Dissolving microneedles for the delivery of peptides - Towards tolerance-inducing vaccines.

Abstract Tolerance inducing vaccines have re-appeared in recent years as a mean to re-establish immunological tolerance in the context of autoimmune disease. In the case of multiple sclerosis, several myelin-related peptides have been identified. The use of microneedles (MNs) allows the painless administration of molecules to the epidermal and intradermal space. This approach has been considered particularly promising in the scope of vaccination as the skin represents an immunologically super-active organ. This work explores the preparation of a MN patch that can deliver immunologically active peptides foreseeing the establishment of tolerance in the context of multiple sclerosis. A new MN design was achieved by microfabrication. The patches are composed of a dense MN array containing 33 × 33 needles with 200 or 125 µm diameter and height around 600 µm. Polymeric MNs composed by poly(vinyl alcohol), poly(vinyl pyrrolidone) and chitosan were successfully obtained, replicating the silicon masters morphology. The polymer MN patches showed to perforate pig skin, reaching more than 400 µm depth of penetration when assessed using agarose as a model for the skin viscoelastic properties. The MNs with 200 µm diameter showed improved mechanical properties in comparison to 125 µm diameter MNs. The presence of chitosan in the MN structure was explored and found not to affect mechanical properties or significantly alter the drug loading or release profile. The immunomodulatory peptide associated with the proteolipid protein PLP139-151 was loaded in 200 µm diameter MN patch and it is released in physiological conditions at therapeutic doses of the peptide, putting forward this strategy to integrate a new tolerance-inducing therapy for multiple sclerosis successfully.