Abstract:
The present invention is related to a polymeric vehicle for delivery of bioactive agents, and preferably, for the delivery of one or more bioactive agents. The invention is also directed to a percutaneous device securing and drug delivery device comprising, as a component thereof, a material which delivers antimicrobial and/or other wound-healing factors at the site of the insertion of the catheter into the body. The device, when applied as described herein, provides complete anti-microbial coverage around the entry point of a percutaneous device and, preferably for a length greater than the diameter of the device. The present invention is also directed to methods for using such devices in combination with percutaneous devices primarily to reduce site infections.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention is related to a polymeric delivery vehicle for delivery of bioactive agents, and preferably, for the delivery of one or more bioactive agents. The invention is also directed to a percutaneous device securing and drug delivery device comprising, as a component thereof, a material which delivers antimicrobial and/or other wound-healing factors at the site of the insertion of the catheter into the body. The device, when applied as described herein, provides complete (360 degree) anti-microbial coverage around the entry point of a percutaneous device and, preferably for a length greater than the diameter of the device. 
       BACKGROUND OF THE INVENTION 
       [0002]    Hospitals employ multiple strategies to prevent and/or reduce infections associated with the use percutaneous medical devices, such as antiseptic preparation of insertion sites, including the initial application of topical anti-microbial solutions such as alcohol or iodine to the insertion sites is known. A further topical ointment after insertion of the device, such as an ointment containing neomycin, polymyxin and bactracin, has been shown to prevent catheter colonization/ infection. 
         [0003]    There have also been attempts to attach a cuff to the catheters, with an anti-microbial agent impregnated in the cuff. A commercially available product sold under the trade mark BIOPATCH® is applied around percutaneous devices to prevent localized infection at the insertion site. This product is a foam material that contains an antimicrobial agent chlorhexidine gluconate. Efforts to coat the catheters with anti-microbial agents are known. 
         [0004]    Recent efforts to use a transparent film dressing to allow a visual check on the insertion site is known see for instance U.S. Pat. No. 5,372,589, issued Dec. 13, 1994 to Davis. 
         [0005]    In addition to infection control, there is a need for percutaneous devices to remain securely in place. Securement device are known, such as U.S. Pat. No. 3,918,446, issued Nov. 11, 1975 to Buttaravoli. The device has an upper and a lower pad, between which the intravenous device is fixed. Since the function of the device is to secure the device to the body, there is a teaching to provide an adhesive material to the bottom of lower pad, and to the bottom of the top pad. There is a mention of providing the adhesive with an antibacterial agent. The device of this patent teaches including a slit in the bottom pad of the dressing, which lies below the intravenous needle or catheter when the device is in place, allowing the intravenous device to remain in contact with the skin, and therefore limiting the infection control of the device. 
         [0006]    U.S. Pat. No. 5,833,665 issued to Matthew Bootman et al. is directed to a wound dressing for percutaneous catheters that is comprised of a crosslinked polymer containing a bioactive agent. It discloses a radial slit that is made in the device so that it can be deployed over an already placed catheter. It also discloses and claims the use of adhesives for securing the device. 
         [0007]    Tegaderm™-CHG is a commercial device designed to reduce the incidence of CRBSI, with the CHG being the anti-microbial agent. The CHG is intended to elute from a pad that is transparent and covered with an adhesive bandage layer. The device fails to provide 360 degree coverage around the insertion site, and thereby cannot optimally reduce the potential for CRBSI. The CHG eluting portion of the device is not placed underneath the catheter which may further limit its effectiveness. A number of other patents are teaching various single slit embodiments, including U.S. Pat. No. 7,137,968; U.S. Pat. No. 5,554,106; U.S. Pat. No. 6,765,122; U.S. Pat. No. 7,723,559; U.S. Pat. No. 4,915,694; U.S. Pat. No. 5,968,000; and U.S. Pat. No. 5,620,419. 
         [0008]    It is an object of the present invention to provide a catheter-securing and drug delivery device which is easily applied and is made of a polymer which serves as a delivery vehicle for controlled release of a bioactive agent entirely around a percutaneous wound site. 
         [0009]    These and other objects of the invention will be apparent from the following description and appended claims, and from practice of the invention. 
       SUMMARY OF THE INVENTION 
       [0010]    The present invention is directed to a percutaneous device dressing for use with a percutaneous medical device that has punctured the skin of a patient and which has a portion of the percutaneous medical device protruding from the skin. One type of such a percutaneous device is a catheter, such as a temporary installed catheter or longer term in-dwelling catheter. The dressing of the present invention is formed of a flexible material and has upper and lower surfaces. The lower surface is the skin facing surface when in use. An optional adhesive layer is disposed on the lower surface of the dressing. The dressing also has a bioactive agent that is incorporated into the flexible material of the dressing and/or onto the surfaces of the dressing. The dressing has a channel within its lower, skin-facing surface that is adapted to surround at least a portion of the percutaneous medical device protruding from the skin. The channel can be formed by any known manufacturing techniques, for example it can be machined into the dressing, cut within the dressing, or molded during the forming of the dressing. The dressing has a shape that substantially completes a perimeter proximate to the percutaneous medical device. The dressing can independently comprise gelatin, collagen, and polysaccharides or combination thereof. The dressing can be made of a hydrogel material or a composite material at least one component of which is a hydrogel. The bioactive agent can be an antimicrobial agent, such as a chlorhexidine compound, for instance chlorhexidine gluconate or chlorhexidine acetate; silver compounds, for instance silver iodide, silver bromide, silver chloride; nano-particulate metallic silver; benzalkonium chloride; polyhexamethylene biguanide (PHMB); triclosan; antibiotics such as metronidazole; alcohol; iodine; or other known antimicrobial compounds and combinations thereof, compatible with skin and useful against a range of microorganisms for example against known skin flora such as for instance  S. aureus  and MRSA. 
         [0011]    The present invention also relates to a method of dressing the puncture site of a percutaneous medical device for a patient using a percutaneous device dressing formed from a flexible material and having upper and lower surfaces, with the lower surface being skin facing in use. The dressing also has a bioactive agent that is incorporated into the dressing and/or onto the lower surfaces of the dressing, wherein the dressing is secured to the surface of skin and optionally to the percutaneous medical device with the help of an optional adhesive layer disposed on the lower surface of the dressing or with a help of an adhesive overdressing layer preferably in a form of adhesive thin film or adhesive bandaging tape. 
         [0012]    The dressing further has a channel within its lower, skin-facing surface that is adapted to surround at least a portion of the percutaneous medical device protruding from the skin. In use, the dressing is applied by positioning the dressing over the percutaneous medical device with the lower surface facing the skin and the percutaneous medical device, so that the channel within the lower surface of the dressing can accept a portion of the percutaneous medical device, and to enable the dressing to surround a portion of a perimeter proximate to the percutaneous medical device at the puncture site. The lower surface of the dressing is thereby in contact with the skin surrounding the puncture site while the channel cut within the lower surface of the dressing is simultaneously in contact with a portion of the medical device protruding from the skin. Advantageously, the dressing enables nurses and physicians to position the dressing over a previously installed or secured percutaneous medical device, such as a catheter. The dressing further provides 360 degree anti-microbial coverage around catheter shaft and for a length greater than the diameter of the catheter shaft. In one embodiment the dressing is elastically resilient, and it can be attached to the catheter without using an adhesive or additional dressing. 
     
    
     
       BRIEF DESCRIPTION OF THE FIGURES 
         [0013]      FIGS. 1   a  and  1   b  illustrate an embodiment of the inventive percutaneous medical device dressing in combination with a medical device that punctures the skin of a patient. 
           [0014]      FIGS. 2   a  and  2   b  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0015]      FIG. 3  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0016]      FIG. 4  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0017]      FIG. 5  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0018]      FIG. 6  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0019]      FIG. 7  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0020]      FIG. 8  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0021]      FIGS. 9   a ,  9   b ,  9   c ,  9   d ,  9   e ,  9   f  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0022]      FIG. 10  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0023]      FIG. 11  illustrates an embodiment of the inventive percutaneous medical device dressing. 
           [0024]      FIGS. 12   a  and  12   b  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0025]      FIGS. 13   a  and  13   b  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0026]      FIGS. 14   a  and  14   b  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0027]      FIGS. 15   a  and  15   b  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0028]      FIGS. 16   a ,  16   b ,  16   c , and  16   d  illustrate an embodiment of the inventive percutaneous medical device dressing. 
           [0029]      FIGS. 17   a  and  17   b  illustrate an embodiment of the inventive percutaneous medical device dressing. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0030]    In a preferred embodiment of the present invention, the dressing is made of a polymeric carrier and a bioactive agent, wherein the bioactive agent is releasable from the polymeric carrier in a controlled manner to a wound or to the skin. 
         [0031]    The percutaneous device dressing further optionally comprises an adhesive, generally disposed on the lower surface of the dressing and optionally within the channel for affixing the dressing to the skin and for affixing the dressing to the percutaneous medical device. 
         [0032]    In another preferred embodiment the polymeric delivery vehicle is in the form of an elastomeric pad with a channel that is used as a wound dressing. The pad may be secured upon a wound by an adhesive water-vapor film over the pad which adheres to the skin area surrounding the wound. 
         [0033]    The percutaneous device dressing of this invention has the advantage of ease of placement without loss of complete perimeter coverage. 
         [0034]      FIGS. 1   a  and  1   b  show two views of the body of dressing  10  in a shape of a pad, the body of dressing  10  having an upper surface  14  and a skin-facing lower surface  12  and further having a channel  20  cut within the body of dressing pad  10  proximal to the lower surface  12 . Also shown is the percutaneous medical device  100 , in the form of a catheter having a proximal end  110  piercing the skin (not shown) and disposed substantially within the patient&#39;s body (not shown) and a distal end  120  disposed substantially on the surface of skin (not shown). Channel  20  has a portion substantially parallel to the lower surface  12  and a portion substantially perpendicular to the lower surface  12  so as to accommodate within channel  20  the percutaneous medical device  100 . The percutaneous medical device  100  is partially enclosed within channel  20  with the area of skin penetration around the proximal end  110  completely covered by the dressing  10  from all sides, to provide complete coverage, maintain coverage over 360 degrees around a central point over percutaneous medical device  100 . 
         [0035]    While the positioning of percutaneous medical device  100  in  FIGS. 1   a  and  1   b  indicates that proximal end  110  piercing the skin is positioned under angle approximately perpendicular to the skin, the angle of percutaneous medical device  100  relative skin will vary depending on type of percutaneous medical device  100  and type of installation, from almost parallel to the skin at the point of entering the skin, to about 90 degrees or perpendicular to the skin. Typical angles can be from about 15 degrees to about 90 degrees as between percutaneous medical device  100  and the skin, such as 15, 30, 60, 80 degree angles. 
         [0036]    Referring now to  FIGS. 1 through 7 , the dimensions of the channel  20  should preferably substantially conform to the size and shape of the percutaneous device  100 . The dimensions of channel  20  generally conform to the dimensions of percutaneous medical device  100  so that there is a loose fit, a snug fit or a snap fit. In certain embodiments the diameter of channel  20  is about 0.95, 1.0, 1.1, or 1.2 times the size of the diameters of the outer surface of percutaneous device  100 . 
         [0037]    Gap  22  represents an opening of the channel  20  on the lower skin-facing surface  12 . As illustrated in  FIGS. 2   a  and  2   b , in one embodiment gap  22  is a narrow slit with the width from about 0.01 mm to about 1 mm, such as 0.1 mm or 0.25 mm. Gap  22  can be positioned symmetrically in the center of channel  20  as shown or can be offset from the center of channel  20 . As illustrated in  FIGS. 1   a,    1   b,    3 ,  4 , and  5 , gap  22  can vary from a narrow slit to a width just under the diameter of the percutaneous medical device  100 . In an illustrative example, gap  22  can vary from about 0.5 mm to about 3.5 mm for percutaneous medical device  100  having an external diameter of 4 mm and channel  20  having diameter of about 3.8 mm, 4.0 mm, or 4.2 mm. As illustrated in  FIG. 6 , gap  22  can also have a width that is approximately equivalent to or slightly greater than the diameter of the outer surface of percutaneous medical device  100  and diameter of channel  20 . 
         [0038]    Referring now to  FIGS. 3 through 6 , an optional circular opening  24  within lower surface  12  is provided to accommodate percutaneous medical device  100 . Optional circular opening  24  is in communication with channel  20 . Embodiments of the present invention without the optional circular opening  24  are shown in  FIGS. 2   a  and  2   b , with side wall of the dressing body shown by numeral  27 . The diameter of circular opening  24  is adapted so as to accommodate percutaneous medical device  100  and can be smaller than, equivalent to, or slightly larger than the diameter of percutaneous medical device  100 . In certain embodiments diameter of circular opening  24  is equivalent to about 0.8, 1.0, or 1.1 diameters of percutaneous medical device  100 . 
         [0039]    Dressing  10  is shown in  FIGS. 1-7  as having generally circular or partially circular shape of the channel  20  that corresponds to a generally circular shape needed to surround a conventional percutaneous medical device. Other shapes of the channel, including elliptical and polygonal shapes, are contemplated provided that the channel  20  can accommodate the percutaneous medical device  100 . 
         [0040]    The outer perimeter of dressing  10  can be substantially circular as shown in  FIGS. 1   a ,  1   b,    2   a,    2   b,  and  3 , or can be different so that when in position, the exterior perimeter is elliptical, square, rectangular or irregularly shaped. Embodiments of square or rectangular shaped dressing  10  are shown in  FIGS. 4 ,  5 , and  6 . Elliptical external shape of dressing  10  is illustrated by  FIG. 7  showing the skin side view of dressing  10  with gap  22  and optional circular opening  24 . Advantageously, the elliptical shape with offset center provides for a longer supporting path for percutaneous medical device  100  and longer path of protection against the ingress of potentially infectious matter along channel  20 . 
         [0041]    In one embodiment, dressing  10  is made of a transparent polymer or transparent or semi-transparent hydrogel thus facilitating positioning of dressing  10  over percutaneous medical device  100 . In one embodiment, only the central portion of the dressing immediately surrounding the skin penetration area is transparent, such as central part of the dressing  10 . 
         [0042]    Dressing  10  is sized to cover a significant portion of catheter or percutaneous medical device  100  that protrudes from the skin, and not just the immediate skin area surrounding the penetration site. In one embodiment, the diameter of circular-shaped dressing  10  or the length of the side of the square-shaped dressing  10  is equal to from about 2 diameters of the outer surface of percutaneous medical device  100  to about 20 times the diameters of the outer surface of percutaneous medical device  100 . In some embodiments the diameter of dressing  10  is equal to about 2, 3, 4, or 5 times the diameters of the outer surface of percutaneous medical device  100 . 
         [0043]    Dressing  10  is applied around catheter or percutaneous medical device  100  with lower surface  12  of dressing  10  facing the percutaneous medical device  100  such that the percutaneous medical device  100  enters channel  20  through gap  22 . 
         [0044]    Referring now to  FIG. 8 , a cross-sectional view of dressing  10  installed on patient&#39;s skin  200  and attached to skin  200  by an optional adhesive layer  26  disposed on skin-facing lower surface  12  of dressing  10  and optionally within channel  20 . Alternatively or in addition to optional adhesive layer  26 , dressing  10  is removably attached to skin  200  by an overdressing  50  in the form of an adhesive tape or bandage applied over dressing  10 . Overdressing  50  can be occlusive or semi-occlusive, such as adhesive tape, bandage, or polyurethane film. 
         [0045]    Referring now to  FIGS. 9   a  and  9   b , an alternative cross-sectional view is shown of dressing  10  that is installed on patient&#39;s skin  200  and removably attached to skin  200  by an optional adhesive layer  26  or overdressing  50  (not shown). Dressing  10  is applied around catheter or percutaneous medical device  100  so that the percutaneous medical device  100  is positioned in and held within channel  20 . 
         [0046]    Dressing  10  completely surrounds the wound or skin puncture site for the percutaneous medical device  100  thus preventing the ingress of contaminating or infectious matter and delivers anti-microbial active ingredient that is disposed within dressing  10 . 
         [0047]    At least the lower surface  12  of the dressing  10  and optionally all surfaces and optionally the body of dressing  10  are provided with an anti-microbial material in order to limit infection. Anti-microbial materials for use with medical dressing materials are well known in the art. The anti-microbial material may be impregnated in dressing  10  or provided as a thin film of an anti-microbial material on the surfaces of dressing  10 , with at least skin-facing lower surface  12  having anti-microbial material. Optionally other surfaces, particularly surfaces of channel  20 , circular opening  24 , and gap  22  are also provided with the anti-microbial material. Optional adhesive layer  26  can also optionally contain anti-microbial material. 
         [0048]    The material comprising drug eluting material of dressing  10  may be, for example, a porous sponge or hydrogel or solid polymeric matrix. Examples of materials include chitosan, polysaccharides, glycosaminoglycans, glycoproteins, proteins, silicones, PVA, alginates, oxidized regenerated cellulose, and other materials known to be capable of either reversibly binding to anti-microbial agents or serving as reservoirs for the diffusion of the anti-microbial agent. 
         [0049]    While the positioning of percutaneous medical device  100  in  FIG. 9   a  indicates that proximal end  110  piercing skin  200  is positioned under angle approximately perpendicular to the skin, the angle of percutaneous medical device  100  relative skin will vary depending on type of percutaneous medical device  100  and type of installation, from almost parallel to the skin at the point of entering the skin, to about 90 degrees or perpendicular to the skin. Typical angles can be from about 15 degrees to about 90 degrees as between percutaneous medical device  100  and the skin surface, such as 15, 30, 60, 80 degree angles. As it is further illustrated in  FIG. 9   b , the angle of percutaneous medical device  100  relative to the skin surface can be about 45 degrees. 
         [0050]    As further illustrated in cross-sectional views of dressing  10  presented in  FIGS. 9   c  and  9   d , channel  20  can optionally have perpendicular connection to circular opening  24 , as shown in  FIG. 9   c , or optional an angular connection to circular opening  24 , as shown in  FIG. 9   d . In the embodiments lacking optional circular opening  24 , as shown in  FIGS. 2   a  and  2   b , percutaneous medical device  100  also can exit channel  20  at any angle from skin-facing lower surface  12 . 
         [0051]    The embodiments shown in  FIGS. 9   e  and  9   f  illustrate a cross-sectional view of dressing  10  with channel  20 , whereas channel  20  has an entrance  28  within side wall  27  and an exit  29  within skin-facing lower surface  12  of dressing  10 . Entrance  28  has substantially the same diameter as channel  20 , and exit  29  has dimensions that are larger than the diameter of channel  20  enabling dressing  10  to accommodate flexible positioning of percutaneous medical device  100  (not shown) in channel  20 , with percutaneous medical device  100  being shaped as needed for optimal ingress into the patient&#39;s body. The design of dressing  10  shown in  FIGS. 9   e  and  9   f  facilitates a smooth bend of catheter or percutaneous medical device within channel  20 , from being substantially parallel to the skin of the patient to an angle required to enter the skin of the patient. 
         [0052]    An embodiment shown in  FIG. 9   f  further illustrates a cross-sectional view of dressing  10  with channel  20 , whereas channel  20  has within side wall  27  entrance  28  with a flared or conical shape having a diameter that is larger at entrance  28  relative to the diameter of channel  20 . Flared or conical shape of entrance  28  facilitates positioning of dressing  10  in a coupled way with connectors or couplers or flanges positioned on catheter or percutaneous medical device  100  (not shown), whereby such connectors or couplers (not shown) installed on percutaneous medical device  100  (not shown) are inserted into flared or conically shaped entrance  28  and are fixedly positioned within entrance  28 . 
         [0053]    Referring now to  FIG. 10 , in one embodiment of the present invention, a small quantity of semi-solid viscous sealant or anti-microbial ointment  40  is disposed in channel  20  prior to applying dressing  10  over catheter or percutaneous medical device  100 . In a preferred embodiment, sealant or anti-microbial ointment  40  is disposed in channel  20  during manufacturing of dressing  10 . 
         [0054]    As illustrated in  FIG. 11 , upon positioning of catheter or percutaneous medical device  100  within channel  20 , the semi-solid sealant or ointment  40  is displaced by the catheter along channel  20  walls and also into gap  22  and seals around catheter  100  and against skin  200 . Semi-solid anti-microbial ointments and sealants are known in the art. Advantageously, sealing channel  20  with ointment  40  provides additional protecting against ingress of contaminating potentially infectious matter along channel  20 . 
         [0055]    An embodiment of the present invention which is shown in  FIG. 12   a  has a compartment  50  cut into lower surface  12  of dressing  10 . Compartment  50  is filled with ointment  40  during manufacturing of dressing  10  and has a connecting channel  52  connecting compartment  50  to gap  22  or to channel  20  opening. After positioning of catheter or percutaneous medical device  100  within channel  20 , the healthcare practitioner depresses upper surface  14  above compartment  50 , with the approximate area of depressing being shown by arrow  56  above compartment  50 , thus displacing ointment  40  through connecting channel  52  into channel  20  resulting in ointment  40  distributing between channel  20  walls and catheter  100  and into gap  22  and advantageously sealing around catheter  100  and against skin  200 , as illustrated in  FIG. 12   b.    
         [0056]    In the embodiments of the present invention shown in  FIGS. 10 ,  11 , and  12 , the ointment or sealant  40  is optionally photo-crosslinkable. Photo-crosslinkable sealants and adhesives are known in the art. Actinic light (such as blue light or UV light) from a light source, such as a hand-held battery-operated or similar light source is then optionally used to cross-link the sealant after installation of dressing  10  over catheter  100  and after ointment or sealant  40  is displaced into channel  20 . Cross-linked ointment or sealant  40  provides additional adhesive strength preventing displacement of dressing  10  against percutaneous medical device  100  and further preventing the ingress of the contamination along channel  20 . 
         [0057]    Referring now to  FIGS. 13   a  and  13   b , an embodiment of the present invention is shown, with  FIG. 13   a  representing a top view and  FIG. 13   b  representing a side view. As shown in  FIGS. 13   a  and  13   b , dressing  10  of a final shape substantially similar to the embodiments of  FIGS. 1 through 12  is formed of two optionally linked subunits, lower portion  300  and upper portion  400 .  FIG. 13   a  illustrates a top view of dressing  10  prior to installation, dressing  10  comprising two foldably linked portions: lower portion  300  having circular cut  320  and slit  310  and upper portion  400  having a surface trench or channel  410 . Lower portion  300  is foldably linked to upper portion  400  at the linking area  330 .  FIG. 13   b  shows an assembled dressing  10  with upper portion  400  folded at linking area  330  and positioned on top of lower portion  300 , with percutaneous medical device or catheter  100  not shown. The resulting dressing  10  assembled of lower portion  300  and upper portion  400  is substantially similar to dressing  10  as shown in  FIGS. 1 through 12 . 
         [0058]    In use, as shown in  FIGS. 14   a  and  14   b , lower portion  300  is installed on percutaneous medical device or catheter  100  with the circular cut  320  surrounding the catheter and slit  310  going around and under the catheter  100 . Percutaneous medical device or catheter  100  can be positioned aligned with slit  310  as shown in  FIG. 14   a  or angular to slit  310 , such as perpendicular to slit  310 , as shown in  FIG. 14   b , with surface trench or channel  410  being also perpendicular to slit  310 . Advantageously, angular positioning of percutaneous medical device or catheter  100  relative to slit  310  further improves the 360 degrees antimicrobial protective action of dressing  10 . 
         [0059]    After positioning lower portion  300  on percutaneous medical device or catheter  100  as shown in  FIGS. 14   a  and  14   b , upper portion  400  is folded at linking area  330  and positioned on top of lower portion  300  with surface channel  410  surrounding and covering percutaneous medical device or catheter  100 . Optionally, an adhesive is disposed on at least one surface of lower portion  300  or upper portion  400  which are facing each other in assembled dressing  10 , to assure structural integrity of assembled dressing  10 . The resulting dressing  10  assembled of lower portion  300  and upper portion  400  is substantially similar to dressing  10  as shown in  FIGS. 1 through 12 . Advantageously, manufacturing of dressing  10  made of two subunits is simplified, whereby low cost web converting and high speed molding processes can be used to manufacture two-piece dressing  10 . 
         [0060]    Referring now to  FIGS. 15   a  and  15   b , in certain embodiments of dressing  10  a plurality of grooves  33  are machined, molded, or cut into skin-facing lower surface  12  of dressing  10 . Grooves  33  are adapted to facilitate the removal of fluids or other exudates from the area under the dressing. As shown in  FIGS. 15   a  and  15   b , grooves  33  are radially extending within lower surface  12  from approximately the center of dressing  10  to the periphery of dressing  10 . The depth of grooves  33  is from about 0.1 mm to about 2 mm, such as 0.2 mm, 0.5 mm, or 1.0 mm. The width of grooves  33  is from about 0.1 mm to about 2 mm, such as 0.2 mm, 0.5 mm, 1.0 mm. 
         [0061]    Referring now to  FIGS. 16   a ,  16   b ,  16   c , and  16   d , in certain embodiments upper surface  14  of dressing  10  has the shape facilitating the application of overdressing  50  (not shown) in the form of adhesive tape or bandage applied over dressing  10 . As shown in  FIGS. 16   a  and  16   b , flat surface areas  33  are cut into body of dressing  10  under angle, so that some horizontal, flat area remains on upper surface  14  adjoined by sloping down flat areas  33 . As shown in  FIGS. 16   c  and  16   d , in one embodiment upper surface  14  is a continuous surface having a shape of a cylinder wall. Advantageously, embodiments shown in  FIGS. 16   a ,  16   b ,  16   c , and  16   d  facilitate uniform application of overdressing such as adhesive tape or bandage without tenting or gaps or air bubbles entrapped under overdressing or between overdressing and upper surface  14  of dressing  10 . 
         [0062]    Embodiments shown in  FIGS. 16   a ,  16   b ,  16   c , and  16   d  have a generally circular or elliptical shape of dressing  10 . In other embodiments (not shown) dressing  10  has a rectangular or specifically square shape, further facilitating uniform application of overdressing over dressing  10 . 
         [0063]    Referring now to  FIG. 17   a , dressing  10  of final shape substantially similar to the embodiments of  FIGS. 1 through 12  is formed of three optionally adhesively joined together subunits, lower disk  500 , middle disk  510 , and upper disk  520 . Lower disk  500  has slit or gap  22  cut radially from about the center of disk  500  to the periphery. Middle disk  510  has channel  20  cut radially from about the center of disk  510  to the periphery. Upper disk  520  forms covering layer of the assembly shown in  FIG. 17   a , with gap  22  aligned with channel  20 .  FIG. 17   b  illustrates the embodiment of  FIG. 17   a  with upper disk  520  removed for better clarity, with gap  22  aligned with channel  20 . 
         [0064]    In one embodiment, all three disks  500 ,  510 , and  520  are made of the same material, and are optionally joined together with an adhesive, preferably with gap  22  aligned with channel  22  as shown in  FIGS. 17   a  and  17   b . In an alternative embodiment, lower disk  500  has skin adhesive disposed on it; middle disk  510  is impregnated with anti-bacterial or anti-septic material; and upper disk  520  has water impermeable properties or water impermeable coating. Advantageously, manufacturing of dressing  10  made of three layers or three disks is simplified, whereby low cost web converting can be used to manufacture three-piece dressing  10 . 
         [0065]    Percutaneous medical devices for which the dressings above can be used include catheters, pins, implants and the like which pass through the skin and are indwelling for some considerable time. Exemplary of percutaneous medical devices are central venous catheters, peripheral venous catheters, Swan-Gaus pulmonary catheters, central nervous system implants (ex. external ventricular drainage and ventricular reservoirs), peritoneal dialysis catheters, such as for continuous ambulatory peritoneal dialysis and continuous cyclic peritoneal dialysis, hemodialysis catheters, transvenous pacemaker leads and temporary orthopedic pins. All of these percutaneous medical devices, when in place, have a portion of the device which is external, that is which is left protruding from the skin, and which can be the cause of infection. 
         [0066]    In a preferred embodiment, dressing  10  is prepared by the steps of cross-linking a polymer which contains chemically reactive functionalities which react with a cross-linking reagent, where the cross-linking agent comprises greater that two reactive sites per molecule which are chemically reactive with functionalities on the biopolymer, to form a cross-linked polymer; optionally, forming the cross-linked biopolymer into a desired shape; then contacting the cross-linked polymer with a bioactive agent to reversibly bind the bioactive agent to the polymer to form the polymeric delivery vehicle. Preferably, the cross-linking reagent is a polyurethane or polyurethane urea having isocyanate side groups and/or end groups. 
         [0067]    Examples of polymers which can be treated with a cross-linking agent according to the present invention include, but are not limited to proteins, peptides and polysaccharides. Preferred polymers are gelatin, collagen, and polysaccharides, particularly cellulose derivatives, as, for example, hydroxyethylcellulose. The thickness of the polymeric matrix may be varied as desired, depending upon the desired pharmaceutical dosage and duration of delivery. Ordinarily, a suitable matrix thickness will be in a range of about 0.1 to 1.0 centimeters. 
         [0068]    The ratio of cross-linking agent to polymer will depend in part on the particular polymer and the bioactive agent with which it is intended to be used. It will be understood that mixtures of different polymers may also be utilized. However, generally, it will be useful to employ a weight ratio of cross-linking agent to biopolymer of from about 20:1 to about 1:1. It will be realized that suitable polymerization initiators may be utilized to initiate the polymerization reaction, which include, but are not limited to azobisisobutylnitrile, peroxide initiators, such as benzoyl peroxide, isopropyl peroxide, and the like. Although polyurethane and polyurethane ureas are the preferred cross-linking agents, other cross-linking agents may be suitable, such as alkylene polyacrylates, alkylene polymethacrylates, alkylene glycolpolymethacrylates, polyalkylene glycolpolymethacrylates, polyaldehydes as well as other cross-linking agents which will cross-link molecules with reactive protic groups. A preferred cross-linking agent is a polyether polyisocyanate that has greater than 2 free isocyanate groups/molecule. 
         [0069]    The top and bottom dressing materials can be formed by molding or casting before cross-linking or, after cross-linking, by cutting. The cross-linked polymer will then be loaded with the desired bioactive agent(s). Typically, the bioactive agent is dissolved in a suitable solvent and then placed in fluid contact with the cross-linked polymer by immersion. The loading of the biopolymer may be readily determined based upon the uptake of the biopolymer of the bioactive agent. 
         [0070]    In a preferred method for forming the loaded cross-linked polymer, the bioactive agent is dissolved in water at a suitable concentration, typically about 1-2% by weight, and the cross-linked biological polymer is immersed therein for a period of about 240 minutes. At ambient temperature (about 20-25° C.), the polymer is then extracted from the solvent, allowed to air dry or is lyophilized, and is then ready for use. 
         [0071]    Alternatively, the cross-linked polymer may be loaded with the bioactive agent, then dried, then cut to a suitable form for use. 
         [0072]    In another preferred method, the bioactive agent and biopolymer are dissolved in an aqueous solvent before cross-linking and the bioactive agent is bound to the polymer. Typical agent: biopolymer weight ratios are in the range of about 1:100 to 5:100 in solution. The polymer is then cross-linked by treatment with the cross-linking agent. 
         [0073]    The invention being thus described, it will be apparent that the same may be varied in many ways. Such variations are not to be regarded as a departure from the spirit and scope of the invention, and all such modifications as would be obvious to one skilled in the art are intended to be included within the scope of the following claims.