Esposito, Eliana (2014) ELECTRO-DRAWN POLYMER MICRONEEDLES FOR TRANSDERMIC DELIVERY OF LIPOPHILIC AND HYDROPHILIC COMPOUNDS. [Tesi di dottorato]

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Transdermic drug delivery is emerging more and more since it overcomes some disadvantages of classical route of administration. Indeed, kinetics of delivery can be controlled, avoiding bolus release, and environment in which drugs diffuse is safer way than gastro-intestinal tract. The systems currently used for transdermic delivery, like electroporation, iontophoresis and penetration enhancers, are very complex and relatively dangerous for patient. These systems destabilize the structure of stratum corneum to increase skin permeability, or using chemical substances that interact with lipids, or through the passage of electrical currents in the skin. By using patches with microneedles, it has been proved that it is possible to solve mechanically problems related to the permeability of the stratum corneum, also for molecules with large size; indeed, microneedles create micro holes in skin, without destabilizing chemically its structure. By various research groups both metallic and polymeric microneedles have been manufactured, using different techniques of production. Polymeric biodegradable microneedles allow obtaining a better control of kinetics release and to load an higher drug’s amount. The purpose of this work was to develop a new manufacturing technique which overcomes the constraints of the techniques already used, preserving the effectiveness of the final device obtained. The new method exploits the electric field, generated by a pyroelectric crystal, for the formation, through the drawing of a polymer solution, of micro conical tips able to cross the stratum corneum. The entire production process takes a few minutes at mild temperatures, without creating any contact between the polymeric solution and other things that may be contaminated. The shaping effect of the electric field can be run on both simple polymer solutions (PLGA in dimethyl carbonate) and on water in oil emulsions. In the latter case it was possible to load both hydrophobic compounds in the polymer matrix, and hydrophilic molecules in the aqueous phase emulsified in the polymer solution. To limit the presence of drug only in the cone and minimize wastage of active compounds, it was used a double drop deposition. It means that a drop of simple solution of PLGA is used like base, and then a smaller drop loaded with drug is deposited on it. Another important objective of this project was the manipulation microneedles morphology. To produce several degrees of porosity in the polymeric matrix, it was changed the water content in the emulsion. By increasing water phase, it was possible to obtain higher release rates and degradation of PLGA matrix. However, the maximum amount of water is limited by mechanical properties: microneedles have to preserve enough resistance to indent the skin.

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