Delivery of allergen powder for safe and effective epicutaneous immunotherapy

Abstract

Background: More effective and safer immunotherapies to manage peanut allergy are in great demand despite extensive investigation of sublingual/oral immunotherapy and epicutaneous immunotherapy (EPIT) currently in the clinics. Objective: We sought to develop a powder-laden, dissolvable microneedle array (PLD-MNA) for epidermal delivery of powdered allergens and to evaluate the efficacy of this novel EPIT in peanut-sensitized mice. Methods: PLD-MNA was packaged with a mixture of powdered peanut allergen (PNA), 1,25-dihydroxyvitamin D 3 (VD3), and CpG. Its epidermal delivery and therapeutic efficacy were evaluated alongside PNA-specific forkhead box P3-positive regulatory T cells and IL-10 1 and TGF-b1 1 skin-resident macrophages. Results: PLD-MNA was successfully laden with PNA/VD3/CpG powder and capable of epidermal delivery of most of its content 1 hour after application onto intact mouse skin concomitant with no significant leakage into the circulation or skin irritation. PLD-MNA-mediated EPIT substantially reduced clinical allergy scores to 1 from 3.5 in sham control mice (P < .001) after 6 treatments accompanied by lower levels of PNA-specific IgE and intestinal mucosal mast cells and

Monoolein Assisted Oil-Based Transdermal Delivery of Powder Vaccine

“…Compared with the PBS-based patch, the oil-based patch could deliver more OVA into the skin. Confocal images showed that OVA had reached the interior of some cells, which had corresponding sizes and shapes to the APCs shown in a previous report [ 21 ]. In the images of skin sections, OVA was mainly found in the SC, and a smaller amount was found around hair follicles and in the upper dermis.…”

“…At an MO concentration of 3% w / w and at 24 h of incubation, the proteins were not detected in the receptor medium; however, this is preferable in some cases such as antigen immunotherapy. In epicutaneous antigen immunotherapy, antigens are delivered only to the epidermis and are inhibited from entry to the dermis to prevent antigen delivery to the systemic circulation and thereby avoid acute severe immune reactions [ 21 , 22 ].…”

“…Unfortunately, APCs were not confirmed in the immunostained sections (data not shown). In a previous study using mice that secrete MHC II fused with enhanced green fluorescent protein, APCs assembled around OVA delivered using microneedles after 24 h [ 21 ]. Thereafter, APCs eventually migrated into the subcutaneous tissues over several days.…”

“…The crystal reservoir technology employed in the tulobuterol patch (Hokunalin Tape) enables sustained drug release at a constant level, using a mixture of dissolved tulobuterol and tulobuterol crystals [ 19 ]. In other studies, powder proteins and antigens were dispersed in a deep eutectic solvent [ 20 ], and loaded in a dissolving microneedle [ 21 ], or deposited on an occlusive patch [ 21 ]. The Viaskin occlusive patch utilizes sweat and water vapor from the skin, and antigens deposited on patches dissolve into this moisture, and permeate through the SC [ 22 ].…”

Molecular approaches to allergen‐specific immunotherapy: Are we so far from clinical implementation?

“…A novel EPIT based on dissolvable microneedle array (PLD‐MNA) coated with powdered peanut allergens mixed with 1,25‐dihydroxyvitamin D3 and CpG adjuvants (See Chapter 9) was recently evaluated for the treatment of peanut allergy in preclinical studies . Compared with intradermal EPIT, PLD‐MNA EPIT did not provoke any local skin inflammation.…”