title: Formulations for microprojection/microneedle vaccine delivery: Structure, strength and release profiles.
abstract: To develop novel methods for vaccine delivery, the skin is viewed as a high potential target, due to the abundance of immune cells that reside therein. One method, the use of dissolving microneedle technologies, has the potential to achieve this, with a range of formulations now being employed. Within this paper we assemble a range of methods (including FT-FIR using synchrotron radiation, nanoindentation and skin delivery assays) to systematically examine the effect of key bulking agents/excipients - sugars/polyols - on the material form, structure, strength, failure properties, diffusion and dissolution for dissolving microdevices. We investigated concentrations of mannitol, sucrose, trehalose and sorbitol from 1:1 to 30:1 with carboxymethylcellulose (CMC), although mannitol did not form our micro-structures so was discounted early in the study. The other formulations showed a variety of crystalline (sorbitol) and amorphous (sucrose, trehalose) structures, when investigated using Fourier transform far infra-red (FT-FIR) with synchrotron radiation. The crystalline structures had a higher elastic modulus than the amorphous formulations (8-12GPa compared to 0.05-11GPa), with sorbitol formulations showing a bimodal distribution of results including both amorphous and crystalline behaviour. In skin, diffusion properties were similar among all formulations with dissolution occurring within 5s for our small projection array structures (~100μm in length). Overall, slight variations in formulation can significantly change the ability of our projections to perform their required function, making the choice of bulking/vaccine stabilising agents of great importance for these devices.
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, QLD 4072, Australia.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Raphael
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, QLD 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Crichton
authors.affiliation: University of Sheffield, Department of Chemical & Biological Engineering, ChELSI Institute, Sheffield S1 3JD, England, United Kingdom.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Falconer
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, QLD 4072, Australia.
authors.forename: Stefano
authors.initials: S
authors.lastname: Meliga
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, QLD 4072, Australia.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, QLD 4072, Australia.
authors.forename: Germain J P
authors.initials: GJ
authors.lastname: Fernando
authors.affiliation: The University of Queensland, School of Mechanical and Mining Engineering, QLD 4072, Australia.
authors.forename: Han
authors.initials: H
authors.lastname: Huang
authors.affiliation: The University of Queensland, Delivery of Drugs and Genes Group (D(2)G(2)), Australian Institute for Bioengineering and Nanotechnology, QLD 4072, Australia; ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, Australia; The University of Queensland, Faculty of Medicine and Biomedical Sciences, Royal Brisbane and Women's Hospital, Herston, Queensland 4006, Australia. Electronic address: m.kendall@uq.edu.au.
authors.forename: Mark A F
authors.initials: MA
authors.lastname: Kendall
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003911:Dextrans / Q000008:administration & dosage / Q000737:chemistry; D065546:Drug Liberation; D005079:Excipients / Q000008:administration & dosage / Q000737:chemistry*; D005260:Female; D008353:Mannitol / Q000008:administration & dosage / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008845:Microinjections; D009339:Needles; D010047:Ovalbumin / Q000008:administration & dosage / Q000737:chemistry; D012235:Rhodamines / Q000008:administration & dosage / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D013395:Sucrose / Q000008:administration & dosage / Q000737:chemistry; D014199:Trehalose / Q000008:administration & dosage / Q000737:chemistry; D014612:Vaccines / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D003911:Dextrans; D005079:Excipients; D012235:Rhodamines; D014612:Vaccines; C051311:rhodamine dextran; D008353:Mannitol; D013395:Sucrose; D010047:Ovalbumin; D014199:Trehalose; D002266:Carboxymethylcellulose Sodium
keywords: Drug delivery; Formulation; Microneedles; Skin; Vaccine