Acid-Treated Water-Soluble Chitosan Suitable for Microneedle-Assisted Intracutaneous Drug Delivery

Abstract

Chitosan has been widely used as a nature-derived polymeric biomaterial due to its high biocompatibility and abundance. However, poor solubility in aqueous solutions of neutral pH and multiple fabrication steps for the molding process limit its application to microneedle technology as a drug delivery carrier. Here, we present a facile method to prepare water-soluble chitosan and its application for sustained transdermal drug delivery. The water-soluble chitosan was prepared by acid hydrolysis using trifluoroacetic acid followed by dialysis in 0.1 M NaCl solutions. We successfully fabricated bullet-shaped microneedle (MN) arrays by the single molding process with neutral aqueous chitosan solutions (pH 6.0). The chitosan MN showed sufficient mechanical properties for skin insertion and, interestingly, exhibited slow dissolving behavior in wet conditions, possibly resulting from a physical crosslinking of chitosan chains. Chitosan MN patches loading rhodamine B, a model hydrophilic drug, showed prolonged release kinetics in the course of the dissolving process for more than 72 h and they were found to be biocompatible to use. Since the water-soluble chitosan can be used for MN fabrication in the mild conditions (neutral pH and 25 °C) required for the loading of bioactive agents such as proteins and achieve a prolonged release, this biocompatible chitosan MN would be suitable for sustained transdermal drug delivery of a diverse range of drugs.

High Substitution Synthesis of Carboxymethyl Chitosan for Properties Improvement of Carboxymethyl Chitosan Films Depending on Particle Sizes

“…Chitosan is obtained by the deacetylation of chitin, for which the abundant renewable sources are the shells of crustaceans and mollusks [ 3 , 9 ]. However, chitosan is insoluble in neutral water (pH ~7) owing to the presence of amino groups (–NH 2 ) in the chitosan, in which this functional group remains unprotonated in neutral water [ 10 ]. Therefore, an improvement of water solubility of chitosan is required prior to its application.…”

Microneedle-Based Natural Polysaccharide for Drug Delivery Systems (DDS): Progress and Challenges

“…Water-soluble chitosan is also prepared by treatment of trifluoroacetic acid followed by a 0.1 M NaCl solution. This method was found to be suitable for sustained transdermal drug delivery of more than 72 h [131].…”

Translation of Polymeric Microneedles for Treatment of Human Diseases: Recent Trends, Progress, and Challenges

“…Droplet-born air blowing (DAB) is a novel technique of fabrication where the droplet of a polymer is shaped into the MN through air blowing [ 70 ], as shown in Figure 8 . The direct application of the air is for the solidification of the polymer droplet that helps in the formation of the shape of the MN [ 151 ]. This DAB technology allows the fabrication under conditions without the need for UV irradiation or high heat [ 152 ].…”