Abstract:
The present disclosure provides implants suitable for drug delivery. In embodiments, the present disclosure provides layered biodegradable drug delivery implants and systems and methods for making these implants.

Description:
BACKGROUND 
     1. Technical Field 
     The present disclosure generally relates to drug delivery implants. More particularly, the present disclosure relates to layered biodegradable drug delivery implants and systems and methods for making the implants. 
     2. Background of Related Art 
     Many therapeutic agents (TAs) and active pharmaceutical ingredients (APIs) are known. As discussed in U.S. Pat. No. 6,632,457 the entire disclosure of which is incorporated by reference herein, hydrogels may be used to form delivery implants for the controlled release of TAs and APIs. These drug delivery implants are typically preformed, and thus, provided to a clinician with one or more predetermined TAs and/or APIs, in predetermined concentrations, configured to be dispensed at predetermined rates. 
     Customizing an implant for a given patient and/or procedure using current implant forming methods may thus be cost and/or time prohibitive. Further, many TAs and/or APIs begin to denature upon formation, thus limiting the shelf-life of an implant and/or the agents and/or ingredients that may be used in the implant. 
     Improved systems and methods for making drug delivery implants that may be preformed, i.e., in an operating room during a surgical procedure, remain desirable. 
     SUMMARY 
     The present disclosure provides systems for forming implants, methods for forming such implants, as well as implants formed thereby. In embodiments, a system of the present disclosure includes a system for forming a coaxial implant including a first assembly for dispensing a first material; a second assembly for dispensing a second material; a sleeve defining first and second ends and defining a cavity therebetween for forming an implant, wherein the first and second ends are configured for operable engagement with each of the first and second assemblies; and a centering post configured for operable engagement with the sleeve. 
     A method of the present disclosure includes, in embodiments, a method of forming a coaxial implant including providing a system including first and second dispensing assemblies, an implant forming sleeve having two ends, and a centering post; selectively securing the first dispensing assembly and the centering post with a first end of the implant forming sleeve; activating the first dispensing assembly to deposit a first material within the sleeve and about the centering post to form a first layer of the implant; separating the centering post from the sleeve; selectively securing the second dispensing assembly with a second end of the implant forming sleeve; activating the second dispensing assembly to deposit a second material within the sleeve to form a core of the implant; and separating the first and second dispensing assemblies from the sleeve. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments of the disclosure and, together with a general description of the disclosure given above, and the detailed description of the embodiment(s) given below, serve to explain the principles of the disclosure, wherein: 
         FIG. 1  is side view of a coaxial implant according to an embodiment of the present disclosure; 
         FIG. 2  is a cross-sectional view of the implant of  FIG. 1  taken along line  2 - 2  of  FIG. 1 ; 
         FIG. 3  is a side view of an implant according to an alternative embodiment of the present disclosure; 
         FIG. 4  is a top view of a system for forming a coaxial implant according to an embodiment of the present disclosure; 
         FIGS. 5A-5J  are end views of sleeves according to alternative embodiments of the present disclosure; 
         FIGS. 6A-6D  are side views of sleeves according to alternative embodiments of the present disclosure; 
         FIG. 7  is a perspective view of the implant forming system of  FIG. 4 , including a sleeve operably engaged with a first dispensing assembly and a centering post; 
         FIG. 8  is a perspective view of the system, including the sleeve, dispensing assembly and post of  FIG. 7  following activation of the dispensing assembly; 
         FIG. 9  is a perspective view of a centering plug shown in  FIG. 7  removed from the sleeve; 
         FIG. 10  is a perspective view of a second dispensing assembly engaged with the sleeve; 
         FIG. 11  is a perspective view of the first and second dispensing assemblies and sleeve of  FIG. 10  following activation of the second dispensing assembly; 
         FIG. 12  is a perspective view of the sleeve shown in  FIGS. 7-11 ; 
         FIG. 13  is a perspective view of the sleeve of  FIG. 12  and a coaxial implant formed within the sleeve; 
         FIG. 14  is a perspective view of the coaxial implant of  FIG. 13 ; and 
         FIG. 15  is cross-section end view of another embodiment of an implant according to the present disclosure. 
     
    
    
     DETAILED DESCRIPTION 
     Referring initially to  FIGS. 1 and 2 , a delivery implant according to an embodiment of the present is shown generally as implant  10 . Implant  10  includes a core  20 , a first layer or coating  30 , a second layer or coating  40 , a third layer or coating  50 , and a fourth layer or overcoat  60 . First layer  30  is formed about core  20 . Second layer  40  is formed about first layer  30 . Third layer  50  is formed about second layer  40 . Overcoat  60  is formed about third layer  50 . As shown, each of first layer  30 , second layer  40 , third layer  50  and overcoat  60  fully encase respective core  20 , first layer  30 , second layer  40  and third layer  50 . In this manner, each of overcoat  60 , third layer  50 , second layer  40  and first layer  30  must degrade before each subsequent inner layer is exposed. 
     In embodiments, any or all of core  20 , first layer  30 , second layer  40 , and third layer  50  may extend the entire length of one or more of the subsequent outer layers, thereby exposing one or both of the ends thereof. As will be discussed in further detail below, the exposed ends may allow for coaxial degradation of the layer. 
     Although shown including a core, three (3) layers and an overcoat, it is envisioned that implant  10  may include a core and more or less than 3 layers. In embodiments, implant  10  does not include an overcoat  60 . 
     Each of first, second and third layers  30 ,  40 ,  50 , and overcoat  60 , may be of equal or different thicknesses. In this manner, each of first, second and third layers  30 ,  40 ,  50  and overcoat  60  may degrade at the same or different rates. As shown, implant  10  and core  20  include a substantially cylindrical body having a circular cross-sectional shape. It is envisioned that either or both of implant  10  and core  20  may include alternative cross-sectional shapes, e.g., square, pentagonal, octagonal. It is further envisioned that core  20  may include one or more radial projections or may be otherwise configured to modify the degradation rate of implant  10  in general, and core  20 , specifically. 
     With reference still to  FIGS. 1 and 2 , each of core  20 , first layer  30 , second layer  40 , third layer  50  and overcoat  60  may include one or more polymers and/or one or more hydrogels. The hydrogels may be based upon natural materials, synthetic materials, combinations thereof, and the like. In embodiments, suitable hydrogels include those using synthetic precursors within the purview of those skilled in the art, e.g., as used in commercially available products such as FOCALSEAL® (Genzyme, Inc.), COSEAL® (Angiotech Pharmaceuticals), and DURASEAL® (Confluent Surgical, Inc). Other suitable hydrogels include, for example, those disclosed in U.S. Pat. Nos. 6,656,200; 5,874,500; 5,543,441; 5,514,379; 5,410,016; 5,162,430; 5,324,775; 5,752,974; and 5,550,187. 
     In addition to the above hydrogels, an implant formed in accordance with the present disclosure may include other biocompatible polymers. Suitable biocompatible polymers may also be natural or synthetic materials. In embodiments, the biocompatible polymers may be biodegradable. Biodegradable materials include natural collagenous materials, cat gut, celluloses, including carboxymethyl cellulose, and/or hyaluronic acid, as well as synthetic resins including those derived from alkylene carbonates, trimethylene carbonate, tetramethylene carbonate, caprolactone, valerolactone, dioxanone, polyanhydrides, polyesters, polyacrylates, polymethylmethacrylates, polyurethanes, glycolic acid, lactic acid, glycolide, lactide, polyhydroxy butyrates, polyorthoester, polyhydroxy alkanoates, homopolymers thereof, copolymers thereof, combinations thereof, and the like. For example, in embodiments, In embodiments, overcoat  60  may be formed of an absorbable material such as cellulose. 
     The type and/or composition of the polymer and/or hydrogel used in each of core  20 , layers  30 ,  40 ,  50 , and overcoat  60 , may be the same or different. The hydrogels used to form implant  10  may be hydrated or dehydrated. Each of core  20 , layers  30 ,  40 ,  50 , and overcoat  60 , may further include one or more therapeutic agents (TAs) and/or one or more active pharmaceutical ingredients (APIs). The one or more TAs and/or one or more APIs used in each of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60 , and the concentration of each, may be the same or different. A polymeric coating (not shown) may be provided between one or more of core  20 , first layer  30 , second layer  40 , third layer  50  and overcoat  60 . For example, in embodiments, polylactide, or a polylactide-co-glycolide coating may be provided between one or more of core  20 , first layer  30 , second layer  40 , third layer  50  and overcoat  60 . It is envisioned that the polymeric coating between layers may impart hydrophobocity to reduce the swell time of each layer,  30 ,  40 ,  50 , as well as overcoat  60 . The polymeric coating between layers may also provide support to implant  10 . 
     As discussed above, one or more of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60 , of implant  10  may include exposed first and/or second ends. Either or both of ends  12 ,  14  of implant  10  may be dipped into a polymeric material to seal either or both of the first and second ends of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60 . Sealing ends  12 ,  14  of implant  10  ensures that the release of the one or more TAs and/or one or more APIs contained within each of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60 , may be radial or tangential. 
     Turning briefly to  FIG. 3 , in an alternative embodiment, each of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60 , extends the length of implant  10 . As shown, ends  12 ,  14  of implant  10  are left open, thereby exposing both ends of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60 . In this manner, the one or more TAs and/or APIs in each of core  20 , first, second and third layers  30 ,  40 ,  50 , and overcoat  60  may be released longitudinally from implant  10 . In embodiments, it is envisioned that only one of the ends  12 ,  14  may be sealed (not shown) to allow for slower longitudinal radial release of the one or more TAs and/or APIs from implant  10 . 
     A system for forming a coaxially layered cylindrical implant will now be described with reference to  FIGS. 4-12 . Referring initially to  FIG. 4 , implant forming system  100  includes at least a first dispensing assembly  200 , a second dispensing assembly  300 , an implant forming sleeve  400 , and a centering post  500 . Although the system of the present disclosure will be described as relates to a system for forming a coaxially-layered, cylindrical shaped implant  10   a  ( FIG. 12 ) having a core  20   a  and a first layer  30   a , as will be discussed in further detail below, implant forming system  100  may be modified for use in forming an implant having multiple layers. Additionally, implant forming system  100  may be modified to form an implant having multiple cores  20   b  ( FIG. 13 ) and/or having different cross-sectional profiles. 
     With reference still to  FIG. 4 , first and second dispensing assemblies  200 ,  300  may include any known assemblies capable of dispensing a material or composition through a distal tip. As shown, first and second dispensing assemblies  200 ,  300  are substantially similar; however, it is envisioned that first and second dispensing assemblies  200 ,  300  may be different. Each of first and second dispensing assemblies  200 ,  300  include respective first and second sources of component  202 ,  302 ,  204 ,  304  and a mixing tip  206 ,  306 , respectively. 
     Although shown including dispensing assemblies having two sources of component and a mixing tip, it is envisioned that dispensing assemblies having alternative configurations may be used with implant forming system  100 . For example, either or both of dispensing assemblies  200 ,  300  may include only a single source of component and a polymerizing tip that is configured to activate the component as the component passes through the tip. Alternatively, dispensing assemblies  200 ,  300  may be configured to mix more than two components. 
     As shown, the first and second sources of components  202 ,  302 ,  204 ,  304  include syringes; however, it is envisioned that other sources of component may be employed. For example, components may be supplied to sleeve  400  using metering pumps, squeeze bags or other dispensing means. It is further envisioned that dispensing assemblies  200 ,  300  may be configured to mix one or more powdered components with one or more liquid components. Distal ends  208 ,  308  of mixing tips  206 ,  306  of respective first and second dispensing assemblies  200 ,  300  are configured to selectively engage either end  404 ,  406  of sleeve  400  using any suitable method, including bayonet coupling, friction fit, threads, combinations thereof, and the like. 
     Still referring to  FIG. 4 , implant forming sleeve  400  defines an elongated, substantially annular member  402  having first and second ends  404 ,  406  and defining a longitudinal cavity  403  therebetween. Although shown having a circular cross-section, it is envisioned that sleeve  400  may have a cross-section that is rectangular ( FIG. 5A ), star-shaped ( FIG. 5B ), octagonal, ( FIG. 5C ), hexagonal ( FIG. 5D ), oval ( FIG. 5E ), triangular ( FIG. 5F ), pentagonal ( FIG. 5G ), diamond ( FIG. 5H ), trapezoidal ( FIG. 5I ), cross-shaped ( FIG. 5J ), or any other suitable configuration, including concave or convex (not shown). Although shown having a substantially cylindrical profile, it is envisioned that sleeve  400  may have alternative profiles including, for example, sleeve  400  may be oblong ( FIG. 6A ), barbell-shaped ( FIG. 6B ), stepped ( FIG. 6C ), curved ( FIG. 6  D), or any other suitable configuration. Each of first and second ends  404 ,  406  is configured for selective engagement with distal ends  208 ,  308  of respective first and second dispensing assemblies  200 ,  300 . Sleeve  400  may be formed of paper, plastic or polymer. Although, in one embodiment, sleeve  400  is intended to be removed from implant  10  after formation, sleeve  400  may be composed of a degradable material that may remain about implant  10  following implantation. In this manner, sleeve  400  provides an additional layer to implant  10 . It is envisioned that the degradable sleeve may be infused with one or more TA and/or API to improve the characteristics of implant  10 . In another embodiment, and as shown, sleeve  400  includes one or more zippers  405  ( FIG. 10 ) or perforations formed along a length thereof configured for creating a longitudinal seam  405   a  ( FIG. 11 ) in sleeve  400  such that sleeve  400  may be separated and removed from implant  10 . Although not shown, it is envisioned that one or more polymeric layers including one or more TAs and/or APIs may be provided in sleeve  400  prior to forming an implant, such that an implant formed using the sleeve would include one or more extra layers to improve the characteristics of the implant. 
     In embodiments, an additional layer may include a second sleeve (not shown) within or surrounding sleeve  400 . The multiple sleeves may, in embodiments, be formed of the same or different materials forming sleeve  400 , including the same or different TAs and/or APIs. In some embodiments, the multiple sleeves may provide a core/shell configuration to the implant. 
     Each of first and second ends  404 ,  406  are further configured to selectively engage a base portion  502  of centering post  500 . With reference still to  FIG. 4 , centering post  500  is configured to be received within cavity  403  of sleeve  400  and to selectively engage an end  404 ,  406  thereof. Centering post  500  includes a base  502  and a post  504  extending from base  502 . Base  502  includes a handle portion  502   a  on a proximal end thereof and a plug portion  502   b  on a distal end thereof. Handle portion  502   a  is configured to facilitate engagement of centering post  500  by a clinician. Plug portion  502   b  is configured for selective engagement with an end  404 ,  406  of sleeve  400 . As will be discussed in further detail below, plug portion  502   b  of base  502  effectively seals an end  404 ,  406  of sleeve  400  to retain components within sleeve  400  until the components have had sufficient time to harden. Post  504  of centering post  500  is configured to create a longitudinal void (not shown) within first layer  30   a  ( FIG. 12 ) of implant  10   a  during formation of first layer  30   a  upon which a second material may be added to form core  20   a . Post  504  may extend the entire length of sleeve  400  or may only extend partially therethrough. In another embodiment, post  504  may be composed of a biodegradable material and include one or more TAs and/or APIs configured for controlled release. In this manner, post  504  may include a breakaway connection such that post  504  may remain within implant  10  after forming of first layer  30   a  so that post  504  becomes core  20   a.    
     The use of implant forming system  100  will now be described with reference to  FIGS. 7-14 . Referring initially to  FIG. 7 , first dispensing assembly  200  is selectively connected with first end  404  of implant forming sleeve  400  and centering post  500  is selectively received within second end  406  of sleeve  400 . First dispensing assembly  200  may be provided with first and second sources of component  202 ,  204 , respectively, or instead, first and second sources of component may be added to dispensing assembly  200  prior to forming first layer  30   a  of implant  10   a  ( FIG. 14 ). In this manner, the components and resulting first layer  30   a  may be customized for a given procedure. First and second components  202 ,  204 , which form first layer  30   a  of implant  10   a  may include one or more polymeric materials, one or more hydrogels, one or more TAs and/or one or more APIs. Such materials may be activated upon combination or as the resulting mixture passes through mixing tip  206 . 
     Turning to  FIG. 8 , activation of dispensing assembly  200  causes the contents thereof to pass through mixing tip  206  and out distal outlet  208  into cavity  403  of sleeve  400  about post  504  of centering post  500 . Activation of dispensing assembly  200  may include powering a mixing assembly, activating a polymerizing light, and/or simply depressing first and second plungers, as indicated by arrows “A” in  FIG. 7 , to cause the flow of first and second components through mixing tip  208  and into sleeve  400 . As discussed above, plug portion  502   b  of base  502  of centering post  500  securely engages end  406  of sleeve  400  thereby sealing end  406  and preventing the material forming first layer  30   a  from leaking from cavity  403  of sleeve  400 . 
     With reference now to  FIG. 9 , once the material forming first layer  30   a  hardens sufficiently, centering post  500  is separated from second end  406  of sleeve  400  thereby removing post  504  from with cavity  403  thereof. Separation of centering post  500  from sleeve  400  creates a void (not shown) within first layer  30   a  where post  504  once occupied. In an alternative embodiment, centering post  500  may including more than one post  504 . As such, the removal of centering post  500  would create more than one void within first layer  30   a.    
     Turning now to  FIG. 10 , second dispensing assembly  300  is then selectively attached to second end  406  of sleeve  400 . Dispensing assembly  300  is operated in a substantially similar manner to dispensing assembly  200 . Activation of dispensing assembly  300 , as indicated by arrows “B”, causes the contents thereof to pass through mixing tip  306  and into the void (not shown) within sleeve  400  created by the removal of centering post  500 . Depending on the length of post  504  of centering post  500 , dispensing assembly  200  may seal first end  404  of sleeve  400  while second dispensing assembly  300  seals second end  406  thereof. 
     With reference briefly to  FIG. 11 , once the materials forming core  20   a  have been received with first layer  30   a  of implant  10   a , first and second dispensing assemblies  200 ,  300  remain engaged with sleeve  400  until the materials have sufficiently hardened, i.e., such that neither material leaks from sleeve  400  upon disengagement of either first or second dispensing assemblies  200 ,  300 . 
     Turning now to  FIG. 12 , once both core  20   a  and first layer  30   a  have sufficiently hardened, first and second dispensing assemblies  200 ,  300 , are disengaged from sleeve  400 . Core  20   a  and first layer  30   a  may require additional time to harden within sleeve  400  before sleeve  400  is removed. As discussed above, in one embodiment, sleeve  400  is configured to remain on implant  10   a.    
     With reference now to  FIG. 13 , once core  20   a  and first layer  30   a  have sufficiently hardened, sleeve  400  may be separated and removed therefrom. Sleeve  400  is separated from implant  10   a  by pulling on zipper  405  to create seam  405   a  in sleeve  400 . Sleeve  400  may then be peeled off of implant  10   a . As discussed above, in an alternative embodiment, sleeve  400  may be configured to remain on implant  10   a.    
     With reference to  FIG. 14 , implant  10   a  includes core  20   a  extending the entire length thereof and first layer  30   a  coaxially received about core  20   a . Implant  10   a  is then ready for implantation. Alternatively, implant  10   a  may be further treated. For example, implant  10   a  may be dipped in a polymeric material to create a protective overcoat. Either or both of first and second ends  12   a ,  14   a  of implant  10   a  may be sealed to prevent premature coaxial release of core  20   a.    
     It is envisioned that implant forming system  100  may further include one or more additional sleeves (not shown) and/or one or more additional dispensing assemblies (not shown). Each additional sleeve and/or dispensing assembly may be used to provide implant  10   a  with an additional layer of material. 
     With reference to  FIG. 15 , an implant constructed in accordance with an alternative embodiment of a system for forming an implant is shown generally as implant  10   b . Implant  10   b  includes multiple cores  20   b . Cores  20   b  may be formed of the same or different materials. It is envisioned that multiple core implant  10   b  may be formed using a modified centering post having multiple posts. Each of the posts forming the modified centering post may be removed individually to create individual voids. Initially, layer  30   b  is formed about each of the posts as described above, by activating a first dispensing assembly. Once first layer  30   b  has sufficiently hardened, a first of the posts is removed to create a first void within first layer  30   b . The first dispensing assembly may then be removed from a first end of the sleeve and replaced by a second dispensing assembly. The second dispensing assembly may then be activated to deposit a material with the first void. Once this material has sufficient hardened, a second of the posts is removed from the sleeve to create a second void in the first layer. The second dispensing assembly may then be removed from the first end of the sleeve and be replaced by a third dispensing assembly for depositing another material within the second void. This process may be repeated to create an implant having any number of cores  20   b.    
     As noted above, the implant of the present disclosure may be utilized to deliver one or more therapeutic agents (TAs) and/or one or more active pharmaceutical ingredients (APIs) which may, in embodiments, be collectively referred to herein as “bioactive agents.” The term “bioactive agent”, as used herein, is used in its broadest sense and includes any substance or mixture of substances that have clinical use. Consequently, bioactive agents may or may not have pharmacological activity per se, e.g., a dye. Alternatively a bioactive agent could be any agent, which provides a therapeutic or prophylactic effect, a compound that affects or participates in tissue growth, cell growth, cell differentiation, an anti-adhesive compound, a compound that may be able to invoke a biological action such as an immune response, or could play any other role in one or more biological processes. It is envisioned that the bioactive agent may be applied to the present implant in any suitable form of matter, e.g., films, powders, liquids, gels and the like. 
     Examples of classes of bioactive agents, which may be utilized in accordance with the present disclosure for example, include: anti-adhesives; antimicrobials; analgesics; antipyretics; anesthetics; antiepileptics; antihistamines; anti-inflammatories; cardiovascular drugs; diagnostic agents; sympathomimetics; cholinomimetics; antimuscarinics; antispasmodics; hormones; growth factors; muscle relaxants; adrenergic neuron blockers; antineoplastics; immunogenic agents; immunosuppressants; gastrointestinal drugs; diuretics; steroids; lipids; lipopolysaccharides; polysaccharides; platelet activating drugs; clotting factors; and enzymes. It is also intended that combinations of bioactive agents may be used. 
     Anti-adhesive agents can be used to prevent adhesions from forming between the implant and the surrounding tissues to which the implant is applied. In addition, anti-adhesive agents may be used to prevent adhesions from forming between the formed implant and the sleeve described above. Some examples of these agents include, but are not limited to hydrophilic polymers such as poly(vinyl pyrrolidone), carboxymethyl cellulose, hyaluronic acid, polyethylene oxide, poly vinyl alcohols, and combinations thereof. 
     Suitable antimicrobial agents, which may be included as a bioactive agent include: triclosan, also known as 2,4,4′-trichloro-2′-hydroxydiphenyl ether; chlorhexidine and its salts, including chlorhexidine acetate, chlorhexidine gluconate, chlorhexidine hydrochloride, and chlorhexidine sulfate; silver and its salts, including silver acetate, silver benzoate, silver carbonate, silver citrate, silver iodate, silver iodide, silver lactate, silver laurate, silver nitrate, silver oxide, silver palmitate, silver protein, and silver sulfadiazine; polymyxin; tetracycline; aminoglycosides, such as tobramycin and gentamicin, rifampicin, bacitracin, neomycin, chloramphenicol, and miconazole; quinolones such as oxolinic acid, norfloxacin, nalidixic acid, pefloxacin, enoxacin and ciprofloxacin; penicillins such as oxacillin and pipracil; nonoxynol 9; fusidic acid; cephalosporins; and combinations thereof. In addition, antimicrobial proteins and peptides such as bovine lactoferrin and lactoferricin B may be included as a bioactive agent. 
     Other bioactive agents, which may be included as a bioactive agent include: local anesthetics; non-steroidal antifertility agents; parasympathomimetic agents; psychotherapeutic agents; tranquilizers; decongestants; sedative hypnotics; steroids; sulfonamides; sympathomimetic agents; vaccines; vitamins; antimalarials; anti-migraine agents; anti-parkinson agents such as L-dopa; anti-spasmodics; anticholinergic agents (e.g., oxybutynin); antitussives; bronchodilators; cardiovascular agents, such as coronary vasodilators and nitroglycerin; alkaloids; analgesics; narcotics such as codeine, dihydrocodeinone, meperidine, morphine and the like; non-narcotics, such as salicylates, aspirin, acetaminophen, d-propoxyphene and the like; opioid receptor antagonists, such as naltrexone and naloxone; anti-cancer agents; anti-convulsants; anti-emetics; antihistamines; anti-inflammatory agents, such as hormonal agents, hydrocortisone, prednisolone, prednisone, non-hormonal agents, allopurinol, indomethacin, phenylbutazone and the like; prostaglandins; cytotoxic drugs; chemotherapeutics, estrogens; antibacterials; antibiotics; anti-fungals; anti-virals; anticoagulants; anticonvulsants; antidepressants; antihistamines; and immunological agents. 
     Other examples of suitable bioactive agents, which may be delivered by an implant of the present disclosure include, for example, viruses and cells; peptides, polypeptides and proteins, as well as analogs, muteins, and active fragments thereof; immunoglobulins; antibodies; cytokines (e.g., lymphokines, monokines, chemokines); blood clotting factors; hemopoietic factors; interleukins (IL-2, IL-3, IL-4, IL-6); interferons (β-IFN, α-IFN and γ-IFN); erythropoietin; nucleases; tumor necrosis factor; colony stimulating factors (e.g., GCSF, GM-CSF, MCSF); insulin; anti-tumor agents and tumor suppressors; blood proteins such as fibrin, thrombin, fibrinogen, synthetic thrombin, synthetic fibrin, synthetic fibrinogen; gonadotropins (e.g., FSH, LH, CG, etc.); hormones and hormone analogs (e.g., growth hormone); vaccines (e.g., tumoral, bacterial and viral antigens); somatostatin; antigens; blood coagulation factors; growth factors (e.g., nerve growth factor, insulin-like growth factor); bone morphogenic proteins; TGF-B; protein inhibitors; protein antagonists; protein agonists; nucleic acids, such as antisense molecules, DNA, RNA, RNAi; oligonucleotides; polynucleotides; and ribozymes. 
     The implant of the present disclosure may also include, for example, biologically acceptable plasticizers, antioxidants, and/or colorants, which can be impregnated into the medical device. 
     Although the illustrative embodiments of the present disclosure have been described herein with reference to the accompanying drawings, it is to be understood that the disclosure is not limited to those precise embodiments, and that various other changes and modifications may be effected therein by one skilled in the art without departing from the scope or spirit of the disclosure. For example, a first longitudinal section of the core and/or any or all of the layers may be formed of a different composition than one or more subsequent longitudinal sections of the core and/or any or all of the layers.