This study investigates the feasibility of fabricating microneedles from triblock amphiphiles with linear poly(ethylene glycol) (PEG) as the hydrophilic middle block and two dendritic side-blocks with enzyme-cleavable hydrophobic end-groups. The addition of a sodium alginate base layer and different polymeric excipients was tested to enhance the mechanical strength of the microneedles. The optimized microneedles exhibited favorable insertion efficiency and low height reduction percentage when tested in a skin-simulant model. In buffer solution, the solid microneedles swelled into a hydrogel within about 30 seconds, followed by rapid disintegration into small hydrogel particles that could undergo slow enzymatic degradation to soluble polymers. In vitro release studies of dexamethasone (DEX) showed first-order drug release, with 90% released within 6 days. Ex vivo skin insertion tests using chicken skin demonstrated full penetration. This study demonstrates the potential of programming hydrogel-forming microneedles to undergo multiple mesophase transitions, offering a promising delivery system for self-administration, increased patient compliance, improved efficacy, and sustained drug release.This study investigates the feasibility of fabricating microneedles from triblock amphiphiles with linear poly(ethylene glycol) (PEG) as the hydrophilic middle block and two dendritic side-blocks with enzyme-cleavable hydrophobic end-groups. The addition of a sodium alginate base layer and different polymeric excipients was tested to enhance the mechanical strength of the microneedles. The optimized microneedles exhibited favorable insertion efficiency and low height reduction percentage when tested in a skin-simulant model. In buffer solution, the solid microneedles swelled into a hydrogel within about 30 seconds, followed by rapid disintegration into small hydrogel particles that could undergo slow enzymatic degradation to soluble polymers. In vitro release studies of dexamethasone (DEX) showed first-order drug release, with 90% released within 6 days. Ex vivo skin insertion tests using chicken skin demonstrated full penetration. This study demonstrates the potential of programming hydrogel-forming microneedles to undergo multiple mesophase transitions, offering a promising delivery system for self-administration, increased patient compliance, improved efficacy, and sustained drug release.