Patent Publication Number: US-11027075-B2

Title: Device for percutaneous delivery of therapeutic agents, and a method for its use

Description:
TECHNICAL FIELD 
     Embodiments disclosed herein relate generally to devices for delivery of therapeutic agents into the body, and in particular to devices for percutaneous delivery of therapeutic agents. 
     BACKGROUND ART 
     A number of medical procedures that have recently become more prevalent involve delivering one or more therapeutic agents into the dermis of a user. As distinguished from subcutaneous delivery, which involves injection of agents, such as drugs, beneath the skin, percutaneous delivery requires delivery of agents into or between skin layers. Therapy that uses percutaneous agents is sometimes referred to as mesotherapy (from Greek mesos, “middle” therapeia, “to treat medically”). One therapy using percutaneous delivery that has enjoyed success in recent studies is the stimulation of dermal collagen to alleviate the effects of aging or help make scar tissue more flexible and less disfiguring. Mesotherapy to stimulate collagen production has two components: the use of carefully calibrated physical damage to stimulate collagen production via the healing process, and the delivery of chemical agents into the skin to enhance the stimulatory effect. 
     The first component of the therapy, known as “Microneedling,” is based on the universal concept of healing of skin: when mechanical trauma occurs, skin heals by forming collagen in three stages. The first stage is inflammation. Immediately after trauma, clotting cascade is activated. Platelets secrete inflammatory agents such as cytokines and growth factors that signal fibroblasts in the dermis to produce collagen. The second stage is collagen production. Around the third week following the trauma, collagen production begins. It continues for about 2 weeks and peaks around 6th week after trauma. The third and final stage is collagen remodeling. Collagen is remodeled for the next several months. Results achieved after healing can last for several years. 
     Chemical agents can both assist and complement the microneedling process. Some agents may contribute by providing local nutrients to tissues during the healing process. Other agents may themselves have a further stimulatory effect. In any case, there are multiple studies proving the collagen-stimulating effect of transdermal Vitamins A, C, and E, among other agents. The process of microneedling also provides a convenient way to deliver the chemical agents into the skin of a user. Typically, the desired chemical agent or agents are placed on the surface of the patent&#39;s skin and then pushed into the skin by the needles during the microneedling process. 
     Delivery of therapeutic agents by microneedling is expanding to cover an ever-widening array of treatments in which a diffuse and painless delivery of an agent is preferred. However, the search continues for the most convenient approach for personal home use of these techniques. One approach is to use a dermaroller (or medical needling) in conjunction with creams or serums with vitamins. None of these methods combine the application of the therapeutic agent with the roller in a compact and convenient way suitable for home use. 
     Therefore, there is a need for a device that combines mechanical and chemical collagen stimulation and makes the process easier for the user. 
     SUMMARY OF THE EMBODIMENTS 
     In one aspect, a device for percutaneous delivery of therapeutic agents includes a first wheel having an axis of rotation, a first axial surface rotably mounted on the head, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation of the wheel. The device includes a second wheel having an axis of rotation, a first axial surface affixed to the second axial surface of the first wheel, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation. 
     In a related embodiment, the first axial surface of the second wheel has at least one mortise, and the second axial surface of the first wheel has at least one tenon fitting in the at least one mortise. In an additional embodiment, each of the plurality of needles mounted on the outer surface of the first wheel has a first length and each of the plurality of needles mounted on the outer surface of the second wheel has a second length, the second length differing from the first length. 
     Another embodiment includes a third wheel having an axis of rotation, a first axial surface affixed to the second axial surface of the second wheel, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation. In another embodiment, each of the plurality of needles mounted on the outer surface of the first wheel has a first length, each of the plurality of needles mounted on the outer surface of the second wheel has a second length, and each of the plurality of needles mounted on the outer surface of the third wheel has a third length. In a further embodiment, the first length differs from the second length. In an additional embodiment, the first length differs from the third length. In still another embodiment, the second length differs from the third length. Another embodiment also includes a head, and the second axial surface of the third wheel is rotably mounted on the head. 
     Another embodiment of the device includes a head on which the first wheel and second wheel are rotably mounted. In one embodiment, the first axial surface of the first wheel is rotably mounted on the head. In another embodiment, the second axial surface of the second wheel is rotably mounted on the head. A further embodiment also includes a reservoir mounted on the head, the reservoir containing a fluid, the reservoir having an opening near to the wheel such that the fluid is disposed on the wheel through the opening. 
     In another aspect, a method for manufacturing a device for percutaneous delivery of therapeutic agents includes forming a first wheel having an axis of rotation, a first axial surface, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation of the wheel, forming a second wheel having a first axial surface, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation, and affixing the first axial surface of the second wheel to the second axial surface of the first wheel. 
     A related embodiment, where the first axial surface of the second wheel has at least one mortise, the second axial surface of the first wheel has at least one tenon, affixing the first axial surface of the second wheel to the second axial surface of the first wheel further involves snapping the at least one tenon into the at least one mortise. 
     Other aspects, embodiments and features of the device and method will become apparent from the following detailed description when considered in conjunction with the accompanying figures. The accompanying figures are for schematic purposes and are not intended to be drawn to scale. In the figures, each identical or substantially similar component that is illustrated in various figures is represented by a single numeral or notation. For purposes of clarity, not every component is labeled in every figure. Nor is every component of each embodiment of the device and method shown where illustration is not necessary to allow those of ordinary skill in the art to understand the device and method. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The preceding summary, as well as the following detailed description of the disclosed system and method, will be better understood when read in conjunction with the attached drawings. It should be understood, however, that neither the device nor the method is limited to the precise arrangements and instrumentalities shown. 
         FIG. 1A  is a perspective view of a disclosed device embodying the invention; 
         FIG. 1B  is a side view, partially in section, showing an interior chamber of the disclosed device of  FIG. 1A ; 
         FIG. 2  is a perspective view showing operation of the disclosed device of  FIG. 1 , 
         FIG. 3A  is a perspective view showing another embodiment of the disclosed device; 
         FIG. 3B  is a side view, partially in section, of a portion of the embodiment of the device disclosed in  FIG. 3A ; 
         FIG. 4A  is a side view, of a portion of another embodiment of the device; 
         FIG. 4B  is a side view, in section, of the portion of the embodiment depicted in  FIG. 4A ; 
         FIG. 5A  is view of an embodiment of a mechanism for advancing a plunger in embodiments of the disclosed device; 
         FIG. 5B  is view of an embodiment of a mechanism for advancing a plunger in embodiments of the disclosed device; 
         FIG. 6  is view of an embodiment of a valve in embodiments of the disclosed device; 
         FIG. 7  is a flow chart illustrating one embodiment of the disclosed method; 
         FIG. 8A  is a schematic diagram of an embodiment of the device; 
         FIG. 8B  is a schematic diagram of a wheel as described herein; 
         FIG. 8C  is a schematic diagram of a wheel as described herein; 
         FIG. 8D  is a schematic diagram of a wheel as described herein; 
         FIG. 8E  is a schematic diagram of a wheel as described herein; 
         FIG. 8F  is a schematic diagram of a wheel as described herein; 
         FIG. 9  is a schematic diagram of an embodiment of the device; 
         FIG. 10  is a schematic diagram of an embodiment of the device; 
         FIG. 11  is a schematic diagram of an embodiment of the device; 
         FIG. 12  is a schematic diagram of an embodiment of the device; 
         FIG. 13A  is a schematic diagram of an embodiment of the device; 
         FIG. 13B  is a schematic diagram of an embodiment of the device; and 
         FIG. 14  is a flow chart illustrating one embodiment of the disclosed method. 
     
    
    
     DETAILED DESCRIPTION OF SPECIFIC EMBODIMENTS 
     Embodiments of the disclosed device allow a person to deliver agents percutaneously through microneedle punctures with a single device that may be held and operated with one hand. The disclosed device may also conserve therapeutic agents and avoid messes by delivering the therapeutic agents onto the needles without first applying them to the skin of the user. As a result, the use of embodiments of the disclosed device may be more cost-effective. In some embodiments, placing the fluid directly onto the needles rather than deploying it first on the skin ensures a regular, even coat per needle, creating more predictable results. By not deploying onto the skin, enclosed embodiments avoid difficulties of application that occur when less viscous fluids flow away from the treatment area, or when volatile fluids evaporate. The disclosed embodiments also can administer more viscous fluids than designs involving hollow needles. 
       FIGS. 1A-6  depict embodiments of a device  100  for percutaneous delivery of therapeutic agents. As a brief overview, the device  100  includes a head  101 , a wheel  102  rotably mounted on the head  101 , the wheel  102  having an axis of rotation  103  and an outer surface  104 . A plurality of needles is  105  disposed upon the outer surface  104 , each needle having a tip projecting away from the axis of rotation  103  of the wheel  102 . The device  100  may further include a reservoir  106  mounted on the head  101 . The reservoir  106  may contain a fluid  107 . The reservoir  106  may have an opening  108  near to the wheel  102  such that the fluid  107  is disposed on the wheel  102  through the opening  108 . 
     Referring to  FIGS. 1A-2  in more detail, the device  100  includes a head  101 . The head  101  may be composed of any rigid material or combination of materials that will not react with the therapeutic agents. The head  101  may be composed at least in part of rigid polymers. The head  101  may be composed at least in part of rigid plastic. The head  101  may be composed at least in part of resin. The head  101  may be composed at least in part of wood. The head  101  may be composed at least in part of glass. In some embodiments, the head  101  is composed at least in part of a ceramic material. The head  101  may also be composed at least in part of metal. In some embodiments, the head  101  is composed at least in part of a composite fibrous material such as fiberglass. In some embodiments, the head  101  is hollow; for instance, the head  101  may have a hollow portion that provides a conduit for the fluid  107  to pass from the opening  108  to the wheel  102  as set forth in more detail below. The head  101  may be substantially cylindrical. 
     In some embodiments, the head  101  is detachable from the reservoir  106 . The head  101  may be detachable from the reservoir  106  if the head can be detached and reattached multiple times without damage to the head  101  or reservoir  106 . In some embodiments, as shown in  FIG. 3B , the head is attached to the reservoir via reciprocal threading  133 . In other embodiments, the reservoir  106  has an extension  134  that snaps into a hollow portion of the head  101  as shown in  FIG. 4B . The device  100  may include at least one additional head  101  that may be attached to the reservoir instead of the head  101 ; for instance, the first head  101  may have needles a quarter of a millimeter (0.001 inches) in length for puncturing thin skin, while a second head  101  may have needles a millimeter (0.039 inches) in length for penetrating thicker skin or scar tissue. Some embodiments of the device also include a removable cap  135  that attaches to the head and covers the wheel. 
     In some embodiments, as shown in  FIGS. 5A-B , the head  101  has a hood  110 . The hood  110  may be composed of any materials suitable for the composition of the head  101 . The hood  110  may be composed of the same material as the head. The hood  110  may be composed of a different material from the head. The hood  110  may be permanently attached to the head; for instance, the hood  110  may be fused to the head  101 . The hood  110  may be adhered to the head. The hood  110  and the head  101  may form a single monolithic part. In some embodiments, the hood  110  is so formed that its aperture  111  contacts the skin around substantially all of its rim  112 . The rim  112  of the aperture  111  may be formed of a material that is soft, such as a soft rubber or silicone, to avoid irritating the skin. The rim  112  may be formed of a material that is slick, to enable it to move against the surface of the skin without causing irritation by friction or by pulling on skin hairs. In some embodiments, the hood  110  enables a user who fears or dislikes needles to use the device  100  without having to see the needles; as described below, a cap  135  may engage against the hood such that the user may remove the cap and use the device without ever seeing the needles. As a result, the device  100  may be more generally suitable for home use. The conduit by means of which the fluid  107  passes through the head  101  may open into the hood. 
     The device  100  may include a wheel  102  rotably mounted on the head  101 , the wheel  102  having an axis of rotation  103  and an outer surface  104 . The wheel  102  may be composed of any material or combination of materials suitable for the composition of the head  101 , as set forth above in reference to  FIGS. 1A-2 . The wheel  102  may be journaled on any suitable bearing that allows it to rotate freely about its axis of rotation  103 . The wheel  102  may be mounted on an axle. The wheel  102  may be mounted by means of axle protrusions from its sides that are inserted in pits or holes in the head  101 . In some embodiments, the head has a pair of members  109  that extend from the head  101  to bear the wheel  102  between the members  109 . In other embodiments, the wheel  102  is disposed within the hollow portion of the head  101 , as shown in  FIG. 3A . In some embodiments, the wheel  102  is substantially cylindrical, the axis of rotation  103  is located at the axis of the substantially cylindrical wheel, and the outer surface  104  is the outer curved surface of the substantially cylindrical wheel. The wheel  102  may be detachable from the head  101 . For instance, the head  101  may have bearings for the axle of the wheel that are open on one side, so that the axle can snap into the bearings. The members  109  may be sufficiently flexible to bend apart to allow the axle of the wheel to be inserted into a hole in each member  109 ; the members may be sufficiently rigid to hold the wheel in place once inserted. In some embodiments, the device  100  includes at least one additional wheel that may be attached to the head instead of the wheel. The at least one additional wheel has needles that are a different length from the needles on the wheel  102 ; for instance, the wheel  102  may have needles a quarter of a millimeter (0.001 inches) in length for puncturing thin skin, while an additional wheel may have needles a millimeter (0.039 inches) in length for penetrating thicker skin or scar tissue. 
     Some embodiments of the device  100  include a plurality of needles  105  disposed upon the outer surface  104 , each needle having a tip projecting away from the axis of rotation  103  of the wheel  102 . In some embodiments, the needles  105  are composed at least in part of metal; the metal may be steel. The metal may be titanium. In other embodiments, the needles are composed at least in part of a polymer. The polymer may be a silk derivative such as silk fibroin. The polymer may be silicone. The polymer may be hyaluronic acid. The polymer may be poly-L-lactic acid (PLLA). The polymer may be polylacticoglycolic acid. The polymer may be polylactic acid. The polymer may be polyglycolic acid. The polymer may be polycarbonate. The polymer may be polystyrene. The polymer may be chitosan. The needles may be composed at least in part of a carbohydrate. The carbohydrate may be cellulose. The carbohydrate may be a sugar. The needles may be made of solid or biodegradable polymers that slowly discharge molecules into the skin upon application on the needles. In some embodiments, the needles contain an additional therapeutic substance that diffuses from the needles upon insertion into the skin; for instance, the needles may contain an antibiotic or antiseptic substance to help prevent local infection. The polymer may be insoluble in the skin. In other embodiments, the needles  105  are formed from a substance that dissolves when inserted into the skin of a user; the needles may contain therapeutic agents that are released into the user&#39;s tissues when the needles dissolve. The dissolvable substance may include maltose. The dissolvable substance may include carboxymethylcellulose. The dissolvable substance may include amylopectin. The dissolvable substance may include polymethylvinylether. The dissolvable substance may include polymaleic anhydride. The dissolvable substance may include sodium hyaluronate. The dissolvable substance may include chondroitin sulphate. The dissolvable substance may include chondroitin dextrin. The dissolvable substance may include sodium alginate. The dissolvable substance may include hydroxypropyl cellulose. In some embodiments, the needles are designed to break off in the skin and continue a slow release of therapeutic agents. The needles may be formed of any combination of the above materials. For instance, the needles may be made of metal but then coated with polymers. The wheel and needles may be made of metal but then coated with polymers. The needles may be formed separately from the wheel and then attached. The needles may formed by processing the surface of the wheel; for instance, the needles may be formed by cutting, raising, or otherwise modifying portions of the surface of the wheel. 
     Where the wheel  102  is substantially cylindrical, each of the plurality of needles  105  may extend from the outer surface  104  of the wheel  102  along a radial line through the axis of rotation  103 . Each needle may be perpendicular to the surface of the wheel  104  where the needle joins the surface. In some embodiments, each of the plurality of needles extends from the outer surface by a length of between one quarter of a millimeter (0.001 inches) and one millimeter (0.039 inches). In additional embodiments, each of the plurality of wheels has a diameter of between 20 micrometers (0.00078 inches) and 100 micrometers (0.00394 inches). Each of the plurality of needles may be 70 micrometers (0.0027 inches) in diameter. The plurality of needles  105  includes four to six rows of needles spaced evenly apart on the outer surface  104  of the wheel  102 , in some embodiments; the rows may be parallel circular rows evenly spaced on the outer surface of the wheel  102 , where the wheel  102  is cylindrical. The needles  105  may have any shape conducive to piercing the stratum corneum of the user&#39;s skin. The needles may be substantially cylindrical with a sharpened tip. The needles may have the form of a pyramid. The needles may have the form of an obelisk. The needles may have the form of a substantially flat triangle. In some embodiments, each of the plurality of needles is substantially conical. In some embodiments, each needle has a cross-sectional area at the tip of the needle and a base where the needle joins the outer surface of the wheel, the base having a cross-sectional area at least eight times the cross-sectional area of the tip. The cross-sectional area may reduce from the base to the tip of the needle in any fashion as dictated by the shape of the needle. In some embodiments, the needles have heterogenous forms; for instance, some needles may be conical and others triangular or cylindrical. The base to tip width ratio of the needles may vary as well. 
     The device  100  may further include a reservoir  106  mounted on the head  101 . The reservoir  106  may contain a fluid  107 . The fluid  107  may be any material that behaves like a liquid when subjected to motive pressure as described in further detail below. The fluid  107  may be a liquid. The fluid  107  may be a gel. The fluid  107  may be a cream. The fluid  107  may be a lotion. The fluid  107  may be a viscoelastic substance that can be induced to behave in a fluid-like manner. The fluid  107  may be a non-Newtonian fluid. The fluid  107  may include one or more therapeutic agents; therapeutic agents may be any agents that have a potentially beneficial effect on the health or appearance of the user when applied using the device  100 . The fluid  107  may contain agents including without limitation retinol (vitamin A), ascorbic acid (vitamin C), hyaluronic acid, or peptides. The fluid  107  may include cosmetic agents. The fluid  107  may include pharmaceutical agents. The reservoir  106  may have an opening  108  near to the wheel  102  such that the fluid  107  is disposed on the wheel  102  through the opening  108 . In some embodiments, the reservoir  106  is contained in a tube  113  having a bottom end  114  near to the wheel  102  and a top end  115 , wherein the opening  108  is in the bottom end  114  of the tube. The device  100  may further include a plunger  116  within the tube, and an actuator button  117  set through the top end of the tube and fixed to the plunger  116 , such that depression of the actuator button  117  causes the plunger  116  to force the fluid  107  out through the opening  108 . The space between the plunger  116  and the opening  108  may form the reservoir  106 . The actuator button  117  may be connected to the plunger  116  via a rod  118 ; the rod may have a threaded portion that inserts into a reciprocally threaded cylindrical portion such that rotating the actuator button  117  also moves the plunger  116 , allowing adjustments to ensure that depressing the actuator button  117  will always release a full amount of fluid  107 . The tube  113  may be constructed from any material or combination of materials suitable for constructing the head  101 . 
     In other embodiments, as shown in  FIGS. 5A-B , the device  100  includes a mechanism  119  for automatically advancing the plunger each time the button  117  is depressed.  FIG. 5A  shows one embodiment of the mechanism  119  just after the actuator button (not shown) has been pressed. In this embodiment, the fluid  107  is contained in a tube and pushed toward one end of the tube using a plunger  116 . Continuing the example, the plunger  116  is attached to a threaded rod  120  that is inserted in a reciprocally threaded hollow rod  121 . In this example, the hollow rod  121  is fixed to a cam follower element  122  having a cam follower  123  that rests in a cylindrical cam  124  which revolves once around the interior of the tube. The top and bottom of the cam  124  are connected by a straight channel  125 , in the example. In the example, pressing the button causes the plunger  116  to advance forward, forcing the fluid  107  through the opening, as the cam follower  123  travels down the straight channel. Continuing the example, as shown in  FIG. 5B , upon the return stroke, a biasing means  126 , such as a coiled compression spring, pushes the cam follower element  122  back toward the button, forcing the cam follower  123  to traverse the cylindrical cam  124 , causing the hollow rod  121  to rotate with respect to the rod  120 , which causes the rod  120  to extend further out of the hollow rod  121 ; a wedge cam set  127  may urge the cam follower element  122  toward the straight channel when the button is pressed, and toward the cylindrical cam  124  on the return stroke; alternatively, the cam  124  and straight shaft  125  may have angled portions at their ends that force the cam follower  123  into the cam  124  at the end of the pressing of the button and into the straight shaft  125  at the end of the return stroke. The cam follower  123  may also be shaped to engage the cam  124  during the return stroke and the shaft  125  during the pressing of the button. The threading of the rods  120 ,  121  may be calibrated so that the distance the rod  120  extends out of the hollow rod  121  is equivalent to the distance the plunger advances when the button  117  is pressed. Skilled practitioners in the art will be aware of variations to the above example that accomplish similar results. In other embodiments, the advancement of the plunger is achieved using a ratcheting process. 
     In some embodiments, device includes an airless pump situated to propel fluid through the opening. The airless pump may function by forming a vacuum near the opening  108  that draws fluid  107  through the opening, while allowing air to enter the top end  115  behind a plunger  116  that is drawn forward by the suction created when the fluid  107  is displaced. Persons skilled in the art will be aware of many designs for airless pumps that may be used as a component of the device  100 . In other embodiments, as shown in  FIG. 3A , the reservoir  106  is compressible to force the fluid  107  out through the opening  108 . The reservoir  106  may be composed of a flexible, substantially inelastic material. The reservoir  106  may be composed of flexible plastic. The reservoir  106  may be composed of flexible metal, such as foil. The reservoir  106  may be composed of a flexible organic polymer. The reservoir  106  may be composed of a synthetic polymer. The reservoir  106  may be composed of a natural product such as leather. In some embodiments, the reservoir  106  is composed of a combination of two or more of the above-described materials. For instance, the reservoir  106  may be composed of metal foil and polymer. In some embodiments, the reservoir  106  is composed of a fibrous composite. The above-described methods for expelling fluid  107  from the reservoir  106  enable the device  100  to be used in any orientation without regard to gravity, allowing, for instance, the user to use the device on a vertical or overhanging skin surface. In some embodiments, the opening  108  further includes a nozzle. 
     As shown in  FIG. 6 , the opening  108  may have a valve  128  that stops the opening  108  when the device  100  is not in use; the valve  128  may prevent the fluid  107  from passing through the opening  108  when the device  100  is not in use. In one embodiment, the valve  128  is a slit valve made up of a slit cut in elastic material; the elasticity of the material may exert a recoil force that holds the sides of the slit together so that the force that the fluid  107  exerts on the elastic material under the influence of gravity is insufficient to force the sides of the slit apart. The slit valve may deform during use to permit the fluid  107  to pass through it. The force exerted by the user to eject the fluid  107  from the reservoir  106  is sufficient to force the sides of the slit apart in some embodiments. The valve  128  may be a check valve. For instance, in another embodiment, the valve  128  includes a stopper inserted in the opening  108  from the direction of the head  101 ; the valve  128  in such an embodiment may include a biasing means such as a spring, whose bias urges the stopper into the opening with sufficient force to counteract the force exerted by the fluid  107  on the stopper under the influence of gravity. The bias of the biasing means may be such that the additional force exerted by the user to eject fluid  107  from the reservoir is sufficient to overcome the bias. Alternatively, in embodiments in which the user ejects the fluid  107  by means of an actuator button  117 , the button  117  may also engage a member, such as a rod, that exerts a force on the stopper to push it out of the opening  108 . In other embodiments, the valve  128  includes a stopper  129  inserted in the opening  108  from the direction of the reservoir  106 , such that the force exerted by the fluid  107  on the stopper tends to push the stopper into the opening  108 , sealing the opening  108  against leaks. In some embodiments, pressing the wheel against the user&#39;s skin causes a rod  130  to push the stopper out of the opening  108 , allowing the fluid  107  to flow through the opening  108 . In one embodiment, the head  101  is slideably movable with respect to the reservoir  106 , and is fixedly attached to the rod such that pressure on the head causes the stopper to move out of the opening  108  and into the reservoir; a biasing means  131  such as a coiled compression spring may exert a recoil force urging the head away from the reservoir such that the stopper reinserts in the opening  108  when the pressure against the skin ceases. In another embodiment, the wheel  102  is slidably movable with respect to the head  101 , and the rod is attached to the wheel  102  in a manner permitting the rod to transfer the motion of the wheel to the stopper without interfering with the rotation of the wheel; for instance, the wheel  102  may be journaled on a collar  132  that is fixed to the rod  130 , the collar slideably movable with respect to the head  101 . The collar may be set inside of the head  101  so that only pressure on the wheel  102  itself is likely to disengage the stopper; where there is a cap  135  as set forth below, the cap may cover the wheel and collar such that it is practically impossible to exert pressure on either the wheel or the collar without first removing the cap  135 . The wheel  102  may be attached to the collar by any means by which the wheel is attachable to the head  101 ; the wheel  102  may be detachable from the collar in embodiments in which the wheel  102  may be detached and interchanged with other wheels. Some embodiments of the device also include a removable cap  135  that attaches to the head and covers the wheel. 
       FIG. 7  illustrates some embodiments of a method  700  for percutaneous delivery of therapeutic agents. The method  700  includes providing a device as described above in reference to  FIGS. 1A-5  ( 701 ). The method  700  includes causing the fluid  107  to dispose from the opening  108  onto the wheel  102  ( 702 ). The method  700  includes rolling the wheel  102  firmly against skin of a user, causing the needles  105  to puncture the skin and deliver the fluid  107  into the punctures ( 703 ). 
     Referring to  FIG. 7  in greater detail, and by reference to  FIG. 1A-6 , the method  700  includes providing a device as described above in reference to  FIGS. 1A-6  ( 701 ). The device  100  may be previously assembled by a manufacturer. A user may assemble the device  100 . The user may fill the reservoir  106  with the fluid  107 . Where the head  101  is detachable, the user may attach the head  101  to the reservoir  106 . The user may select the head  101  from a plurality of possible heads  101 ; for instance, where the skin to be treated is thick, the user may select a head  101  having millimeter-long (0.039 inch-long) microneedles instead of a head  101  having half-millimeter-long (0.002 inch-long) microneedles. Where the microneedles are constructed to dissolve upon insertion into skin, the user may select a head that includes microneedles containing the appropriate therapeutic substance. Likewise, where the wheel  102  is detachable from the head and interchangeable with other wheels, the user may select the appropriate wheel for the desired use. If the device  100  includes a cap  135 , the user may remove the cap. 
     The method  700  includes causing the fluid  107  to dispose from the opening  108  onto the wheel  102  ( 702 ). In some embodiments, where the fluid  107  has low viscosity, the user may accomplish this by positioning the head downward, allowing gravity to carry the fluid  107  out the opening. Where there is a valve  128 , the user may activate the valve to allow the fluid to flow; for instance, where the valve is activated by pressure against the wheel  102 , the user may activate the valve upon placing the wheel on the skin. Where the reservoir  106  is contained in a tube  113  with a plunger  116  and actuator button  117 , the user may cause the fluid  107  to dispose from the opening  108  onto the wheel  102  by depressing the actuator button as described above in reference to  FIGS. 1A-2 . Where the reservoir  106  is compressible, the user may cause the fluid  107  to dispose from the opening  108  by compressing the reservoir  106 . 
     The method  700  includes rolling the wheel  102  firmly against skin of a user, causing the needles  105  to puncture the skin and deliver the fluid  107  into the punctures ( 703 ). The user may repeat the steps of causing the fluid  107  to dispose on the wheel  102  and rolling the wheel  102  on the skin one or more times, as needed to cover the region to be treated. 
       FIGS. 8A-F  depict embodiments of a device  800  for percutaneous delivery of therapeutic agents. As a brief overview, the device  800  includes a first wheel  801 . The first wheel  801  has a first axial surface  802 . The first wheel  801  has a second axial surface  803 . The first wheel  801  has an outer surface  804 . The first wheel  801  includes plurality of needles  805  disposed upon the outer surface  804 , each needle having a tip projecting away from the axis of rotation of the wheel. The device  800  includes a second wheel  806  having a first axial surface  807  affixed to the second axial surface  803  of the first wheel  801 . The second wheel  806  has a second axial surface  808 . The second wheel  806  has an outer surface  809 , and a plurality of needles  810  disposed upon the outer surface  809 , each needle having a tip projecting away from the axis of rotation. 
     Viewing  FIGS. 8A-E  in further detail, the device  800  includes a first wheel  801 . The first wheel  801  may be composed of any material or combination of materials suitable for the construction of the wheel  102  described above. The first wheel  801  may have any suitable shape for a wheel; for instance, the first wheel  801  may be substantially cylindrical, toroidal, or a shape combining cylindrical and toroidal attributes, such as a cylinder with a rounded outer surface  804 . In some embodiments, the outer surface  804  of the first wheel  801  is the surface that contacts a surface over which the first wheel  801  rolls; in other words, the outer surface  804  may serve the role of a rim, tread, or tire in a typical wheel. The plurality of needles  805  may be disposed on the outer surface  804  in any configuration suitable for the plurality of needles  105  described above. In some embodiments, the plurality of needles  805  is disposed in a substantially radially symmetrical array. The needles may be arranged in a single file forming a circle located halfway between the first axial surface  802  and the second axial surface  803  of the first wheel  801 . Each of the plurality of needles  805  may have any form suitable for any of the plurality of needles  105  described above. Each of the plurality of needles  805  may be formed from any material or combination of materials suitable for forming the plurality of needles  105  described above. 
     The first wheel has a first axial surface  802 . In some embodiments, the first axial surface  802  is substantially flat. In other embodiments, the first axial surface is curved or faceted. The first axial surface  802  may have any features that are suitable for the first axial surface  807  of the second wheel  806  as described in further detail below. The first axial surface  802  may have features that complement the features of the first axial surface  807  of the second wheel  806  as described in further detail below. The second axial surface  803  may have any form suitable for the first axial surface  802 . In some embodiments, the second axial surface has substantially the same form as the second axial surface  808  of the second wheel  806 , as described in further detail below. 
     The device  800  includes a second wheel  806  having a first axial surface  807  affixed to the second axial surface  803  of the first wheel  801 . The second wheel  806  has a second axial surface  808 . The second wheel  806  has an outer surface  809 , and a plurality of needles  810  disposed upon the outer surface  809 , each needle having a tip projecting away from the axis of rotation. The second wheel  806  may be made of any material or combination of materials suitable for the construction of the first wheel  801 . The second wheel  806  may have any form suitable for the form of the first wheel  801 . 
     The first axial surface  807  of the second wheel  806  is affixed to the second axial surface  803  of the first wheel  801 . The two surfaces may be affixed together by any means, including adhesion, fastening with fasteners such as screws, rivets, or staples, attachment using heat such as soldering, welding, brazing, fusion bonding, or other means. In some embodiments, the first axial surface  807  of the second wheel  806  and the second axial surface  803  of the first wheel  801  have complementary features that affix the two surfaces together. For instance, in one embodiment, the first axial surface  807  of the second wheel  806  has at least one mortise  811 , and second axial surface  803  of the first wheel  801  has at least one tenon  812  fitting in the at least one mortise  811 . The at least one mortise  811  may be any depression in the first axial surface  807  of the second wheel  806 , such as a cavity, hole, groove, slot, pit, or other feature, into which a projecting member on another object may be inserted. The at least one mortise  811  may have any shape; for instance, the mortise  811  may include a cylindrical or rectangular hole or pit, or a pit having any regular or irregular polygonal or curved cross-sectional form, as well as cross-sectional forms combining polygonal or curved elements. Likewise, the at least one mortise  811  may have any other form usable for a groove or other depression into which a projecting member may be fitted. The at least one tenon  812  may include a projecting member on the second axial surface  803  of the first wheel  801  that fits in the at least one mortice  811  to form a close and secure joint; the joint may be close and secure if the at least one tenon  812  exerts enough friction force on the at least one mortise  811 , when inserted, to hold the second axial surface  803  of the first wheel  801  firmly against the first axial surface  807  of the second wheel. The shape of the at least one tenon  812  may be substantially the same as the shape of the mortise  811 ; for instance, the at least one mortise  811  may include a cylindrical cavity and the at least one tenon  812  may include a cylindrical projection having very slightly smaller dimensions than the at least one mortice  811 , so that the at least one tenon  812  fits snugly within the at least one mortise  811 . The at least one tenon  812  may have a shape that differs from the shape of the at least one mortise  811  while still fitting snugly within the at least one mortise  811 ; for instance, the mortise  811  may have a cylindrical shape and the tenon  812  may have a star-shaped or polygonal cross section, the vertices of which contact the side of the cylinder. 
     In some embodiments, there are two mortises in the second axial surface  803  of the first wheel  801  and there are two tenons on the first axial surface  807  of the second wheel  806 . In other embodiments, at least one mortise is on the second axial surface  803  of the first wheel  801 , and at least one tenon is on the second axial surface  803  of the first wheel  801 , while a corresponding at least one tenon and at least one mortise may be found on the first axial surface  807  of the second wheel  806 . As persons skilled in the art will be aware, the at least one mortise and at least one tenon may include more than two mortise and tenon combinations. The first wheel  801  and second wheel  806  may be joined by inserting the at least one tenon  812  into the at least one mortise  812 , for instance as illustrated in  FIG. 9 . 
     In some embodiments, one or more features of the first wheel  801  are substantially identical to corresponding features of the second wheel  806 . For instance, the first axial surface  802  of the first wheel  801  may be substantially the same as the first axial surface  807  of the second wheel  806 . Likewise, the second axial surface  803  of the first wheel  801  may be substantially identical to the second axial surface  808  of the second wheel  806 , or the outer surface  804  of the first wheel  801  may be substantially identical to the outer surface  809  of the second wheel  806 . In some embodiments, the first wheel  801  is substantially identical to the second wheel  806 ; the first wheel  801  and second wheel  806  may be made using the same manufacturing process, for instance, in a plurality of substantially identical wheels are produced, and the first wheel  801  and second wheel  806  are two wheels of the plurality of substantially identical wheels. 
     In some embodiments, as illustrated for instance in  FIG. 10 , each of the plurality of needles  805  mounted on the outer surface  804  of the first wheel  801  has a first length and each of the plurality of needles  810  mounted on the outer surface  809  of the second wheel  806  has a second length, the second length differing from the first length. The first length may be greater than the second length, or less than the second length. In some embodiments, this allows for the simple manufacturing process of a mesotherapy device having needles of varying lengths. 
     In some embodiments, as illustrated for example in  FIG. 11 , the device also includes a third wheel  1101  having an axis of rotation, a first axial surface  1102  affixed to the second axial surface of the second wheel  806 , a second axial surface  1103 , an outer surface  1104 , and a plurality of needles  1105  disposed upon the outer surface  1104 , each needle having a tip projecting away from the axis of rotation. The third wheel  1101  may have any form suitable for use as the first wheel  801  as described above. The third wheel  1101  may be constructed of any material or combination of materials suitable for the construction of the first wheel  801  as described above. The first axial surface  1102  of the third wheel  1101  may be attached to the second axial surface  808  of the second wheel  806  in any manner as described above, including joining using mortises and tenons. One or more features of the third wheel  1101  may be substantially identical to one or more features of the first wheel  801  or second wheel  806  as described above. The third wheel  1101  may be substantially identical to the first wheel  801  or the second wheel  806  as described above. 
     In some embodiments, each of the plurality of needles  805  mounted on the outer surface  804  of the first wheel  801  has a first length, each of the plurality of needles  810  mounted on the outer surface  809  of the second wheel  806  has a second length, and each of the plurality of needles  1105  mounted on the outer surface  1104  of the third wheel  1101  has a third length. As illustrated for example in  FIG. 12 , in some embodiments, the first length differs from the second length. In other embodiments, the first length differs from the third length. The second length may differ from the third length. As before, this enables the rapid manufacturing of a mesotherapy device having needles of up to three distinct lengths. In place of differing lengths, the needles may have different forms in other ways; for instance, the needles on the first wheel may have a different shape, thickness, or composition from the needles on the second wheel, which may have a different shape, thickness, or composition from the needles on the third wheel. Any manner of varying the needles as described above in reference to  FIGS. 1A-6  may be used to vary the needles from one wheel to another wheel. Likewise, additional wheels (e.g., a fourth wheel, a fifth wheel, and so on) may be attached to the first, second, and third wheels. 
     In some embodiments, as illustrated for example in  FIGS. 13A-B , the mesotherapy device  800  has a head  1300 . The head  1300  may be formed in any manner described above in reference to  FIGS. 1A-6 . The combined first wheel  801  and second wheel  806  may be journaled on the head in any manner disclosed above in reference to  FIGS. 1A-6 . For example, the third wheel may be rotably mounted on the head; the second or first axial surface of the third wheel may be rotably mounted on the head. Likewise, the first wheel may be rotably mounted on the head; the second or first axial surface of the first wheel may be rotably mounted on the head. Similarly, the second wheel may be rotably mounted on the head; the second or first axial surface of the second wheel may be rotably mounted on the head. 
     In some embodiments, as shown for instance in  FIGS. 8A-F  and  13 B, the first wheel  801  and second wheel  806  have a central cavity  813 ; the central cavity  813  may be a hole through the first wheel  801  or second wheel  806  at the axis, or a pit in the first  802 ,  807  or second  803 ,  808  axial surfaces. In some embodiments, the central cavity  813  is radially symmetrical about the axis of rotation. The central cavity  813  may be circular; in other words, a cross-section taken of the central cavity in a plane perpendicular to the axis of rotation may have a circular perimeter. The central cavity  813  may be substantially cylindrical. In some embodiments, the head  1300  has at least one projection  1301  that fits in the central cavity  813 . In some embodiments, a first projection  1301  on one side of the head fits into a central cavity  813  of the first wheel  801 , and a second projection  1301  on the other side of the head  1300  fits into a central cavity  813  of another wheel, such as the second wheel or the third wheel. 
     The device  800  may include a reservoir mounted on the head, the reservoir containing a fluid, the reservoir having an opening near to the wheel such that the fluid is disposed on the wheel through the opening. This may be implemented as described above in reference to  FIGS. 1A-6 . 
       FIG. 14  illustrates some embodiments of a method  1400  for manufacturing a device for percutaneous delivery of therapeutic agents. The method  1400  includes forming a first wheel having an axis of rotation, a first axial surface, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation of the wheel ( 1401 ). The method  1400  includes forming a second wheel having a first axial surface, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation ( 1402 ). The method  1400  includes affixing the first axial surface of the second wheel to the second axial surface of the first wheel ( 1403 ). 
     Referring to  FIG. 14  in greater detail, and by reference to  FIGS. 8A-13B , the method  1400  includes forming a first wheel having an axis of rotation, a first axial surface, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation of the wheel ( 1401 ). The first wheel  801  may be formed by any process suitable for forming a rigid component, including but not limited to molding methods such as injection molding, extrusion, casting, stamping, rapid prototyping processes such as three-dimensional printing, thermoforming, machining, or any other fabrication methods. The first wheel  801  may be produced as a monolithic unit or by joining two or more pieces together to form the first wheel  801 . 
     The method  1400  includes forming a second wheel having a first axial surface, a second axial surface, an outer surface, and a plurality of needles disposed upon the outer surface, each needle having a tip projecting away from the axis of rotation ( 1402 ). This may be implemented as described above for forming the first wheel  801 . 
     The method  1400  includes affixing the first axial surface of the second wheel to the second axial surface of the first wheel ( 1403 ). This may be implemented as described above in reference to  FIGS. 8A-13B . In some embodiments, where the first axial surface  807  of the second wheel  806  has at least one mortise  811 , and the second axial surface  803  of the first wheel  801  has at least one tenon  812 , affixing the second axial surface  803  of the first wheel  801  to the first axial surface  807  of the second wheel  806  further involves inserting or snapping the at least one tenon  812  into the at least one mortise  811 . 
     It will be understood that the system and method may be embodied in other specific forms without departing from the spirit or central characteristics thereof. The present examples and embodiments, therefore, are to be considered in all respects as illustrative and not restrictive, and the device and method is not to be limited to the details given herein.