Process optimization of Ca2+ cross-linked alginate-based swellable microneedles for enhanced transdermal permeability: More applicable to acidic drugs

Abstract

We describe a swellable microneedle (SMN) consisting of Ca2+ cross-linked alginate, which expands the types of natural polymers available for SMN fabrication. After investigation of different fabrication methods, the alginate in situ hydrogel-based SMN with a flat substrate was successfully constructed, whose gelation was triggered by ethylenediaminetetraacetic acid calcium disodium salt and D-(+)-glucono-1,5-lactone. With the addition of polyvinyl alcohol and trehalose, SMN possessed good mechanical properties. The biocompatibility of SMN was demonstrated through the tests of in vitro cytotoxicity and in vivo skin irritation. With the assistance of SMN, the in vitro transdermal delivery efficiencies of drugs were significantly improved throughout 16 h. 3-O-ethyl ascorbic acid (EAA, pH = 4.81) exhibited a cumulative release of up to 83.83 ± 6.30%, which was consistent with zero-order kinetics, while tranexamic acid (TA, pH = 6.90) showed the most significant increase in delivery efficiency, which was consistent with the Higuchi model and Ritger-Peppas model. The SMN remained intact after the 16 h of EAA transdermal delivery, indicating its better suitability for acidic drugs. We believe that this technology has the potential to expand the range of drugs available for transdermal administration as well as the breadth of patient care applications.