or any co-polymer, blend or mixture thereof. 
     
     
         19 . The composite structure  claim 18 , wherein the co-polymer comprises poly(L-lactic acid) and poly(glycolic acid). 
     
     
         20 . The composite structure  claim 19 , wherein the co-polymer is poly(DL-lactic-co-glycolic acid) (PLDGA). 
     
     
         21 . The composite structure of  claim 14 , wherein the at least one bioactive agent is a hydrophilic agent, a hydrophobic agent, or a combination thereof. 
     
     
         22 . The composite structure of  claim 21 , wherein the at least one bioactive agent comprises at least one anti-inflammatory agent. 
     
     
         23 . The composite structure of  claim 22 , wherein the at least one anti-inflammatory agent is a non-steroidal anti-inflammatory agent or a steroidal anti-inflammatory agent, or a combination thereof. 
     
     
         24 . The composite structure of  claim 23 , wherein the at least one non-steroidal anti-inflammatory agent is an oxicam, a salicylate, an acetic acid derivative of salicylate, a fenamate, a propionic acid derivative of fenamate, or a pyrazole. 
     
     
         25 . The composite structure of  claim 24 , wherein the at least one propionic acid derivative of fenamate is ibuprofen, naproxen, benoxaprofen, flurbiprofen, ketoprofen, fenoprofen, fenbufen, indopropfen, pirprofen, carprofen, oxaprozin, pranoprofen, miroprofen, tioxaprofen, suprofen, alminoprofen, or tiaprofenic. 
     
     
         26 . The composite structure of  claim 24 , wherein the at least one propionic acid derivative of fenamate is ibuprofen. 
     
     
         27 . The composite structure of  claim 24 , wherein the at least one acetic acid derivative of salicylate is diclofenac, fenclofenac, indomethacin, sulindac, tolmetin, isoxepac, furofenac, tiopinac, zidometacin, acematacin, fentiazac, zomepirac, clindanac, oxepinac, felbinac, or ketorolac. 
     
     
         28 . The composite structure of  claim 24 , wherein the at least one acetic acid derivative of salicylate is diclofenac. 
     
     
         29 . The composite structure of  claim 23 , wherein the at least one steroidal anti-inflammatory agent is a corticosteroid. 
     
     
         30 . The composite structure of  claim 29 , wherein the at least one corticosteroid is hydrocortisone, hydroxyltriamcinolone, alphamethyl dexamethasone, dexamethasone-phosphate, beclomethasone dipropionate, clobetasol valerate, desonide, desoxymethasone, desoxycorticosterone acetate, dexamethasone, dichlorisone, diflorasone diacetate, diflucortolone valerate, fluadrenolone, fluclorolone acetonide, fludrocortisone, flumethasone pivalate, fluosinolone acetonide, fluocinonide, flucortine butylesters, fluocortolone, fluprednidene (fluprednylidene) acetate, flurandrenolone, halcinonide, hydrocortisone acetate, hydrocortisone butyrate, methylprednisolone, triamcinolone acetonide, cortisone, cortodoxone, flucetonide, fludrocortisone, difluoro sane diacetate, fluradrenolone, fludrocortisone, diflurosane diacetate, fluradrenolone acetonide, medrysone, amcinafel, amcinafide, betamethasone, a betamethasone ester, chloroprednisone, chlorprednisone acetate, clocortelone, clescinolone, dichlorisone, diflurprednate, flucloronide, flunisolide, fluoromethalone, fluperolone, fluprednisolone, hydrocortisone valerate, hydrocortisone cyclopentylpropionate, hydrocortamate, meprednisone, paramethasone, prednisolone, prednisone, beclomethasone dipropionate, or triamcinolone. 
     
     
         31 . The composite structure of  claim 30 , wherein the at least one corticosteroid is betamethasone or dexamethasone.