Electrophoretic Deposition of Chitosan/Clobetasol Propionate Composite Micro-Pattern Scaffolds: Fabrication Process and Material Properties

Abstract

Introduction: Electrophoretic deposition (EPD) is an efficient bottom-up technology that enables the fabrication of self-standing structures based on biopolymers. Thin or thick films, deposited on patterned working electrodes, replicate, under suitable processing parameters, the substrate morphology: by peeling them off the substrates, structures with controlled three-dimensional morphologies can be obtained. Moreover, the mild EPD conditions allow to process sensitive organic molecules, such as drugs, without impairing their structure and activity. In this work we used EPD-based replica technique in order to design Chitosan strips which are loaded with specific amount of Clobetasol propionate, in order to design with a one-pot approach drug delivery systems for topical oral administration. Materials and Methods: Titanium cathode substrates (Ti, grade 2) were patterned via mechanical micro-drilling of regular square lattices of rectangular holes (F = 500-1000 mm, distance = 100-500 mm). Processing conditions have been optimized in order to reproduce the patterns: square waves (75-100 V, duty cycle = 20 min.) have been used in 30% water + 70% ethanol bath (pH~5.0, [Chitosan] = 1gr L-1, [Clobetasol] = 12.5 mg L-1). Obtained films were mechanically removed after freeze-drying. Specimens were further crosslinked (1% w/w Genipin solution (5mg L-1 in ethanol)) in order to modulate their overall behavior. Obtained specimens were characterized in terms of mechanical, water uptake in different environments (PBS, acidic and alkaline solutions), morphology properties, and drug delivery. Results and discussion: Optimum conditions to modulate both thickness and morphology of chitosan strips were determined by investigating the effects of the initial pH, ethanol/water bath concentration, and EPD processing parameters. A uniform distribution of pores and a precise replica of the shape of the pattern has been obtained. In order to study the presence of Clobetasol propionate in Chitosan strips, the fabricated materials were re-dissolved in acidic water/ethanol solutions and evaluated by spectrophotometer(Figure 1): the effective incorporation of drug has been tuned by adjusting the starting EPD solutions Chitosan/Clobetasol propionate composite structure showed different behaviors as a consequence of both morphology and microstructure in both water uptake and tensile properties. The cross-linked scaffolds show lower strain at break with a higher Young’s modulus, compared to the noncross-linked ones. They also showed a less degree of swelling (165%-330%) relative to the non-cross-linked ones (240%-370%). Conclusion: EPD has been exploited as a powerful technique to precise replicate micro-patterned substrates and to effectively incorporate drugs in a one-pot approach. Properties of obtained structures can be further modulated in order to design a family of biopolymers based structures that can be advantageously used in different topical drug delivery applications. Figure 1