Microneedle devices

Abstract

The invention relates to a process for preparing a microneedle device comprising providing a mould having a plurality of microdepressions, each of which defines a microneedle, filling the microdepressions with a first dry material, exposing the filled microdepressions to an aqueous fluid and allowing the aqueous fluid to permeate through the filled microdepressions; and optionally curing the filled microdepressions. The process may comprise a step of compressing the filled microdepressions before or after the step of exposing the filled microdepressions to an aqueous fluid. The first dry material may comprise a compound of interest such as ascorbic acid or nicotinamide dispersed therein. The mould is preferably formed of polydimethylsiloxane (PDMS). Preferred first dry materials are hyaluronic acid, sodium hyaluronate, magnesium silicate, magnesium hydroxide and corn starch. The aqueous fluid may be provided as an aqueous gel, particularly an aqueous polymeric gel or hydration may occur suing liquid water or water vapour (humidity hydration). The polymer utilised in the aqueous gel is preferable hyaluronic acid, sodium hyaluronate or polyvinyl alcohol. Microneedle devices prepared according to this process, and the use of the microneedle devices for administration of one or more compounds into a biological tissue of a subject are also described.

Description

B ACKGROUND Microneedles are an array of very small needles typically with lengths in the micrometer range (i.e. less than 1000 micrometers), which are commonly used for the transport of therapeutic, diagnostic, cosmetic, biological or other compounds across biological tissue, such as the skin. Microneedles work by creating tiny pores within the biological tissue of an individual through which compounds can be delivered directly into the epidermis or dermis of said individual. This direct delivery of a compound to the epidermis or dermis of an individual results in the compound coming into quick and direct contact with biological mediums (e.g. sweat, sebum, interstitial fluid) located in the epidermis or dermis. Upon dissolution in these biological mediums, the compounds are then diffused into the epidermis or dermis and in turn throughout the body of the individual. This mechanism by which microneedles work means they generally result in quicker delivery of compounds to an individual compared to conventional administration routes, such as topical administration. Microneedles also tend to allow for large molecules (e.g. molecules with a molecular weight of greater than 500 Daltons) to be more easily delivered through the skin into biological mediums than is achievable using conventional administration routes such as topical administration, where a diffusion limit of circa. 500 Daltons typically exists. There are several types of microneedles known in the art, and these include: solid microneedles, hollow microneedles, coated microneedles, dissolving microneedles, and hydrogel microneedles. Dissolving microneedles (DMNs), for example, are generally formed from materials (e.g. biologically friendly polymeric materials) which readily dissolve when inserted into the biological tissue. Dissolving microneedles thus do not tend to leave sharp needle waste and harmful material in the biological tissue after administration of the desired compound(s). The present invention relates to a process for preparing a microneedle device, microneedle devices prepared according to said process, and the use of said microneedle devices for administration of one or more compounds into a biological tissue of a subject. SUMMARY At its most general, the invention relates to a process for preparing a microneedle device. The inventors have found that fdling a microneedle mould a first dry material and then exposing this dry material to a specific amount of aqueous fluid allows microneedles with good physical properties to be prepared in a quick, cheap and scalable manner. Accordingly, in a first aspect of the invention, there is provided a process for preparing a microneedle device comprising: providing a mould having a plurality of microdepressions, each of which defines a microneedle; filling the microdepressions with a first dry material; exposing the filled microdepressions to an aqueous fluid and allowing the aqueous fluid to permeate through the filled microdepressions; and optionally curing the filled microdepressions. Further features of the process, such as the first dry material, the aqueous fluid and the conditions for each step, are set out below. The inventors have also found that novel microneedle devices may be prepared using the process of the first aspect. Accordingly, in a second aspect of the invention, there is provided a microneedle device prepared according to the process defined in the first aspect. According to a third aspect of the invention, there is provided a microneedle device comprising: a base; an array of microneedles, where the microneedles are formed from a first material; and a layer of a second polymeric material located between the base and the array of microneedles, such that the array of microneedles is located on one side of the layer of a second polymeric material and the base is located on the other side of the layer of a second polymeric material. The inventors have also found that the microneedle devices of the second or third aspect are useful in delivering one or more compounds into a biological tissue. Accordingly, in a fourth aspect of the invention, there is provided a microneedle device for administration of one or more compounds into a biological tissue prepared according to process defined in the first aspect. In a fifth aspect of the invention, there is provided the use of a microneedle device according to the second or third aspect for administration of one or more compounds into a biological tissue of a subject. These and other aspects and embodiments of the invention are described in further detail below. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1 shows a schematic representation of the steps involved in the process of the invention. Figure 2 shows a picture of a microneedle device prepared according to the process of the invention, as per Example 1 described hereinbelow. Figure 3 shows an enlarged picture of the microneedle device shown in Figure 2. Figure 4 shows a picture of microneedles prepared by hydrating polymeric powder filled microdepressions with water and curing the hydrated polymeric powders for 24 hours, as per Example 2 described hereinbelow. 5 Figure 5 shows a picture of microneedles prepared by exposing polymeric powder filled microdepressions with water vapour before curing the hydrated polymeric powders for 24 hours, as per Example 3 described hereinbelow. Figure 6 shows an enlarged picture of the microneedle device shown in Figure 5. 10 Figure 7 shows a picture of microneedles prepared from magnesium silicate powder as per Example 4 described hereinbelow. Figure 8 shows an enlarged picture of the microneedle device prepared from magnesium 15 hydroxide powder as per Example 5 described hereinbelow. Figure 9 shows a picture of microneedles prepared from com starch powder as per Example 6 described hereinbelow. 20 DETAILED DESCRIPTION The invention relates to a process for preparing a microneedle device (for example, 108 as shown in step 4 of Fig. 1), and to microneedle devices prepared using this process. Also provided is the use of the microneedle devices prepared using the process of the invention for administration of one or more compounds into a biological tissue of a subject. 25 The following features may apply to all aspects of the invention as described above. The features may be combined in any combination. Providing a Mould 30 Moulds for the preparation of microneedles (for example, 110 as shown in step 1 of Fig. 1) are well known in the art and include, for example, moulds made from silicone, metal and polymeric materials. It will be appreciated that all such known moulds are contemplated for use herein. In certain embodiments, the moulds are silicone moulds, such as moulds prepared from polydimethylsiloxane (PDMS). The moulds used in the process of the invention may be pre-made, commercially available moulds, or they may be prepared in situ using well known methodology. Ine r irst Dry Material The first dry material (for example, 102 as shown in step 1 of Fig. 1) may comprise a polymer or a polymerizable compound. In embodiments where the first dry material comprises a polymer, it will be appreciated that the first dry material may comprise more than one polymer. It will be appreciated that any polymer suitable for the preparation of microneedles may be used. In certain embodiments, the microneedles prepared by the process of the invention are dissolving microneedles. Thus, in certain embodiments, the polymer is a biocompatible polymer that is capable of dissolving in the presence of moisture within the biological tissue of an individual. Biocompatible polymers suitable for preparing dissolving microneedles are well known within the art, and all such materials are contemplated for use herein. In certain embodiments, the first dry material comprises a polymer selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethyl cellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methylcellulose, polyethylene glycol, gelatin, polycaprolactone and combinations thereof, for example, the first dry material comprises a polymer selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof (e.g. the first dry material comprises hyaluronic acid). In some embodiments, the first dry material comprises a polymerizable compound. It will be appreciated that the first dry material may comprise more than one polymerizable compound. The polymerizable compound(s) may be any monomeric compound(s) which is capable of being polymerized to form a polymer as defined above. For example, the polymerizable compound(s) may be a monomeric compound(s) which undergoes polymerization to form a polymer(s) as defined above. In certain embodiments, one or more polymerization initiators may be added before, during or after the step of exposing the filled microdepressions to an aqueous fluid and before the step of optionally curing the filled microdepressions. It will be appreciated that said polymerization initiator(s) may be added to help initiate polymerization of the polymerizable compound(s). Suitable polymerisation initiators are well known in the art, and all such polymerization initiators are contemplated for use herein. Non-limiting examples of suitable polymerization initiators include radical initiators (such as peroxides and azido compounds), anionic initiators (such as alkoxides, cyanides, phoshines, amines and organometallic compounds) and cationic initiators (such as Lewis acids including SNCh, AlCh, BF3 and TiCh). In some embodiments, the process of the invention may additionally comprise a step of exposing the filled microdepressions to UV light to initiate polymerization of the polymerizable compound(s). The skilled person will be able to select suitable conditions to use for the step of exposing the filled microdepressions with UV light, when this step is present. In some embodiments, the first dry material comprises a non-polymeric compound. Nonlimiting examples of possible non-polymeric compounds include charcoal, magnesium oxide, magnesium hydroxide, aluminium oxide, magnesium silicate, com starch and combinations thereof. In certain embodiments the non-polymeric compound is charcoal. The first dry material is a dry material. Thus, the first dry material may have a moisture content of less than 20%, such as less than 10%, or such as less than 8%, or such as less than 5% or such as less than 3%. In some embodiments, the first dry material has a moisture content of between 0.01% and 20%, such as between 0.1% and 10%, or such as between 0.5% and 8%. In certain embodiments, the first dry material is a solid material, such as a powdered or granular material. In some embodiments, the first dry material is a powdered material. Thus, in certain embodiments, the first dry material comprises one or more of the above polymers or polymerizable compounds in powdered form. It will be appreciated that the first dry material may have any suitable size. In certain embodiments, the first dry material is a powdered material with an average (mean) particle size of less than 100 pm, such as less than 50 pm, or such as less than 10 pm, or less than 1 pm, or less than 0.5 pm. In some embodiments, the first dry material is a powdered material with an average (mean) particle size of between 0.001 pm and 100 pm, such as between 0.01 pm and 10 pm, or between 0.01 pm and 1 pm, or between 0.01 pm and 0.5 pm. The average (mean) particle size of the first dry material may affect how well the first dry material enters and completely fills the mould cavities, particularly in embodiments where the mould cavities include a sharp sub-micron tip. In certain embodiments, the first dry material further comprises one or more compounds of interest. The compounds of interest may be any compounds that are suitable for administration into a biological tissue of a subject (e.g. human). For example, the compounds of interest may be any suitable therapeutic compound, diagnostic compound, cosmetic compound, biological compound or similar. In certain embodiments, compounds of interest may be selected from cosmetic agents, vitamins, herbs, dietary supplements, humectants, active pharmaceutical ingredients, allergens, diagnostic agents, markers (e.g., coloured dyes or radiological dyes or inks comprising coloured dyes), and any other compound that is desirable to introduce into a biological tissue. In some embodiments, the biological tissue is a tissue of a human or other mammal, including but not limited to the skin of a human or other mammal. In one embodiment, the compounds of interest may be selected from a cosmetic agent, vitamin, herb, or dietary supplement known in the art. Non-limiting examples include ascorbic acid, salicylic acid, nicotinamide, vitamin B3, niacinamide, hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid, vitis vinifera (grape) seed extract, portulaca orelacea (duckweed or little hogweed) purslane extract, madecassoside (centella asiatica, also known as Tiger Grass or gotu kola), Panax Ginseng Root Extract, Carnosine, Astragalus Membranaceus Extract, Adenosine, Tocopheyl Acetate (vitamin E), Bakuchiol, Palmitoyl Pentapeptide-4, Retinol, Polydeoxyribonucleotide, Anthemis Nobilis (chamomile) flower extract, Arbutin, Glycyrrhiza Glabra (licorice) root extract, Kojic acid, Ferulic acid, Oxidized Glutathione, Glutathione, Ascorbyl glucoside, Camellia Sinensis (Green Tea) leaf extract, Centella Asiatica extract, magnesium ascorbyl phosphate, coumaric acid, tranexamic acid (synthetic lysine amino acid), zingiber officinale (ginger) root extract, Phoenix Dactylifera seed, Chenopodium Quinoa seed extract, kawarayomogi (Korean mugwort) leaf extract, Artemisia princeps (Japanese Mugwort / worm wood) leaf extract, olive oil or juice (also known as Olea Europaea Fruit Oil) 5-HTP (5-hy dr oxy try ptophan), acai berry, acetyl-L-camitine, activated charcoal, aloe vera, alpha-lipoic acid, apple cider vinegar, arginine, ashitaba, ashwagandha, astaxanthin, barley, bee pollen, beta-alanine, beta-carotene, beta-glucans, biotin, bitter melon, black cherry, black cohosh, blackcurrant, black tea, branched-ahain amino acids, bromelain (bromelin), calcium, camphor, chamomile, chasteberry, chitosan, chlorella, chlorophyll, choline, chondroitin, chromium, cinnamon, citicoline, coconut water, coenzyme Q10, conjugated linoleic acid, cordyceps , cranberry, creatine, D-mannose, damiana, deer velvet, DHEA, DMSO, echinacea , EDTA, elderberry, emu Oil, evening primrose oil, fenugreek, feverfew, folic acid, forskolin, GABA (gamma-aminobutyric acid), gelatin, ginger, ginkgo biloba, ginseng, glycine, glucosamine, glucosamine sulfate, glutathione, gotu kola, green coffee, guarana, guggul, gymnema, hawthorn, hibiscus, holy basil, horny goat weed, inulin, iron, krill oil, L-camitine, L-citrulline, L-trypotophan, lactobacillus , magnesium, magnolia , milk thistle, MSM (methylsulfonylmethane), niacin, olive, omega-3 fatty acids, oolong tea, oregano, passionflower, pectin, phenylalanine, phosphatidylserine, potassium, probiotics, progesterone, quercetin, ribose, red yeast rice, reishi mushroom, resveratrol, rosehip, saffron, SAM-e, saw palmetto, schisandra, sea buckthorn, selenium, senna, slippery elm, St. John's wort, stinging nettle, tea tree oil, theanine, tribulus terrestris , turmeric (curcumin), tyrosine, valerian, vitamin A, vitamin Bl2, vitamin D, vitamin K, vitamin B6 (pyridoxine), whey protein, witch hazel, xanthan gum, xylitol, yohimbe, zinc, lutein, dexpanthenol, liquorice root extract, Indian pennywort extract, ginsenosides, superoxide dismutase, acetyl hexapeptide-3, oligopeptide-68, palmitoyl tetrapeptide-7 and combinations thereof. In some embodiments, the compounds of interest are selected from a cosmetic agent, vitamin, herb, or dietary supplement selected from ascorbic acid, salicylic acid, nicotinamide, vitamin B3, niacinamide, hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid, vitis vinifera (grape) seed extract, portulaca orelacea (duckweed or little hogweed) purslane extract, madecassoside (centella asiatica, also known as Tiger Grass or gotu kola), Panax Ginseng Root Extract, Carnosine, Astragalus Membranaceus Extract, Adenosine, Tocopheyl Acetate (vitamin E), Bakuchiol, Palmitoyl Pentapeptide-4, Retinol, Polydeoxyribonucleotide, Anthemis Nobilis (chamomile) flower extract, Arbutin, Glycyrrhiza Glabra (licorice) root extract, Kojic acid, Ferulic acid, Oxidized Glutathione, Glutathione, Ascorbyl glucoside, Camellia Sinensis (Green Tea) leaf extract, Centella Asiatica extract, magnesium ascorbyl phosphate, coumaric acid, tranexamic acid (synthetic lysine amino acid), zingiber officinale (ginger) root extract, Phoenix Dactylifera seed, Chenopodium Quinoa seed extract, kawarayomogi (Korean mugwort) leaf extract, Artemisia princeps (Japanese Mugwort / wonnwood) leaf extract, olive oil or juice (also known as OleaEuropaea Fruit Oil), vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, vitamin B6 (pyridoxine), whey protein, witch hazel, xanthan gum, xylitol, yohimbe, zinc, lutein, dexpanthenol, liquorice root extract, Indian pennywort extract, ginsenosides, superoxide dismutase, acetyl hexapeptide-3, oligopeptide-68, palmitoyl tetrapeptide-7 and combinations thereof. In some embodiments, the compounds of interest are selected from a cosmetic agent, vitamin, herb, or dietary supplement selected from ascorbic acid, salicylic acid, nicotinamide, vitamin B3, niacinamide, hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid, vitis vinifera (grape) seed extract, portulaca orelacea (duckweed or little hogweed) purslane extract, madecassoside (centella asiatica, also known as Tiger Grass or gotu kola), Panax Ginseng Root Extract, Carnosine, Astragalus Membranaceus Extract, Adenosine, Tocopheyl Acetate (vitamin E), Bakuchiol, Palmitoyl Pentapeptide-4, Retinol, Polydeoxyribonucleotide, Anthemis Nobilis (chamomile) flower extract, Arbutin, Glycyrrhiza Glabra (licorice) root extract, Kojic acid, Ferulic acid, Oxidized Glutathione, Glutathione, Ascorbyl glucoside, Camellia Sinensis (Green Tea) leaf extract, Centella Asiatica extract, magnesium ascorbyl phosphate, coumaric acid, tranexamic acid (synthetic lysine amino acid), zingiber officinale (ginger) root extract, Phoenix Dactylifera seed, Chenopodium Quinoa seed extract, kawarayomogi (Korean mugwort) leaf extract, Artemisia princeps (Japanese Mugwort / wormwood) leaf extract, olive oil or juice (also known as Olea Europaea Fruit Oil), vitamin A, vitamin B12, vitamin C, vitamin D, vitamin K, vitamin B6 (pyridoxine), whey protein, witch hazel, xanthan gum, xylitol, yohimbe, zinc and combinations thereof. In certain embodiments, the compounds of interest are selected from ascorbic acid, salicylic acid, nicotinamide, hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid and combinations thereof. In some embodiments, the compounds of interest may be a prophylactic, therapeutic, or diagnostic agent useful in medical or veterinary application. Thus, in certain embodiments, the compounds of interest may be a prophylactic or therapeutic substance, which may be referred to herein as an active pharmaceutical ingredient (API). In certain embodiments, the API is selected from proteins, peptides and fragments thereof, which can be naturally occurring, synthesized or recombinantly produced. Representative examples of types of API for delivery include antibiotics, antiviral agents, analgesics, anesthetics, antihistamines, anti-inflammatory agents, anticoagulants, allergens, vitamins, antineoplastic agents. In one embodiment, compounds of interest may be a vaccine. Non-limiting examples of suitable vaccines include vaccines for infectious diseases, therapeutic vaccines for cancers, neurological disorders, allergies, and smoking cessation or other addictions. In certain embodiments the vaccine may be a vaccine for the prevention of anthrax, cervical cancer (human papillomavirus), dengue fever, diphtheria, Ebola, hepatitis A, hepatitis B, hepatitis C, haemophilus influenzae type b (Hib), HIV / AIDS, human papillomavirus (HPV), influenza (seasonal and pandemic), Japanese encephalitis (JE), lyme disease, malaria, measles, meningococcal, monkeypox, mumps, pertussis, pneumococcal, polio, rabies, rotavirus, rubella, shingles (herpes zoster), smallpox, tetanus, typhoid, tuberculosis (TB), varicella (chickenpox), West Nile, and yellow fever. In another embodiment, compounds of interest may be a therapeutic agent. The therapeutic agent may be selected from small molecules and larger biotechnology produced or purified molecules (e.g., peptides, proteins, DNA, RNA). Examples of therapeutics include but are not limited to insulin, insulin-like growth factor, insultropin, parathyroid hormone, pramlintide acetate, growth hormone release hormone, growth hormone release factor, mecasermin, Factor VIII, Factor IX, antithrombin III, protein C, protein S, P-gluco-cerebrosidase, alglucosidase-a, laronidase, idursulphase, galsulphase, agalsidase-P, a-1 proteinase inhibitor, lactase, pancreatic enzymes, adenosine deaminase, pooled immunoglobulins, human albumin, erythropoietin, darbepoetin-a, filgrastim, pegfilgrastim, sargramostim, oprelvekin, human follicle-stimulating hormone, human chorionic gonadotropin, lutropin-a, interferon (alpha, beta, gamma), aldesleukin, alteplase, reteplase, tenecteplase, urokinase, factor Vila, drotrecogin-a, salmon calcitonin, exenatide, octreotide, dibotermin-a, recombinant human bone morphogenic protein 7, histrelin acetate, palifermin, becaplermin, trypsin, nesiritide, botulinum toxin (types A and B), collagenase, human deoxyribonuclease I, hyaluronidase, papain, 1-asparaginase, pegasparaginase, rasburicase, lepirudin, bivalirudin, streptokinase, anistreplase, bevacizumab, cetuximab, panitumumab, alemtuzumab, rituximab, trastuzumab, abatacept, anakinra, adalimumab, etanercept, infliximab, alefacept, efalizuman, natalizumab, eculizumab, antithymocyte globulin, basiliximab, daclizumab, muromonab-CD3, omalizumab, palivizumab, enfuvirtide, abciximab, pegvisomant, crotalidene polyvalent fab (ovine), digoxin immune serum fab (ovine), ranibizumab, denileukin diftitox, ibritumomab tiuxetan, gemtuzumab ozogamicin, tositumomab, I-tositumomab, anti-rhesus (rh) immunoglobulin G, desmopressin, vasopressin, deamino [Val4, D-Arg8] arginine vasopressin, somatostatin, somatotropin, bradykinin, bleomycin sulfate, chymopapain, glucagon, epoprostenol, cholecystokinin, oxytocin, corticotropin, prostaglandin, pentigetide, thymosin alpha-1, alpha-1 antitrypsin, fentanyl, lidocaine, epinephrine, sumatriptan, benztropine mesylate, liraglutide, fondaparinux, heparin, hydromorphone, omacetaxine mepesuccinate, pramlintide acetate, thyrotropin-alpha, glycopyrrolate, dihydroergotamine mesylate, Bortezomib, triptoreline pamaote, teduglutide, methylnaltrexone bromide, pasireotide, ondansetron hydrochloride, droperidol, triamcinolone (hex)acetonide, aripiprazole, estradiol valerate, morphine sulfate, olanzapine, methadone hydrochloride, and methotrexate. The compounds of interest may be present in any suitable amount. In some embodiments, the compounds of interest are present in an amount of between 0.1% and 40% based on the total weight of the first dry material, such as between 0.1% and 20% based on the total weight of the first dry material, or between 0.5% and 15% based on the total weight of the first dry material, or between 0.5% and 10% based on the total weight of components, or between 1% and 8% based on the total weight of the first dry material. In some embodiments, the first dry material comprises more than one compound, where one of the compounds is present in an amount greater than 20% based on the total weight of the first dry material and each of the other compounds is present in an amount less than 10% based on the total weight of the first dry material. It will be appreciated that in embodiments where the first dry material comprises more than one compound (e.g. a polymer and one or more compounds of interest) each compound may be added to the microdepressions of the mould either together or separately. It will be appreciated that the microdepressions may be filled with the first dry material in any suitable manner. In some embodiments, after filling the microdepressions with the first dry material, the process may comprise a step of compressing the filled microdepressions before the step of exposing the filled microdepressions to an aqueous fluid. In some embodiments, the step of filling the microdepressions with the first dry material and compressing the filled microdepressions may be repeated before the step of exposing the filled microdepressions to an aqueous fluid. It will be appreciated that any suitable conditions to compress the filled microdepressions may be used. In certain embodiments, after filling the moulds with the first dry material, the process comprises a step of compressing the filled microdepressions using a force of at least 145N (such as at least 150N, or at least 160N, or at least 170N) before the step of exposing the filled microdepressions to an aqueous fluid. Exposing the Filled Microdepressions to an Aqueous Fluid After filling the microdepressions with a first dry material, the filled microdepressions are then exposed to an aqueous fluid. It will be appreciated that the action of exposing the filled microdepressions to an aqueous fluid results in a portion of the aqueous fluid permeating through the filled microdepressions. This allows the first dry material to become hydrated. The action of hydrating the first dry material allows the first dry material to swell, and in some cases become entangled, which helps to increase the structural integrity of the microneedles, once formed. It will be understood that the term aqueous fluid refers to any liquid, solution, gel or vapour comprising water. In some embodiments, the aqueous fluid is a gel comprising water, such as a hydrogel (e.g., hydrogel 104 as shown in step 2 of Fig. 1). Thus, the aqueous fluid may be a hydrogel comprising one or more of the polymers or polymerizable compounds described below. In other embodiments, the aqueous fluid is a vapour comprising water, such as steam or water vapour. In some embodiments, the aqueous fluid is not an aqueous solution or water alone. It will be appreciated that any suitable amount of aqueous fluid may be used. In certain embodiments, the amount of water in the aqueous fluid is between 0.1% and 100% based on the weight of the first dry material, such as between 0.1% and 80% based on the weight of the first dry material, or between 0.1% and 60% based on the weight of the first dry material, or between 0.1% and 50% based on the weight of the first dry material, or between 0.1% and 40% based on the weight of the first dry material, or between 1% and 30% based on the weight of the first dry material, or between 5% and 20% based on the weight of the first dry material. Thus, the amount of aqueous fluid used in the step of exposing the filled microdepressions to an aqueous fluid corresponds to an amount capable of delivering water to the first dry material based on the (dry) weight of the first dry material in any of the amounts recited above (e.g between 0.1% and 80%). It will be appreciated that the aqueous fluid in addition to comprising water may comprise one or more additional compounds. Non-limiting examples of possible additional compounds include polymers, polymerizable compounds, oils, wetting agents, etc. In certain embodiments, the aqueous fluid in addition to comprising water further comprises one or more of the compounds of interest as described hereinabove. Thus, in certain embodiments, the aqueous fluid may comprise a second polymer or second polymerizable material, wherein the second polymer or second polymerizable material may be the same and / or different to the polymer or polymerizable compounds of the first dry material. In certain embodiments, the aqueous fluid comprises one or more polymers selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethyl cellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methylcellulose, polyethylene glycol, gelatin and combinations thereof. The aqueous fluid may comprise one or more polymers selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, polyvinylpyrrolidone and combinations thereof. Thus, in some embodiments, the aqueous fluid is a gel (hydrogel) comprising one or more polymers selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethyl cellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methylcellulose, polyethylene glycol, gelatin and combinations thereof, such as one or more polymers selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof. It will be appreciated that the aqueous fluid may comprise any suitable amount of water. The water content of the aqueous fluid will depend on the nature of both the aqueous fluid (e.g. whether it is a gel or vapour) and the nature of the first dry material. In certain embodiments, the aqueous fluid may comprise greater than 20%, or greater than 30%, or greater than 40%, or greater than 50%, or greater than 60%, or greater than 70% water based on the total weight of the aqueous fluid. In a specific embodiment, the aqueous fluid may comprise approximately 50% water based on the total weight of the aqueous fluid. In some embodiments, the aqueous fluid will comprise between 10% and 99.9%, or between 30% and 99.9%, or between 40% and 99 %, or between 50% and 95%, or 60% and 95% water based on the total weight of the aqueous fluid. In some embodiments, the aqueous fluid is a gel comprising water, such as a hydrogel, and the gel comprises between 10% and 99.9%, or between 30% and 99.9%, or between 40% and 99 %, or between 50% and 95%, or 60% and 95% water based on the total weight of the gel. In certain embodiments, the aqueous fluid is a gel comprising water and one or more polymers, such as those described above. Thus, in some embodiments, the aqueous fluid is a hydrogel comprising hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof, wherein the hydrogel comprises between 30% and 99.9% of water based on the total weight of the aqueous fluid. In embodiments where the aqueous fluid is a gel comprising water (e.g. a hydrogel), the volume of gel used in the step of exposing the filled microdepressions to an aqueous fluid is in the range of 0.005 mL to 0.5 mL, such as in the range of 0.01 mL to 0.3 mL, or in the range of 0.02 mL to 0.2 mL, or in the range of 0.01 mL to 0.1 mL. In one example, the volume of the first dry material may be approximately 1% of the total volume of the mixture of the aqueous fluid and the first dry material. In embodiments where the aqueous fluid comprises one or more polymers, it will be appreciated that these polymers may be the same or different polymers to those polymers of the first dry material. Thus, in some embodiments, the first dry material comprises one or more polymers as defined above and the aqueous fluid (e.g. gel) comprises one or more polymers as defined above, and the polymers of the first dry material are different to the polymers of the aqueous fluid. In other embodiments, the first dry material comprises one or more polymers as defined above and the aqueous fluid (e.g. gel) comprises one or more polymers as defined above, and the polymers of the first dry material are the same as the polymers of the aqueous fluid. In certain embodiments, the first dry material comprises one or more polymers selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof, and the aqueous fluid (e.g. gel) comprises one or more polymers selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof. In some embodiments, the first dry material comprises hyaluronic acid, and the aqueous fluid (e.g. gel) comprises hyaluronic acid. It will be appreciated that the polymers, such as hyaluronic acid, used in both the first dry material and the aqueous fluid may have the same or different average molecular weights. The step of exposing the filled microdepressions to an aqueous fluid may be conducted under any suitable conditions (e.g. temperature, pressure, humidity and duration). The skilled person will be able to select suitable conditions to use for the step of exposing the filled microdepressions to an aqueous fluid. In some embodiments, the step of exposing the filled microdepressions to an aqueous fluid is conducted at a temperature of between 10 °C and 60 °C, such as between 15 °C and 50 °C, or between 20 °C and 40 °C. The step of exposing the filled microdepressions to an aqueous fluid may be conducted at atmospheric pressure (1 atmosphere). In certain embodiments, the aqueous fluid is an aqueous gel (e.g. hydrogel) comprising hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof, wherein the aqueous gel (e.g. hydrogel) comprises between 30% and 99.9% of water based on the total weight of the aqueous fluid, and the step of exposing the filled microdepressions to an aqueous fluid comprises adding the aqueous gel (e.g. hydrogel) to the filled microdepressions in an amount of between 0.1% and 50% based on the weight of the first dry material. In some embodiments, the aqueous fluid is an aqueous gel (e.g. hydrogel) comprising hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof, wherein the aqueous gel (e.g. hydrogel) comprises between 30% and 99.9% of water based on the total weight of the aqueous fluid, and wherein the volume of aqueous gel (e.g. hydrogel) used in the step of exposing the filled microdepressions to an aqueous fluid is in the range of 0.01 mL to 0.3 mL. In certain embodiments, the process comprises a step of compressing the filled microdepressions before and / or after the step of exposing the filled microdepressions to an aqueous fluid (e.g., as shown in step 3 of Fig. 1). In embodiments where the aqueous fluid is an aqueous gel, the filled microdepressions may be compressed after the aqueous gel is applied over the microdepressions (see, for example, steps 2 and 3 in Fig. 1). The aqueous gel may help in the compression of the filled microdepressions, hence increasing the compactness of the first dry material within the microdepressions. The conditions for compressing the filled microdepressions are described above. Curing the Filled Microdepressions After the step of exposing the filled microdepressions to an aqueous fluid the filled microdepressions are allowed to cure (e.g., as shown in step 3 of Fig. 1). This step of curing allows the moisture within the aqueous fluid (e.g. gel) to permeate through the filled microdepressions, which in turn helps to hydrate the first dry material. In certain embodiments, the step of curing the filled microdepressions may be conducted by allowing the filled microdepressions to stand for between 1 and 48 hours at a temperature of between 10 °C and 50 °C, such as between 1 and 36 hours at a temperature of between 10 °C and 40 °C, or between 6 and 36 hours at a temperature of between 15 °C and 35 °C, or between 12 and 30 hours at a temperature of between 20 °C and 30 °C (e.g. 22 °C to 26 °C). The step of curing may be conducted at ambient pressure (e.g. at 1 atmosphere). Optional Additional Steps The process of the invention may comprise one or more additional steps. A non-limiting list of possible additional steps include a step of adding a base layer, a step of adding a separation layer, a step of centrifuging the filled moulds, a step of drying the filled moulds, a step of coating the microneedles (once formed), adding an adhesive to the base layer and / or other steps commonly associated with the preparation of microneedles. Such steps are well-known in the art and are contemplated for use herein. In certain embodiments, the process comprises a step of adding a base to the microneedle device (e.g., base 106 as shown in step 3 of Fig. 1). The base forms the foundation of the microneedle array. The base may form a substantially planar sheet or region, having a certain thickness, and one side of the base connects to microneedles and / or the layer formed from the aqueous fluid (e.g. the layer formed from the gel comprising a second polymer). In some embodiments, the base may protrude into the microneedle itself, as is common within the field of microneedle devices. The base may be non-toxic, and does not cause irritation to the biological tissue (e.g. skin) upon contact. The base may have a thickness of between 5 to 10000 microns (pm), such as 100 to 5000 microns (pm), or 100 to 3000 microns (pm). It will be appreciated that the base may be formed from any suitable material that is compatible with and / or known for use in preparing bases for microneedle arrays. Many such materials are known within the art, and all such materials are contemplated for use herein. Thus, the base may be formed from a woven material, non-woven material, a polymer, a synthetic fabric, a natural fabric, different kinds of paper, a hydrocolloid and a combination thereof. Non-limiting examples of suitable materials from which the base may be formed include polydimethylsiloxane (PDMS), acrylic, styrene-methyl methacrylate copolymers, ethylene / acrylic acid, acrylonitrile-butadiene-styrene (ABS), ABS / polycarbonate, ABS / polysulfone, ABS / polyvinyl chloride, ethylene propylene, ethylene vinyl acetate (EVA), nylons (including nylon 6, nylon 6 / 6, nylon 6 / 6-6, nylon 6 / 9, nylon 6 / 10, nylon 6 / 12, nylon 11 and nylon 12), polyacrylate, polybutylene terephthalate (PBT), polycarbonate, polyethylene terephthalate (PET), polyethylene (including low density, linear low density, high density, cross-linked and ultra-high molecular weight grades), polypropylene homopolymer, polypropylene copolymers, polyolefins, polystyrene (including general purpose and high impact grades), polytetrafluoroethylene (PTFE), ethylene-tetrafluoroethylene (ETFE), polyvinyl fluoride (PVF), polyvinylidene fluoride (PVDF), polychlorotrifluoroethylene (PCTFE), polyethylene-chlorotrifluoroethylene (ECTFE), polymethyl methacrylate (PMMA), silicon styrene-acrylonitrile (SAN), elastomers, metal oxides, plastics, foams, paper-based materials, foil-based materials and glass, or any combination thereof. In certain embodiments, the base is formed from one or more polymers that are not readily dissolvable under physiological conditions. In certain embodiments, the base is formed from a non-woven material, such as paper. In some embodiments, the base is formed from a polymer, such as polydimethylsiloxane (PDMS). Methods for adding a base to microneedles are well known in the art, and all such methods are contemplated for use herein. It will also be appreciated that the base may be added either before the microneedles are removed from the mould or after the microneedles are removed from the mould. In embodiments where the base is added after the microneedles are removed from the mould, it will be appreciated that the base may be added before or after the optional step of curing the fdled microdepressions. In certain embodiments, the process of the invention comprises a step of compressing the filled microdepressions directly after the step of exposing the filled microdepressions to an aqueous fluid, and the base may be added before the step of compressing the filled microdepressions. In some embodiments, the base may be added to the microneedles by laminating the microneedles with one or more of the materials capable of forming a base described hereinabove, such as a non-woven material (e.g. paper). In certain embodiments, the step of adding the base comprises the following steps: - adding a composition capable of forming a base to the mould, which composition comprises at least one polymer or polymerizable monomers capable of forming a base; optionally curing the composition; and drying the mould to prepare the microneedle device. It will also be appreciated that the at least one polymer or polymerizable monomers capable of forming a base may be any polymer mentioned above as examples of the base, or any monomer capable of forming said polymers. In some embodiments, the base may contain an adhesive layer (e.g. adhesive ring) to allow for adhesion to the biological tissue (e.g. skin) when the microneedle device is in use. Suitable materials for such adhesive layers (e.g. silicon adhesive rings) are well-known within the art, and all such materials are contemplated for use herein. Thus, in some embodiments, the process of the invention further comprises a step of adding an adhesive layer to the base. In some embodiments, the base may be in direct contact with the microneedles and / or the layer formed from the aqueous fluid (e.g. the gel comprising a second polymer). In other embodiments, one or more other layers may be interposed between the base and the microneedles and / or the layer formed from the aqueous fluid (e.g. the gel comprising a second polymer). For example, one or more separation layers may be interposed between the base and the microneedles and / or the layer formed from the aqueous fluid (e.g. the gel comprising a second polymer). Thus, in some embodiments, the process of the invention comprises a step of adding a separation layer. A separation layer may be understood as being a layer which dissolves (rapidly) upon contact with physiological conditions. Dissolution of the separation layer will be understood as occurring more quickly than the microneedles (e.g. the polymers from which the microneedles are formed), allowing the microneedles to remain embedded within the biological tissue of a subject while the base is removed. Suitable materials for such separation layers are well-known within the art, and all such materials are contemplated for use herein. A non-limiting list of materials from which the separation layer may be made include polyvinyl alcohol (PVA) and / or polyvinyl pyrrolidone (PVP). In some embodiments, the process of the invention comprises a step of centrifuging the filled microdepressions. The step of centrifuging the filled microdepressions may be conducted before and / or after the step of exposing the filled microdepressions to an aqueous fluid. The step of centrifuging the filled microdepressions may be carried out using any suitable centrifugation conditions. The skilled person will be able to select suitable centrifugation conditions based on the nature of the first dry material and the aqueous fluid. In certain embodiments, the step of centrifuging the filled microdepressions is carried out at a centrifugation speed of at least 3500 RPM, such as at least 3800 RPM, or at least 4000 RPM. Here, it will be understood that RPM refers to revolutions per minute. In some embodiments, the step of centrifuging the filled microdepressions is carried out at a centrifugation speed of between 3500 RPM and 10000 RPM, such as between 3500 RPM and 8000 RPM, or between 4000 RPM and 6000 RPM. In certain embodiments, the step of centrifuging the filled microdepressions is carried out at using a Relative Centrifuge Force (RCF) of greater than 1500 g, such as greater than 1800 g, or greater than 1900 g. In some embodiments, the step of centrifuging the filled microdepressions is carried out using a Relative Centrifuge Force (RCF) of between 1500 g and 6000 g, such as between 1500 g and 5500 g, or between 1700 g and 5000 g, or between 1800 g and 4500 g, or between 1800 g and 4000 g. The step of centrifuging the filled microdepressions may be conducted for any suitable duration. The step of centrifuging the filled microdepressions may be carried out for a duration of between 2 minutes and 120 minutes, such as between 2 minutes and 60 minutes, or between 2 minutes and 30 minutes, or between 2 minutes and 20 minutes, or between 2 minutes and 15 minutes, or between 3 minutes and 10 minutes. The step of centrifuging the filled microdepressions may also be conducted at any suitable temperature. In certain embodiments, the step of centrifuging the filled microdepressions is carried out at a temperature of between 10 °C and 40 °C, such as 20°C to 30 °C. In some embodiments, there may be an optional additional step of drying the filled microdepressions after the steps of exposing the filled microdepressions to an aqueous fluid and optionally curing the filled microdepressions. Any suitable technique may be used to dry the filled microdepressions. Thus, the step of drying the filled microdepressions may be conducted at any suitable temperature and for any suitable duration. The step of drying the filled microdepressions may be conducted at a temperature of between 20 °C and 100 °C for a duration of between 1 hour and 48 hours. Thus, the step of drying the filled microdepressions may be conducted at a temperature of between 20 °C and 80 °C for a duration of between 1 hour and 36 hours. For example, the step of drying the filled microdepressions may be conducted at a temperature of between 20 °C and 50 °C for a duration of between 1 hour and 24 hours. That is, the step of drying the filled microdepressions may be conducted at a temperature of between 20 °C and 40 °C for a duration of between 6 hours and 24 hours. That is to say, the step of drying the filled microdepressions may be conducted at a temperature of between 20 °C and 40 °C (e.g. between 20 °C and 25°C) for a duration of between 12 hour and 24 hours. In certain embodiments, the process comprises a further step of de-moulding the cured microneedles 108 (e.g., as shown in step 4 of Fig. 1). Microneedle Devices Accordingly, in a second aspect of the invention, there is provided a microneedle device prepared according to the process defined in the first aspect. The microneedle device of the second aspect may be, for example, a microneedle device for administration of one or more compounds of interest into a biological tissue. Further, according to a third aspect of the invention, there is provided a microneedle device comprising: a base; an array of microneedles, where the microneedles are formed from a first material; and a layer of a second polymeric material located between the base and the array of microneedles, such that the array of microneedles is located on one side of the layer of a second polymeric material and the base is located on the other side of the layer of a second polymeric material. The first material may be a first polymeric material. It will be appreciated that the first polymeric material corresponds to a polymeric material prepared from the polymer or polymerizable compound(s) of the dry material, and that the second polymeric material corresponds to a polymeric material prepared from the second polymer or second polymerizable compound(s) of the aqueous fluid. For example, the aqueous fluid may be an aqueous gel and the layer of the second polymeric material may be formed from the aqueous gel (see e.g., 104 in steps 2, 3, 4 of Fig. 1). In some embodiments, the first material is a non-polymeric material, such as those non-polymeric compounds described hereinabove. Features of the microneedle devices, such as the polymer or polymerizable compound(s), the second polymer or second polymerizable compound(s), and the base are as set out above. Thus, in certain embodiments, the first and second polymeric materials are independently selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethyl cellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methylcellulose, polyethylene glycol, gelatin and combinations thereof, for example the one or more polymeric powders are selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof. In some embodiments, the first and second polymeric materials may be the same and in other embodiments, the first and second polymeric materials may be different. In some embodiments, the microneedle device comprises one or more compounds of interest for administration into a biological tissue of a subject, and the one or more compounds of interest are optionally selected from ascorbic acid, salicylic acid, nicotinamide, hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid and combinations thereof. In certain embodiments, the layer of the second polymeric material has a thickness of between 0.1 pm and 1000 pm, such as between 1 pm and 500 pm, or between 0.1 pm and 100 pm, or between 5 pm and 20 pm. In some embodiments, the base has a thickness of between 5 to 10000 microns (pm), such as from 100 to 5000 microns (pm), or from 100 to 3000 microns (pm). In certain embodiments, the base is formed from a non-woven material, such as paper. In some embodiments, the base is formed from a polymer, such as polydimethylsiloxane (PDMS). Other Features Each and every compatible combination of the embodiments described above is explicitly disclosed herein, as if each and every combination was individually and explicitly recited. Various further aspects and embodiments of the invention will be apparent to those skilled in the art in view of the present disclosure. “and / or” where used herein is to be taken as specific disclosure of each of the two specified features or components with or without the other. For example, “A and / or B” is to be taken as specific disclosure of each of (i) A, (ii) B and (iii) A and B, just as if each is set out individually herein. Unless context dictates otherwise, the descriptions and definitions of the features set out above are not limited to any particular aspect or embodiment of the invention and apply equally to all aspects and embodiments which are described. Examples Certain aspects and embodiments of the invention will now be illustrated by way of example and with reference to the figures described above. Example 1 - Microneedle Device Preparation Microneedle devices according to the present invention were prepared using the following exemplary method. Preparation ofPDMS microneedle moulds. First, PDMS microneedle moulds were prepared by taking a preformed microneedle male master mould insert and covering the insert with degassed liquid polydimethylsiloxane (PDMS). The PDMS was then cured under ambient conditions (1 atmosphere and circa. 25 °C) before being removed from the preformed male master mould to form a female PDMS mould. The preformed microneedle male mould insert contained a 6x6 array of microneedle protrusions and was prepared using routine and well-known 2 photon polymerisation methodology that is commonly used to create such microneedle moulds. Moulds comprising different array sizes (e.g. other than 6x6) may also be used. Each microneedle female mould comprises microdepressions with a base diameter of 200 pm and a height of 400 pm. The microdepressions of the female mould thus have a volume of 0.01675 mm3. Filling the PDMS moulds Hyaluronic acid polymeric powder (PrincipHYAL Cube3 obtained from Infinity Ingredient and manufactured by ROELMIHPC) was then manually deposited onto the female moulds to completely cover the microdepressions in the moulds. Any excess polymeric powder was then removed from the surface of the moulds, with care taken not to disturb the powder located within the microdepressions. Once filled, each 6x6 array of microdepressions contained approximately 0.0014 g of hyaluronic acid polymeric powder. Therefore, each microneedle within the array contained approximately 0.0000389 g of hyaluronic acid polymeric powder. Preparing the aqueous fluid (polymeric gel) Next, a polymeric gel was prepared by using the following procedure. Cleaning the bottles: A 100 ml Pyrex bottle was washed by filling it with reverse osmosis (RO) water and then ultrasonicating in RO water for 3 minutes in the “degas” setting. Next, the bottle was ultrasonicated for 3 minutes using the “gentle” setting. Then, the bottle was rinsed with acetone before being rinsed again with RO water. Then, the bottle was placed an oven at 90 °C for 10 minutes to dry. Making the PVA polymer solution (polymeric gel): A lab oven was pre-heated to 90 °C. Next, a 100 ml volumetric cylinder was filled with required quantity of RO water (approximately 55 pS / cm) (using the following ratio of PVA to RO water: 20 g PVA: 20 ml RO Water). The RO water was then poured into a Pyrex bottle and the Pyrex bottle with the RO water was placed in the oven at 90 °C, with the cap on, for one hour. Next, Emprove Essential PVA 26-88 was weighed on a scale, in a polystyrene weighing dish. Emprove Essential PVA 4-88 could also be used. The Pyrex bottle was then removed from the oven and the weighed PVA was poured into the bottle before the cap was put back on. The sealed Pyrex bottle was then placed in the oven at 90 °C for 24 hours, before being placed on a rolling machine for continuous mixing. Preparing the backing layer Next, a pre-cut piece of backing material (cut into a 10mm diameter circle) was taken and a peppercorn sized drop of polymeric gel was placed on the centre of the backing material such that when aligned with the mould the area of gel covers all the exposed microneedle microdepressions. The backing material used was Cytiva Whatman Filter Paper Number 1, sourced from Sigma Aldrich. Adding the backing layer and compressing the filled microdepressions Next, the backing layer with added polymeric gel was aligned with the centre of the polymeric powder filled moulds (with the gel covered surface facing the powder filled microdepressions). The backing layer, once placed onto the filled microdepressions of the moulds, was then lightly pressed, before the moulds, gel and backing layer were placed underneath a 10 mm diameter compression probe. The filled moulds, gel and backing layer were then compressed to a peak force of 145 N and were held under this compression force for 30 seconds, during which any excess gel is forced out of the sides of the microneedle device assembly, leaving behind a thin and consistent gel film thickness (approximately 50 microns). The compression force was then removed, and the mould assemblies were moved to a storage area and left for 24 hours at ambient temperature and pressure (25 °C and 1 atmosphere). This step allowed the moisture from the polymeric gel to hydrate the polymeric powder, and subsequently cure the entire assembly. After standing for 24 hours, the microneedle device was removed from the PDMS mould by peeling it away from the mould insert. A picture of an exemplary microneedle device prepared according to the process of the present invention is shown in Figures 2 and 3. Example 2 - Microneedles Prepared by Hydration using Liquid Water Microneedles prepared by filling the microdepressions of a female microneedle mould with hyaluronic acid polymeric powder before hydrating said filled microdepressions with water were also prepared according to the following exemplary procedure. Preparation of PDMS microneedle moulds. Female PDMS moulds were prepared according to the same procedure described above in Example 1. Filling the PDMS moulds Hyaluronic acid polymeric powder (PrincipHYAL Cube3 obtained from Infinity Ingredient) was then manually deposited onto the mould to completely cover the microdepressions in the moulds. Any excess polymeric powder was then removed from the surface of the moulds, with care taken not to disturb the powder located within the microdepressions. Once filled, each 6x6 array of microdepressions contained approximately 0.0014 g of hyaluronic acid polymeric powder. Therefore, each microneedle within the array contained approximately 0.0000389 g of hyaluronic acid polymeric powder. A spherical droplet of RO water with an approximate diameter of 2 mm (giving an approximate volume of 33.5 mm3, which is approximately 0.034 millilitres) was then added to the top of the filled moulds. Adding the backing layer Next, a pre-cut piece of backing material (cut into a 10 mm diameter circle, Cytiva Whatman Filter Paper Number 1) was aligned with the centre of the polymeric powder filled moulds. The backing layer, once placed onto the filled microdepressions of the moulds, was then lightly pressed. The mould assemblies were then moved to a storage area and left for 24 hours at ambient temperature and pressure (25 °C and 1 atmosphere). This step allowed the water from droplet to permeate into the polymeric powder, and subsequently hydrate the entire assembly, prior to curing. After standing for 24 hours, the microneedles were removed from the PDMS mould by peeling it away from the mould insert. A picture of exemplary microneedles prepared according to the above process are shown in Figure 4. Example 3 - Microneedles Prepared by Hydration using Water Vapour Microneedles prepared by filling the microdepressions of a female microneedle mould with hyaluronic acid polymeric powder before exposing the filled microdeprerssions to humid conditions were also prepared according to the following exemplary procedure. Preparation of PDMS microneedle moulds. Female PDMS moulds were prepared according to the same procedure described above in Example 1. Filling the PDMS moulds Hyaluronic acid polymeric powder (PrincipHYAL Cube3 obtained from Infinity Ingredient) was then manually deposited onto the moulds to completely cover the microdepressions in the moulds. Any excess polymeric powder was then removed from the surface of the moulds, with care taken not to disturb the powder located within the microdepressions. Once filled, each 6x6 array of microdepressions contained approximately 0.0014 g of hyaluronic acid polymeric powder. Therefore, each microneedle within the array contained approximately 0.0000389 g of hyaluronic acid polymeric powder. The filled moulds were then compressed to a peak force of 145 N and was held under this compression force for 30 seconds. Humidity Hydration of the Filled Moulds Next, the filled and compressed moulds were placed in a chamber pre-conditioned to 95% relative humidity. The moulds were then left in the pre-conditioned chamber for 6 hours to absorb moisture (further tests were conducted leaving the moulds in the chamber for 1 and 24 hours). Next, the moulds were removed from the chamber and left to cure at 35 °C in a drying cabinet for 2 hours. Removing the microneedles from the mould Adhesive tape was then compressed onto the back of the filled moulds (at 145 N for 30 seconds). The adhesive tape was then peeled off the mould to extract the microneedles from the mould cavities. A picture of an exemplary microneedle device prepared according to the above process is shown in Figures 5 and 6. Alternatively, the filled moulds can have a polymeric gel (PVA gel as prepared above) applied to them as per the standard moulding method described above and left to cure. This allows cured microneedles to bond to the polymer gel layer, allowing the microneedles to be extracted from the mould as a single assembly. Examples 4 to 6- Microneedles Prepared from Magnesium Silicate, Magnesium Hydroxide and Corn Starch Microneedles prepared by fdling the microdepressions of a female microneedle mould with either magnesium silicate powder, magnesium hydroxide powder or com starch powder before hydrating said filled microdepressions with water were also prepared according to the following exemplary procedure. Preparation of PDMS microneedle moulds. Female PDMS moulds were prepared according to the same procedure described above in Example 1. Filling the PDMS moulds Magnesium Silicate powder (Sigma Aldrich, product code: 288705 - Example 4), Magnesium Hydroxide powder (Sigma Aldrich, product code: 63081- Example 5) or Com Starch powder (Sigma Aldrich, product code: S4180 - Example 6) was manually deposited onto the mould to completely cover the microdepressions in the moulds. Any excess powder was then removed from the surface of the moulds, with care taken not to disturb the powder located within the microdepressions. Once filled, each 6x6 array of microdepressions contained approximately 0.0014 g of powder. Therefore, each microneedle within the array contained approximately 0.0000389 g of the powdered compound. Preparing the aqueous fluid (polymeric gel) A polymeric gel was prepared using the same procedure described above in Example 1. Preparing the backing layer Backing material was prepared using the same procedure described above in Example 1. Adding the backing layer and compressing the filled microdepressions The backing layer with added polymeric gel was aligned and compressed according to the same procedure described above in Example 1. After standing for 24 hours, the microneedles were removed from the PDMS mould by peeling it away from the mould insert. A picture of exemplary microneedles prepared according to the above process are shown in Figures 7 to 9.

Claims

1. A process for preparing a microneedle device comprising: providing a mould having a plurality of microdepressions, each of which defines a microneedle;filling the microdepressions with a first dry material;exposing the filled microdepressions to an aqueous fluid and allowing the aqueous fluid to permeate through the filled microdepressions; and optionally curing the filled microdepressions.

2. The process according to claim 1, wherein the first dry material comprises one or more compounds of interest dispersed therein.

3. The process according to claim 1 or claim 2, wherein the first dry material comprises a polymer or polymerizable compounds.

4. The process according to claim 1 or claim 2, wherein the first dry material comprises a non-polymeric compound and, for example, is selected from charcoal, magnesium oxide, magnesium hydroxide, aluminium oxide, magnesium silicate, com starch and combinations thereof.

5. The process according to any one of claims 1 to 4, wherein the aqueous fluid is an aqueous gel comprising a second polymer or second polymerizable material, and wherein the second polymer or second polymerizable material may be the same and / or different to the polymer or polymerizable compounds of the first dry material.

6. The process according to claim 5, wherein the aqueous gel comprises between 40% and 99 % water based on the total weight of the gel, such as between 60% and 95% of water based on the total weight of the gel.

7. The process according to claim 5 or claim 6, wherein the second polymer is selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethylcellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methylcellulose, polyethylene glycol, gelatin and combinations thereof, such as hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof.

8. The process according to any one of claims 1 to 4, wherein the aqueous fluid comprises water vapour, and optionally comprises one or more other compounds (e.g. one or more oils).

9. The process according to any one of claims 1 to 8, wherein the process comprises a step of compressing the filled microdepressions before and / or after the step of exposing the filled microdepressions to an aqueous fluid.

10. The process according to claim 9, wherein the step of compressing the filled microdepressions is conducted using a force of at least 145 N, such as at least 160 N.

11. The process according to any one of claims 1 to 10, wherein the step of exposing the filled microdepressions to an aqueous fluid is conducted at a temperature of between 10 °C and 60 °C, such as between 15 °C and 50 °C, or between 20 °C and 40 °C.

12. The process according to any one of claims 1 to 11, wherein the first dry material has an average particle size of less than 100 pm, such as less than 50 pm, or less than 10 pm.

13. The process according to any one of claims 1 to 3 and 5 to 12, wherein the polymer is selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethyl cellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methylcellulose, polyethylene glycol, gelatin, polycaprolactone and combinations thereof, for example the polymer is selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof.

14. The process according to any one of claims 2 to 13, wherein the one or more compounds of interest are selected from ascorbic acid, salicylic acid, nicotinamide,hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid and combinations thereof.

15. The process according to any one of claims 1 to 15, wherein the method comprises a step of applying a base to the filled microdepressions.

16. A microneedle device prepared according to the process defined in any one of claims 2 to 15.

17. A microneedle device comprising: a base; andan array of microneedles, where the microneedles are formed from a first material; anda layer of a second polymeric material located between the base and the array of microneedles, such that the array of microneedles is located on one side of the layer of a second polymeric material and the base is located on the other side of the layer of a second polymeric material.

18. The microneedle device according to claim 17, wherein the microneedles are formed from a first polymeric material.

19. The microneedle device according to claim 17 or claim 18, wherein the layer of the second polymeric material has a thickness of between 0.1 pm and 1000 pm, such as between 1 pm and 500 pm, or between 1 pm and 100 pm, or between 5 pm and 20 pm.

20. The microneedle device according to any one of claims 17 to 19, wherein the first and second polymeric materials are independently selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol, carboxymethyl cellulose, polyvinylpyrrolidone, poly(lactic-co-glycolic acid), chitosan, hydroxypropyl methyl cellulose, polyethylene glycol, gelatin and combinations thereof, for example the first and second polymeric materials are selected from hyaluronic acid, sodium hyaluronate, polyvinyl alcohol and combinations thereof.

21. The microneedle device according to any one of claims 17 to 20, wherein at least one, such as each, microneedle comprises one or more compounds of interest for administration into a biological tissue of a subject, and the one or more compounds of interest are optionally selected from ascorbic acid, salicylic acid, nicotinamide, hydroquinone, retinol, glycolic acid, lactic acid, tartaric acid, citric acid and combinations thereof.

22. Use of a microneedle device according to any one of claims 16 to 21 for administration of one or more compounds of interest into a biological tissue of a subject.

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