Polymer reinforced carbon nanotube micro needles fabrication for transdermal drug delivery

The subcutaneous injection is a more preferred method in desease treatments since oral administration of drugs is not feasible because of poor drug absorption or enzymatic degradation in the gastrointestinal tract or liver. However, it is seen that this method is also inadequate in some aspects beacause of issues emerged in its practice and use of high dose madications to be effected. For these reasons, the subcutaneous injection carried out by hypodermic needles is about to yield next generation drug delivery methods. The transcutaneous delivery by microneedle (MN) injection is the foremost among these methods. Among all concerns associated with the subcutaneous injection, pain caused by a needle insertion, bleeding and deformation in the applied region, and as a result needlephobia and anxiety in patients are prominents. On the other hand, MNs facilitate transdermal delivery without pain, bleeding and deformation since their size is so small, thus being applied without stimulating fear and anxiety. Morever, since MN application is very practical, it can be self-administred by patient itself without required technical skill, thus preventing accidental needle stuck injuries occurred in use of hypodermic needles. The skin targeted by MN injection is a residence of wealthy antigen presenting cells. Langerhans cells are abundant in the epidermis while dendritic cells are found in the dermis. Therefore, targeting the skin with MN injection increases efficient use of drugs and enables significant dose sparing compared to the subcutaneous or intramascular injection by hypodermic needles. MN types of various functionalities have been fabricated by many researchers using various materials and fabrication techniques so that MN mediated drug delivery, which has a great potential, is widely used. The applicability and success of the MN mediated drug delivery largely depend on the simplicity of the fabrication and functionalities of MNs. Therefore, choosing a material which provides convenience in fabrication and structural flexibility to manufacturer has a great importance. The selection of building materials of MNs as a silicon or metals increases the number of processing steps in the fabrication and the production time and cost. Besides, bottom-up approach allows more scalable and flexible fabrication to create structures of MNs compared to top-down approach. In this respect, carbon nanotube (CNT) looks an ideal material in MN fabrication when the simplicity and flexibility of its synthesis are considered. The capability to form the entire geometry of the MN, including the lumen, with a single step of CNT synthesis considerably facilitetes the fabrication. Based on the literature searches, it has been seen that CNT based MN fabrication was reported by only one group while silicon, metal, glass and polymer based MN fabrications have been reported so many times by many groups. In the reported study of CNT based MN fabrication, the number of MNs in a single array is just 9 and it is considered that the drug delivery via this limited number of channels takes long time. Moreover, it has been reported many times that the flow rate, from drug delivery tests, is significantly slowed down by the skin compression to the tip of hollow MNs. Some solutions to this problem, such as partial retraction of the MN and designing a beveled MN tip, have been recomended. But, since the length of MNs are very short, partial retraction may not be carried out practically. For these reasons, the aim of this proposed project is fabrication of an array of hollow MNs for transdermal drug delivery using vertically aligned CNTs, reinforced with a polymer and designed with a novel head preventing the skin compression, and to test their robustness and fluid flow rate. In the proposed project, vertically grown CNTs by chemical vapor deposition (CVD) method will form the scaffold of the hollow MNs. Fe nanoparticles which catalyze CNT synthesis will be patterned on SiO2 as hollow circles by using photolitography and electron beam evaporation technique, thus CNTs will grow up from only these regions. As a result, vertically grown CNT bundle will have the shape of hollow, cylindrical MNs. The vertically alligned CNT scaffold has a porous structure which has less strength against physical pressures. To overcome the issue and provide a mechanical strength, the pourus scaffold will be filled with polyethylene glycol diacrylate (PEGDA) polymer by using spin coater. The CNT MNs reinforced with PEGDA will reach the mechanical strength in order to penetrate the outermost layer of the skin (stratum corneum). Each individual CNT in the bundle will be functionalized by chemical bonds formed between PEGDA and CNTs. Hence, the controversial toxicitiy of unfunctionalized CNTs in the literature will be eleminated by coating with biocompatible PEGDA. The remaining polymer will pour on SiO2 and will form a polymer layer which will mechanically support the array of CNT MNs from the bottom and will help to separate it from SiO2 surface. It is possiple to fabricate the various sizes of CNT MNs by changing the litography and synthesis parameters. This allows to fabricate MNs with different heights and diameters. The head of the CNT MN, thought to prevent the skin compression, will aslo be formed during the CNT synthesis thanks to a catalyst patterning and litography. The number of CNT MNs in a single array is considered as at least between 25-100 in order to increase the fluid flow rate. Therefore, we are planning to improve the flow rate in the reported CNT MN study in the literature for between 3-10 fold. After the CNT synthesis and polymer contribution, in order to facilitate its application, MN array will be attached to an apparatus made from polydimethylsiloxane (PDMS). Thanks to this apparatus, CNT MNs can be used by attaching to a syringe or a thin silicon tubing. The mechanical strength and fluid flow rate of CNT MNs will be tested in hydrogel and in cadaver rat skin (in vitro). Before and after the application, CNT MNs will be viewed by SEM to check its strength and whether its structure would be damaged. With the successful completion of the proposed project, an alternative MN which provides simple, scalable and low cost fabrication, as well as painless, bloodles and high flow rate transdermal drug delivery will be developed. When the advantages in the CNT MN fabrication are considered, it is seen that CNT MNs have a high potential to find a chance in application.