Publications, Pharmaceutical

Intranasal Delivery of Thin-Film Freeze-Dried Vaccine Powders

Intranasal vaccination via direct application of dry vaccine powder offers numerous advantages, but its successful implementation hinges on efficient transformation of a liquid vaccine into a dry powder and its subsequent delivery to the requisite nasal regions. In this research, a model vaccine comprising liposomal monophosphoryl lipid A, QS-21 adjuvant (AdjLMQ), and ovalbumin (OVA) as an antigen was examined. The liquid vaccine was successfully converted into a dry powder using thin-film freeze-drying, with the addition of sucrose at a 15:1 ratio with lipid, and optionally incorporating a mucoadhesive agent, carboxymethyl cellulose sodium salt (CMC).

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15 Jun 2023

The chosen model for further evaluation was the thin-film freeze-dried AdjLMQ/OVA vaccine powder containing 1.9% (w/w) of CMC, owing to its mucoadhesive qualities and ability to maintain antigen integrity and the vaccine’s physical properties. This powder displayed lower moisture content and higher glass transition temperature compared to versions without CMC. The resultant thin films also showed greater thickness.

Delivery of the dry vaccine powder was tested using Aptar Pharma’s Unidose Powder Nasal Spray System (UDSP), which displayed comparable results in particle size distribution, spray patterns, and plume geometries for both the CMC-containing and non-CMC vaccine powder. Importantly, the integrity of the OVA antigen and AdjLMQ liposomes was maintained post-spray using UDSP.

To optimize delivery parameters, a Taguchi L4 orthogonal array was used. This facilitated the identification of the best settings to target the middle and lower turbinate and nasopharynx regions in adult and child nasal replicas using the UDSP.

In conclusion, this study demonstrates the potential of thin-film freeze-drying technology for converting a nasal vaccine from a liquid to a dry powder. Furthermore, it confirms the capability of UDSP to effectively deliver the dry vaccine to the necessary regions for intranasal vaccination.

Read the Abstract on PubMed

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