Drug delivery methods, structures, and compositions for nasolacrimal system

Abstract

An implant for insertion into a punctum of a patient comprises a body. The body has a distal end, a proximal end, and an axis therebetween. The distal end of the body is insertable distally through the punctum into the canalicular lumen. The body comprises a therapeutic agent included within an agent matrix drug core. Exposure of the agent matrix to the tear fluid effects an effective therapeutic agent release into the tear fluid over a sustained period. The body has a sheath disposed over the agent matrix to inhibit release of the agent away from the proximal end. The body also has an outer surface configured to engage luminal wall tissues so as to inhibit expulsion when disposed therein. In specific embodiments, the agent matrix comprises a non-bioabsorbable polymer, for example silicone in a non-homogenous mixture with the agent.

1 - 53 . (canceled) 
     
     
         54 . A punctal plug configured for insertion into a lacrimal canaliculus of a patient for treating dry eye comprising:
 a silicone plug body comprising a cavity;   a drug insert disposed in the cavity, wherein the drug insert comprises:   a drug core comprising a therapeutic agent selected from an immunosuppressive agent, a lubricant, a surfactant, a peptide, a protein, or an enzyme and a polymeric matrix; and   an impermeable sheath body partially covering the drug core, wherein the sheath body is configured to provide an exposed proximal end of the drug core in direct contact with tear fluid that releases therapeutic agent to the eye when the punctal plug is placed in the lacrimal canaliculus of a patient.   
     
     
         55 . The punctal plug of  claim 54 , wherein the therapeutic agent is a lubricant or a surfactant. 
     
     
         56 . The punctal plug of  claim 54 , wherein the therapeutic agent is cyclosporine. 
     
     
         57 . The punctal plug of  claim 54 , wherein the therapeutic agent is a corticosteroid. 
     
     
         58 . The punctal plug of  claim 54 , wherein a distal end of the drug core is sealed with a medical grade adhesive. 
     
     
         59 . The punctal plug of  claim 54 , wherein the polymeric matrix comprises silicone, acrylate, polyethylene, polyurethane, polyester, polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lactic acid) (PLLA), poly(L-glycolic acid) (PLGA), polyglycolide, poly-L-lactide, poly-D-lactide, poly(amino acids),_polydioxanone, polycaprolactone, polygluconate, polylactic acid-polyethylene oxide copolymers, modified cellulose, collagen, polyorthoesters, polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxy acid) or combinations thereof. 
     
     
         60 . The punctal plug of  claim 54 , wherein the drug core further comprises one or more additives to increase or decrease solubility of the therapeutic agent for control of release of the therapeutic agent. 
     
     
         61 . The punctal plug of  claim 54 , wherein the drug core is configured to provide a dose of the therapeutic agent for a period from one month to 3 months. 
     
     
         62 . The punctal plug of  claim 60 , wherein the one or more additives is selected from the group consisting of surfactants, tinuvin, salts and water. 
     
     
         63 . A punctal plug configured for insertion into a lacrimal canaliculus of a patient for treating pre- or post-operative pain comprising:
 a silicone plug body comprising a cavity;   a drug insert disposed in the cavity, wherein the drug insert comprises:   a drug core comprising a therapeutic agent selected from a non-steroidal anti-inflammatory drug (NSAID), an anti-inflammatory agent, an immunosuppressive agent, a lubricant, a surfactant, a peptide, a protein, or an enzyme and a polymeric matrix; and   an impermeable sheath body partially covering the drug core, wherein the sheath body is configured to provide an exposed proximal end of the drug core in direct contact with tear fluid that releases therapeutic agent to the eye when the punctal plug is placed in the lacrimal canaliculus of a patient.   
     
     
         64 . The punctal plug of  claim 63 , wherein the therapeutic agent is selected from a non-steroidal anti-inflammatory drug (NSAID). 
     
     
         65 . The punctal plug of  claim 63 , wherein the therapeutic agent is a corticosteroid. 
     
     
         66 . The punctal plug of  claim 63 , wherein the therapeutic agent is dexamethasone. 
     
     
         67 . The punctal plug of  claim 63 , wherein a distal end of the drug core is sealed with a medical grade adhesive. 
     
     
         68 . The punctal plug of  claim 63 , wherein the polymeric matrix comprises silicone, acrylate, polyethylene, polyurethane, polyester, polyglycolic acid (PGA), polylactic acid (PLA), poly(L-lactic acid) (PLLA), poly(L-glycolic acid) (PLGA), polyglycolide, poly-L-lactide, poly-D-lactide, poly(amino acids),_polydioxanone, polycaprolactone, polygluconate, polylactic acid-polyethylene oxide copolymers, modified cellulose, collagen, polyorthoesters, polyhydroxybutyrate, polyanhydride, polyphosphoester, poly(alpha-hydroxy acid) or combinations thereof. 
     
     
         69 . The punctal plug of  claim 63 , wherein the drug core further comprises one or more additives to increase or decrease solubility of the therapeutic agent for control of release of the therapeutic agent. 
     
     
         70 . The punctal plug of  claim 63 , wherein the drug core is configured to provide a burst dose of the therapeutic agent. 
     
     
         71 . The punctal plug of  claim 63 , wherein the drug core is configured to provide a dose of the therapeutic agent for a period from two days to one month.