Drug delivery devices

A drug delivery device for delivering a drug to a preselected treatment site, includes a rupturable film capsule enclosing a quantity of the drug to be delivered; an array of micro-needles formed with passageways therethrough carried by the device; a covering layer overlying the capsule and forming a fluid-tight seal with the perimeter of the micro-needle array such that when the device is located with the micro-needles facing the treatment site, the application of pressure to the device causes the micro-needles to penetrate the treatment site and the capsule film to rupture to deliver the drug via the passageways to the treatment site; and an open mesh layer adjacent to the array of micro-needles effective, upon rupture of the capsule film, to uniformly distribute the drug to the micro-needles and also to reduce the possibility of clogging of the passageways.

FIELD AND BACKGROUND OF THE PRESENT INVENTION

The present invention relates to drug delivery devices, and particularly to such devices which deliver the drug via micro-needles and/or iontophoretically.

The conventional way of transdermal drug delivery, namely by hypodermic syringe injection, is very unpleasant and painful, and therefore many alternative ways of drug delivery have been developed. The transdermal patch delivers the drug by diffusion, utilizing merely a concentration gradient as a driving force, but this technique is not very effective with respect to large-molecule drugs, such as proteins and peptides, or drugs which otherwise do not have the proper physiochemical properties for diffusion through the skin.

In recent years, micro-needle type drug delivery devices have been developed for increasing the permeability of the skin by micro-needles having a length of up to about 150 microns, sufficiently short so as not to engage the nerve endings but long enough to penetrate the cornified outer body surface layer. They can be produced from a variety of materials, such as silicon, metal and plastic polymers, in many different sizes and shapes. Examples of such micro-needle type drug delivery devices are described in U.S. Pat. Nos. 3,964,482, 6,611,707, 6,656,147 and 6,558,361, the contents of which are incorporated herein by reference.

An object of the present invention is to provide a drug delivery device of the micro-needle type having a number of advantages, as will be described more particularly below.

BRIEF SUMMARY OF THE PRESENT INVENTION

According to one aspect of the present invention, there is provided a drug delivery device for delivering a drug to a preselected treatment site, comprising: a capsule having a rupturable film enclosing a quantity of the drug to be delivered; an array of micro-needles mounted on a supporting matrix carried by the device, the micro-needles being formed with inlet ends facing the capsule, outlet ends to face the treatment site when the device is located with the micro-needles facing the treatment site, and passageways connecting the inlet and outlet ends, whereby the application of pressure to the device causes the outlet ends of the micro-needles to penetrate the treatment site, the capsule film to rupture, and the inlet ends of the micro-needle to deliver the drug via the passageways to the treatment site; and a porous mesh layer between the capsule and the complete surface of the inlet ends of the micro-needles effective to space the inlet ends of the micro-needles from the capsule, to uniformly distribute the drug to the inlet ends of the micro-needles by a wick action, and, upon the rupture of the capsule film, to reduce the possibility of clogging of the passageways as the drug is delivered therethrough from the capsule to the treatment site.

A number of preferred embodiments of the invention are described below for purposes of example. In most of the described preferred embodiments, the device further comprises an outer deformable fluid-tight layer overlying the capsule and having an outer peripheral edge hermetically secured to the outer peripheral edge of the array of micro-needles so as to enclose the capsule between the array of micro-needles and deformable fluid-tight layer, the deformable fluid-tight outer layer being deformable by pressure to permit rupturing the capsule by the application of pressure thereto.

According to another aspect of the present invention, there is provided a drug delivery device for delivering a drug to a preselected treatment site, comprising:

a rupturable film capsule enclosing a quantity of the drug to be delivered;

an array of micro-needles formed with passageways therethrough mounted on a supporting matrix carried by the device such that when the device is located with the micro-needles facing the treatment site, the application of pressure to the device causes the microneedles to penetrate the treatment site and the capsule film to rupture to deliver the drug via the passageways to the treatment site; and a housing open at one end and configured to be applied to opposing sides of a body part, including the treatment site, with the array of micro-needles facing tissue at the treatment site to which the drug is to be delivered, and further comprising an outer sleeve telescopically receiving the housing and configured with respect to the housing such that axially displacing the outer sleeve towards the housing open end causes opposing sides of the splayed housing to converge and the array of micro-needles to penetrate tissue at the treatment site, and the capsule to rupture to deliver the drug to the underlying tissue.

According to yet another aspect of the present invention, there is provided a drug delivery device for delivering a drug to a treatment site comprising a housing carrying the rupturable film capsule enclosing a quantity of the drug to be delivered, an array of micro-needles formed with passageways therethrough mounted on a supporting matrix carried by the device such that when the device is located with the micro-needles facing the treatment site, the application of pressure to the device causes the micro-needles to penetrate the treatment site and the capsule film to rupture to deliver the drug via the passageways to the treatment site, and an outer deformable fluid-tight layer hermetically secured to the outer peripheral edge of the array of micro-needles so as to enclose the capsule between the array of micro-needles and deformable fluid-tight layer, the deformable fluid-tight outer layer being deformable by pressure to permit rupturing the capsule by the application of pressure thereto; the housing being open at one end and being of a generally splayed configuration and configured to be applied to opposing sides of a tooth, with an array of micro-needles facing tissue at the treatment site or sites to which the drug is to be delivered, and further comprising an outer sleeve telescopically receiving the housing and configured with respect to the housing such that axially displacing the outer sleeve towards the housing open end causes opposing sides of the splayed housing to converge and the array of micro-needles to penetrate tissue at the treatment site, and the capsule to rupture to deliver the drug to the underlying tissue.

According to a further aspect of the present invention, there is provided a drug delivery device configured for delivering a drug to a preselected treatment site within a body lumen, comprising; a rupturable film capsule enclosing a quantity of the drug to be delivered; an array of micro-needles formed with passageways therethrough carried by the device such that when the device is located with the micro-needles facing the treatment site, the application of pressure to the device causes the micro-needles to penetrate the treatment site and the capsule film to rupture to deliver the drug via the passageways to the treatment site; and a balloon which is inflatable at the treatment site to produce the pressure to cause the array of micro-needles to penetrate the treatment site and the capsule to rupture.

According to yet another aspect of the present invention, there is provided a drug delivery device for delivering a drug to a preselected treatment site, comprising a rupturable film capsule enclosing a quantity of the drug to be delivered; an array of micro-needles formed with passageways therethrough mounted on a supporting matrix carried by the device such that when the device is located with the micro-needles facing the treatment site, the application of pressure to the device causes the micro-needles to penetrate the treatment site and the capsule film to rupture to deliver the drug via the passageways to the treatment site; a peelable protective layer covering the micro-needles; and a layer of a hydrogel over and between the micro-needles and covered by the peelable protective layer.

According to yet another aspect of the invention, there is a provided a drug delivery device for delivering a drug to a preselected treatment site, comprising at least one body of a hydrogel wherein the drug to be delivered is held in solution form within the hydrogel such that the drug may be iontophoretically driven into the treatment site.

Further features and advantages of the invention will be apparent from the description below.

It is to be understood that the foregoing drawings, and the description below, are provided primarily for purposes of facilitating understanding the conceptual aspects of the invention and possible embodiments thereof, including what is presently considered to be a preferred embodiment. In the interest of clarity and brevity, no attempt is made to provide more details than necessary to enable one skilled in the art, using routine skill and design, to understand and practice the described invention. It is to be further understood that the embodiments described are for purposes of example only, and that the invention is capable of being embodied in other forms and applications than described herein.

DESCRIPTION OF PREFERRED EMBODIMENTS

FIG. 1schematically illustrates one form of drug delivery device constructed in accordance with the present invention for delivering a drug to a preselected treatment site. The illustrated device, generally designated10, includes a capsule11containing a quantity of the drug11aenclosed within a rupturable film11b. The illustrated device further includes an array12of hollow micro-needles12aformed with passageways12btherethrough and micro-needle supporting fluid-tight matrix12c. As will be described in greater detail below particularly with respect toFIGS. 2a-2c, it is particularly advantageous if the micro-needle array supporting matrix12cis of a flexible nature. Array12is located on one side of capsule11, and an outer deformable, fluid-tight layer13overlies the opposite side of the capsule. The outer deformable layer13has an outer peripheral edge secured to the outer peripheral edge of the micro-needle array12in any suitable manner to ensure a fluid-tightness, e.g. by forming the outer layer13with a peripheral bead13areceived within a peripheral recess12dformed in the micro-needle array12.

As will be described more particularly below, the illustrated device is to be located with the micro-needles12aof array12facing the treatment site, such that the application of pressure to the outer layer13causes the micro-needles to penetrate the treatment site, and the capsule film11bto rupture, whereby the drug is delivered via passageways12bto the treatment site.

Although the outer deformable fluid-tight layer13may be composed of a wide variety of materials, it is particularly advantageous for it to be composed of an elastic material such as latex or chloroprene or butyl rubber, which is also preferably pre-tensioned. The significant advantage of having a pretensioned highly elastic cover layer is that the stored energy contained within the layer will contribute to the emptying of the rupturable capsule11following its initial rupture, even in the absence of any other externally applied force tending to empty the capsule. Furthermore, because outer layer13is attached to the perimeter of the micro-needle array substrate layer, which during application to the patient is functionally in contiguity with the underlying body surface, outer layer13, in its natural fully collapsed state, tends to closely conform to the upper surface of the micro-needle array substrate layer, thus tending to empty the capsule to the greatest extent possible.

The illustrated drug delivery device further includes a porous mesh layer14between the capsule11and the micro-needle array12. Porous mesh layer14may be of any biocompatible natural or synthetic fibers14a(FIG. 3), which for example, may be woven in an open mesh to define spaces14bbetween the fibers, or may consist of an unstructured or non-woven mesh, e.g., of cotton or Dacron fibers. Layer14is effective, after the capsule film11bhas been ruptured, to uniformly distribute the drug, by a wick action, over the inner surface of the micro-needles12afor delivery to the treatment site via the passageways12b. Porous layer14is configured so as to not impede the flow of the drug. It is also effective to reduce the possibility of clogging the passageways12bby the ruptured capsule film11bsince it tends to space the film away from the inlet ends of the passageways. That is to say, the porous mesh layer14is located between the capsule and the surface of the inlet ends of the micro-needles and is effective to space the inlet ends of the micro-needles from the capsule, to uniformly distribute the drug to the inlet ends of the micro-needles, and, upon rupture of the capsule film, to reduce the possibility of clogging of the passageways as the drug is delivered therethrough from the capsule to the treatment site.

A further use to which the porous layer14may be put is that it may incorporate protrusions14con its surface facing the capsule, as shown inFIG. 4a, which may be useful in determining the site of rupture of the capsule wall11b. A further modification would be to provide an open celled porous sponge layer14d, which overlies the mesh layer and in its expanded state tends to prevent the protrusions14cfrom directly contacting the underside of the rupturable capsule11, is shown inFIG. 4b.FIG. 4cis a side view of the mesh14a, protrusions14cand sponge layer14d, and serves to illustrate the spatial arrangement of these components.

An alternative to having protrusions14cwould be to have double sided micro-needles as shown at14einFIG. 4d, in place of the single sided micro-needles illustrated in the accompanying figures, such that the portion of the micro-needle extending inward toward the drug containing capsule would replace elements14c. In this case, the micro-needles would serve the dual purposes of breaching the patient's body surface and of puncturing the drug containing capsule with the added advantage of forming a direct link between the source of the drug material and the tissue site.

The drug delivery device illustrated inFIG. 1further includes a peelable protective layer15covering the micro-needles12a, and a layer of an adhesive material such as a hydrogel layer16over the micro-needles12a. Hydrogel layer16partially fills the space between the micro-needles and the peelable protective layer15.

Preferably, hydrogel16includes adhesive and also antiseptic as well as topical anesthetic properties. As will be described more particularly below with respect toFIG. 5, the construction is such that after the delivery device has been applied to deliver the drug to the treatment site, the device may be removed from the treatment site, and at least a portion of the hydrogel layer16will remain on and cover the treatment site. As mentioned, hydrogel layer16can also include an anesthetic material which may be of particular benefit in certain applications, e.g. when the device is used for treating a region of a tooth's supporting soft tissues and in particular the supporting soft tissues surrounding the tooth's roots as described below. It may also include an electrically conductive material to facilitate the drug's movement into the treatment site by iontophoresis or electroporation.

As alluded to above with respect to micro-needle array supporting matrix12c, an important feature is derived from the combined use of a flexible substrate of the micro-needle array together with the adhesive layer which is preferably a hydrogel layer. This can provide an enhanced ability to align the micro-needles perpendicular to the underlying tissues when the tissues have a non-planar topography, as is depicted inFIGS. 2aand2b. This is of particular importance in the case of the soft tissues surrounding the teeth, that is the oral mucosal and gingivae, which tend to be stiff and unyielding and have a complex non-planar topography.

In the case where the micro-needle supporting matrix is inherently inflexible, it may nevertheless still be possible to obtain the desired degree of flexibility of the micro-needle array by mounting small clusters of the micro-needles onto a flexible membrane while making sure that the flexible membrane surface does not occlude the micro-needle passage ways.

Another important benefit in the combined use of the hydrogel and flexible substrate is that the highly flexible and highly adhesive hydrogel layer readily adapts itself to the contours of the tissues and tightly adheres to them. Since the bases of the individual micro-needles are embedded in the hydrogel, the micro-needles would be also be aligned perpendicularly to the tissues if the substrate of the micro-needle array is sufficiently flexible to allow for this. When force is brought to bear on the device, the properly aligned micro-needles will thus penetrate beyond the cornified tissue layer of the body surface in an effective manner. As can be seen inFIG. 2c, when the microneedle array penetrates the outer tissue surface following the application of pressure, the hydrogel layer remains attached to the tissue surface and ultimately the free side of the hydrogel comes into adhesive contact with the matrix of the micro needle array. This ensures the effective coupling of the microneedle array supporting matrix to the tissue surface.

As described previously, after the cornified body surface layer has initially been impaled by the micro-needles12, and after the capsule11has been subsequently ruptured, the continued application of force to the device will cause the fluid contents to flow through the micro-needles into the tissues.

In the case where the outer layer13is composed of a pretensioned elastic material, and the device is adhesively attached to the body surface using for example a hydrogel layer, it may be unnecessary for there to be a continued force brought to bear on the device to continue and ultimately complete the injection process, since the stored energy of the outer layer13will tend to drive the liquid contents out of the capsule while the adhesive attachment of the device to the body surface will tend to maintain an adequate coupling of the device to the body surface.

In this way, the remainder of the injection process, after the actual initiation of the process of impaling the surface and rupturing the capsule has been achieved, will proceed in a self sustained manner, that is, without the need for the operator to continue to press the device on the patient.

In situations in which the device is applied to a body region which has a complex, or otherwise non-planar topography, the effective emptying of the capsule will be aided by the addition of a closed cell, non-absorbent sponge like material, shown inFIG. 2bat17. This is interposed between the outer cover layer13and the upper surface of the rupturable capsule11, and is capable of conforming to the shape of the residual volume throughout the capsule emptying process. A compliant fluid filled bag could also used in lieu of the sponge like material to achieve the same effect.

FIG. 5schematically illustrates various stages in the application of the drug delivery device10to a treatment site TS. Thus, after the protective layer is removed from pressure-sensitive adhesive16aon the outer surface of the device opposite to the micro-needle side as shown atFIG. 5(a), the device is adhesively attached to the operator's finger as shown atFIG. 5(b). Subsequently, protective layer15is removed from hydrogel layer16covering the micro-needle array12, and device10is placed on the treatment site TS with micro-needles12ain contact with the treatment site, as shown atFIG. 5(c); finger pressure is then applied, as shown atFIG. 5(c), to cause the micro-needles12ato penetrate the treatment site and the capsule film11bto rupture, thereby forcing the drug11awithin the capsule through the passageways12bof the micro-needle array, as shown atFIG. 5(c); and then the device is removed from the treatment site, to thereby leave the hydrogel layer16covering the treatment site, as shown atFIG. 5(d). The last step, shown atFIG. 5(d), may be effected by merely finger-grasping the device and removing it from the treatment site; or as illustrated in this case, the pressure-sensitive adhesive on the outer surface of the device permits removal of the device from the treatment site by adhesion with the user's finger.

Initial attachment of the device to the operators finger using the pressure-sensitive adhesive prior to its application to the treatment site, may facilitate accurate placement of the device and promote stable operator pressure application during the injection process.

As described above, the provision of the porous layer14between the capsule11and the micro-needle array12better assures that upon rupture of the capsule film11b, the drug11awithin the capsule will be uniformly distributed over the inner surface of the micro-needle array12for transfer via passageway12bto the treatment site. The provision of mesh layer14also reduces the possibility of clogging of the passageways12bby the capsule film11bwhen the film is ruptured.

As also described above, the provision of the hydrogel layer16, which is preferably retained over the treatment site as shown atFIG. 5(d), not only provides antiseptic protection and possibly anesthetic conditioning to the treatment site, but also covers the treatment site to block any outflow of the drug delivered to the treatment site.

FIG. 6illustrates a variation in the construction of the drug delivery device10, in that the outer flexible layer13of the device is fixed to, or is integrally formed with, a finger sleeve20receivable over the user's finger to facilitate the application of the device to the treatment site, and its removal from the treatment site. The device illustrated inFIG. 6is otherwise of the same construction and may be used in the same manner as described above with respect toFIGS. 1-5.

FIG. 7illustrates another construction of drug delivery device in accordance with the present invention and the manner of using it for delivering the drug to a treatment site. The device illustrated inFIG. 7, as shown at (a), also includes a drug capsule31, a micro-needle array32, an outer deformable layer33, and an open mesh layer34between the capsule and the micro-needle array32. In this particular case, the capsule31has a height substantially larger than its length and width, however the relative dimensions may be varied. In addition, the outer deformable layer33, instead of being of a pliable plastic material as described above, is of a bellows construction to permit it to be deformed in order to rupture the capsule for delivering the drug therein to the treatment site via the micro-needles of the micro-needle array32. To facilitate the deformation of the outer layer33, it preferably carries, or is integrally formed with, a rigid or semi-rigid (stiff) center disc36for convenient engagement by the user's finger to apply the pressure which causes the micro-needles to penetrate the treatment site, and also the drug capsule to rupture and thereafter causes the liquid contents of the capsule to continue to be impelled into the tissue The space between capsule31and the outer bellows layer33may be filled with sponge rubber or other compressible filler material37.

As shown inFIG. 7b, drug delivery device30may further include an adhesive tape38, with or without a semi rigid covering surface, applied over the center disc36of the device. Adhesive tape38with or without a semi rigid covering surface includes lateral extension38aon its opposite sides coated with a pressure-sensitive adhesive38bso as to retain the device over the treatment site TS after applied thereto, as shown inFIG. 7c. A body of compressible sponge, or an expansion spring may also be placed between the center disk36and the underside of adhesive tape38, with or without a semi rigid covering surface. The benefit of this addition is that following the micro-needle's penetration of the treatment site and the drug containing capsule's rupture during the initial application process, and following subsequent adhesion to the body surface, the compressed sponge or expansion spring would further contribute to the continuing provision of a predetermined, and substantially constant driving force for causing the liquid contents of the capsule to continue to be impelled into the tissue.

The above described arrangement may also be used in conjunction with the types of drug delivery devices described above.FIG. 7dshows the manner in which this may be applied. A semi rigid covering surface which includes lateral extension38aon its opposite sides coated with a pressure-sensitive adhesive38b, overlying a rigid or semi-rigid (stiff) central disc36which is in turn attached to a compressible sponge or expansion spring39, optionally with a further disk36at its opposite end. This is in turn applied to any of the units of the type described inFIGS. 1 and 2for the purpose of providing an ongoing driving force for causing the liquid contents of the capsule to continue to be impelled into the tissue after the micro-needles have initially penetrated the treatment site, and the drug capsule has been ruptured and adhesive surface38bis attached to the tissue surface, as mentioned above. Following adhesion to the body surface, the compressed sponge or expansion spring39provides a continuous predetermined and substantially constant driving force for causing the liquid contents of the capsule to continue to be impelled into the tissue.

FIG. 8illustrates another construction of a drug delivery device for delivering a drug, such as an anesthetic or antibiotic, to the gingival tissue and/or oral mucosal tissues of a patient's mouth during a dental treatment, and also several phases in such a dental treatment. The construction illustrated inFIG. 8, and therein generally designated40, includes a housing41, open at the upper end, and lined on its inner surface with by an elastic sponge like material45. Housing41is of a generally splayed configuration and is configured to be applied to opposing sides of the tooth (or other body part) with the array of micro-needles facing tissue at the treatment site to which the drug is to be delivered. A drug delivery device10a,10b, corresponding to device10inFIG. 1, is carried on the inner surfaces of the opposing walls of the housing with the micro-needle array12of each device facing inwardly so as to be engageable with gingival/oral mucosal tissue on the opposite sides of the tooth being treated. For example, the outer deformable layer13of each drug delivery device10may be secured in any suitable manner to, or integrally formed with, the sponge layer45lining the inner surface of housing41, preferably in a manner allowing each device10to pivot in order to accommodate itself to the gingival surface to be engaged by its micro-needle array12.

The assembly40illustrated inFIG. 8further includes an outer sleeve42telescopically receiving housing41. Outer sleeve42is configured with respect to the housing such that axially displacing the outer sleeve towards the housing open end, by for example manual manipulation, or biting action due to the closing of the jaws, causes opposing sides of the splayed housing41to converge and the array of micro-needles12in each device10a,10bto penetrate the gingival tissue at the treatment site. It also causes the capsule11within the respective delivery device to rupture and thereby to deliver the drug to the gingival and/or oral mucosal tissue, as shown at (a), (b) and (c) inFIG. 8.

FIG. 9illustrates a drug delivery assembly similar to that ofFIG. 8, but including a releasable retainer device for retaining the outer sleeve42in its axially-displaced position with respect to housing41, and for selectively releasing the outer sleeve from its retained position. Thus, as shown inFIG. 9, housing41is formed with a plurality of annular recesses41a-41nspaced along its length for selectively receiving a rib42aformed on the inner surface of the sleeve42adjacent its upper open end. Sleeve42is somewhat elastic to permit its rib42ato snap into a selected recess41a-41nof housing41, and also to be forcefully unseated from the recess. The lower end of sleeve42may be formed with another annular rib42bsqueezable between two fingers of the user in order to deform the bottom wall42c, and thereby to facilitate the unseating of rib42afrom a selected recess41a-41n.

FIG. 10illustrates a drug delivery device, generally designated50, similar to that ofFIG. 9, and various stages in its use as illustrated inFIG. 8. The device illustrated inFIG. 10also includes a splayed housing51open at one end and configured to be applied to a patient's tooth and supporting soft tissues, and an outer sleeve52telescopically receiving the housing and axially displaceable with respect to the housing for activating the device. The illustrated device further includes a micro-needle array53a,53bcarried on each of the opposite faces of the inner surface of housing51, and a capsule54containing a quantity of the drug to be delivered enclosed within a rupturable film.

In the drug delivery device illustrated inFIG. 10, however, the capsule54is received within a cavity55formed in the end wall closing the bottom of housing51. Cavity55communicates with each of the two micro-needle arrays53a,53bvia passageways56a,56bformed in the side walls of housing51.

Housing51, and sleeve52telescopically received thereover, are otherwise similarly constructed as described above with respect toFIGS. 8 and 9. Thus, housing51includes a plurality of annular recesses, e.g.,51q; and sleeve52includes an annular rib52areceivable within a selected recess for releasably retaining the sleeve in an actuated position on the housing. Sleeve52is also formed with the annular rib52bsqueezable by the user's fingers in order the release the sleeve from the housing. In this case, however, the bottom wall52cof sleeve52is configured such that, after the sleeve has been moved from a lower position, as shown at (a), to an intermediate position to cause the micro-needle arrays53a,53bto pierce the tissue at the treatment site, as shown at (b) inFIG. 10, the sleeve may be further moved to its uppermost position, wherein its rib52aseats in the upper annular recess51a, to cause the bottom wall52cof the sleeve to engage the capsule54and to rupture the capsule, as well as to force its contents through channels56a,56bto the micro-needle arrays53a,53bas shown at (c) inFIG. 10.

TheFIG. 10construction thus not only better assures that the capsule will be ruptured only after the micro-needle arrays penetrate the tissue at the treatment site, but also enables the housing to be of a more compact construction since it accommodates the capsule in the end wall of the housing, rather than at the two side walls adjacent to the micro-needle arrays.

FIG. 11illustrates a drug delivery device of similar construction as inFIG. 10, and various stages in its use as described above with respect toFIG. 10, except that instead of providing the housing51with a single cavity55for receiving a single capsule54, the housing is provided with two cavities55a,55b, each for receiving a separate capsule54a,54b, each communicating with one of the passageways56a,56bwith one of the micro-needle arrays53a,53b. Providing a separate capsule for each micro-needle array better assures a more even distribution of the drug to the treatment site via the two arrays.

A feature of all the designs illustrated inFIGS. 8-11is the ability to vary the position of the micro needle arrays with respect to the bottom (crown) of the teeth. It is important to be able to accurately position the micro-needles over the supporting tissues surrounding the teeth, i.e. the gingivea and oral mucosal tissues; however this location relative to the tooth's crown the can vary from case to case. In order to be able to adjust the height of the micro-needles relative to the tooth crown, a series of sponge pad inserts57of different thicknesses may be selectively inserted into the space58, as shown inFIG. 12.

By using hydrogel bodies with increased thickness, which are saturated with a solution of an appropriate medication (such as the anesthetic lidocaine), and a source of DC current wired to the hydrogel bodies, it is possible to iontophoretically drive significant amounts of the medicine into the underlying tissues, even in the absence of the micro-needle and drug containing capsule arrangements, when using supporting devices of the type illustrated inFIGS. 8-12, wherein the micro-needle arrays are replaced by the hydrogel bodies with increased thickness, which are saturated with a solution of an appropriate medication. In this manner, the application of electrical current would be initiated only after a predefined level of pressure had been reached during the clamping process described for the designs ofFIGS. 8-12.

If the two sides of the devices are to be used for this purpose, then the polarity of the DC current may be reversed at appropriate intervals to cause the medicine to be delivered to both sides. Alternatively, a third electrode to be applied at a different body site, may be used, in which case the iontophoretic delivery may be applied simultaneously to both sides of the tooth or teeth being treated.

Iontophoresis could be used in the manner described above, or could be used in conjunction with the hollow micro-needle array and capsule arrangement as a source of the drug.

It is also possible to simply use hydrogel bodies, which are saturated with a solution of an appropriate medication, in combination with either solid or hollow micro-needle, when using any of described devices in order to augment the delivery of the drug. In this manner, the perforation of the body surface by the micro-needles and the positive force applied to the hydrogel body or bodies would augment the transfer of the drug from the hydrogel source to the underlying tissues by making the body surface more permeable, and by applying a positive pressure gradient to the drug held in the hydrogel. This process could be performed either with or without drug containing capsule arrangements shown in those figures. This most particularly applicable in the cases of those designs having a compressible sponge component, i.e. those shown in FIGS.2and5-12inclusive, which provide ongoing force even in the absence of user applied force, following their initial application.

Drug coated solid micro-needles known to the art could likewise be used for trans-gingival drug delivery when using supporting devices of the type illustrated inFIGS. 8-12. Likewise, they could be used for surface drug delivery when using supporting devices of the type illustrated inFIG. 1,FIGS. 2a-2cand inFIGS. 5-7, and would be especially effective when used in combination with drug saturated hydrogels as described above.

FIG. 13illustrates a drug delivery device constructed in accordance with the present invention particularly useful for delivering a drug beyond the surface of an internal body lumen, such as a wall of the respiratory tract, of the alimentary tract, of the urogenital tract, or of an arterial or a venous blood vessel. In this case, the drug delivery device is carried by a catheter to enable its manipulation to the treatment site, and is activated at the treatment site by the inflation of a balloon.

As shown inFIG. 13, the drug delivery device, therein generally designated60, includes a carrier member in the form of a catheter tube61formed with a central passageway62. Passageway62may serve for the insertion of a guide wire, as a conduit for the tube or tubes63ainflating the balloon or balloons, for the administration of materials such as contrast media or for the administration of drugs to the distal intra-luminal space, as well as for the insertion of an endoscope, etc.

The drug delivery device60is sized for insertion into the respective lumen. It includes an inner balloon63which is connected to tube63afor facilitating filling or emptying of the balloon and is attached to at least one drug delivery device of the type described above. The illustrated drug delivery device comprises a rupturable film capsule or closed bag64containing the drug to be administered, a mesh layer65thereover, an outer array of micro-needles66oriented such that the micro-needles face the treatment site and an outer deformable layer68overlying the opposite side of the capsule. The outer deformable layer68has an outer peripheral edge secured to the outer peripheral edge of the micro-needle array66. As stated, the micro-needle array, drug filled capsule, mesh layer and outer cover construction described above overlying balloon63are essentially similar to the various devices illustrated inFIGS. 1 and 2above.

Drug delivery device60further includes a pair of contoured abutments67a,67b, straddling the opposite sides of the foregoing elements to facilitate the manipulation of the drug delivery device through the lumen to the treatment site.

To further facilitate the unimpeded transfer of the drug delivery device to the intended treatment site, and to avoid unintentional contact between the micro needles and the lumen surface during the process of transferring the device to the intended treatment site, a compressible sponge layer69is placed between said micro-needles such that its upper side extends to the top of the micro-needles. Compressible sponge layer69is firmly adhered to the micro-needle array to prevent its dislodgement in the lumen.

It will be appreciated that balloon63is in a deflated condition during the manipulation of the drug delivery device60to the treatment site. Upon reaching the treatment site, balloon63is inflated to thereby cause the micro-needles to compress sponge layer69and to penetrate the tissue at the treatment site, and the capsule64to rupture and to deliver the drug to the treatment site via the passageways of the micro-needle array, as described above. Following completion of the drug delivery process, micro-needle array66is withdrawn from the lumen wall by actively deflating balloon63so as to cause the micro-needle array to retract, and allow sponge layer69to then re-expand to again prevent unintentional contact between the micro needles and the lumen surface during the process of withdrawing the device.

The foregoing elements63-69of the drug delivery device are preferably of an annular configuration so as to uniformly distribute the drug to an annular surface at the treatment site. It will be appreciated, however, that the foregoing elements may be of a non-annular or segmented configuration, e.g., where the drug is to be delivered to a non-annular region. It will be further appreciated that more than a single micro-needle based drug delivery unit may be employed, that these may be of varying sizes, and that this invention could be implemented using MEM (microelectronic machining) technology.

Accordingly, the invention has been described with respect to several preferred embodiments, it will be understood that these are set forth merely for purposes of example, and that many other variations, modifications and applications of the invention may be made.