Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive vaccine powders

Yu-Sheng Yu; Khaled AboulFotouh; Haiyue Xu; Gerallt Williams; Julie Suman; Chris Cano; Zachary N Warnken; Kevin C-W Wu; Robert O Williams 3rd; Zhengrong Cui

doi:10.1016/j.ijpharm.2023.122990

Feasibility of intranasal delivery of thin-film freeze-dried, mucoadhesive vaccine powders

Int J Pharm. 2023 Jun 10:640:122990. doi: 10.1016/j.ijpharm.2023.122990. Epub 2023 Apr 29.

Authors

Affiliations

¹ The University of Texas at Austin, College of Pharmacy, Division of Molecular Pharmaceutics and Drug Delivery, Austin, TX, United States; National Taiwan University, Department of Chemical Engineering, Taipei, Taiwan.
² The University of Texas at Austin, College of Pharmacy, Division of Molecular Pharmaceutics and Drug Delivery, Austin, TX, United States.
³ Aptar Pharma, Le Vaudreuil, France.
⁴ Aptar Pharma, Congers, NY, United States.
⁵ TFF Pharmaceuticals, Inc., Fort Worth, TX, United States.
⁶ Via Therapeutics, Inc., Austin, TX, United States.
⁷ National Taiwan University, Department of Chemical Engineering, Taipei, Taiwan; National Health Research Institute, Institute of Biomedical Engineering and Nanomedicine, Miaoli, Taiwan.
⁸ The University of Texas at Austin, College of Pharmacy, Division of Molecular Pharmaceutics and Drug Delivery, Austin, TX, United States. Electronic address: Zhengrong.cui@austin.utexas.edu.

PMID: 37127138
DOI: 10.1016/j.ijpharm.2023.122990

Abstract

Intranasal vaccination by directly applying a vaccine dry powder is appealing. However, a method that can be used to transform a vaccine from a liquid to a dry powder and a device that can be used to administer the powder to the desired region(s) of the nasal cavity are critical for successful intranasal vaccination. In the present study, using a model vaccine that contains liposomal monophosphoryl lipid A and QS-21 adjuvant (AdjLMQ) and ovalbumin (OVA) as a model antigen, it was shown that thin-film freeze-drying can be applied to convert the liquid vaccine containing sucrose at a sucrose to lipid ratio of 15:1 (w/w) into dry powders, in the presence or absence of carboxymethyl cellulose sodium salt (CMC) as a mucoadhesive agent. Ultimately, the thin-film freeze-dried AdjLMQ/OVA vaccine powder containing 1.9% (w/w) of CMC (i.e., TFF AdjLMQ/OVA/CMC_1.9% powder) was selected for additional evaluation because the TFF AdjLMQ/OVA/CMC_1.9% powder was mucoadhesive and maintained the integrity of the antigen and the physical properties of the vaccine. Compared to the TFF AdjLMQ/OVA powder that did not contain CMC, the TFF AdjLMQ/OVA/CMC_1.9% powder had a lower moisture content and a higher glass transition temperature. In addition, the TFF AdjLMQ/OVA/CMC_1.9% thin films were relatively thicker than the TFF AdjLMQ/OVA thin films without CMC. When sprayed with Aptar Pharma's Unidose Powder Nasal Spray System (UDSP), the TFF AdjLMQ/OVA powder and the TFF AdjLMQ/OVA/CMC_1.9% powder generated similar particle size distribution curves, spray patterns, and plume geometries. Importantly, after the TFF AdjLMQ/OVA/CMC_1.9% powder was sprayed with the UDSP nasal device, the integrity of the OVA antigen and the AdjLMQ liposomes did not change. Finally, a Taguchi L4 orthogonal array was applied to identify the optimal parameters for using the UDSP device to deliver the TFF AdjLMQ/OVA/CMC_1.9% powder to the middle and lower turbinate and the nasopharynx regions in both adult and child nasal replica casts. Results from this study showed that it is feasible to apply the thin-film freeze-drying technology to transform a nasal vaccine candidate from liquid to a dry powder and then use the UDSP nasal device to deliver the vaccine powder to the desired regions in the nasal cavity for intranasal vaccination.

Keywords: Adult; Freeze-drying; Nasal; Pediatric; Powder; Vaccine.

MeSH terms

Administration, Intranasal
Antigens
Child
Feasibility Studies
Freeze Drying
Humans
Ovalbumin
Particle Size
Powders
Vaccination
Vaccines*

Substances

Powders
Vaccines
Antigens
Ovalbumin