A practical approach to the use of nanoparticles for vaccine delivery - Surfactants

A practical approach to the use of nanoparticles for vaccine delivery
Received: 27 February 2006; Revised: 15 July 2006; Accepted: 19 July 2006
Published Online: 21 Aug 2006
Janet Wendorf, Manmohan Singh, James Chesko, Jina Kazzaz, Elawati Soewanan, Mildred Ugozzoli, Derek O'Hagan *
Journal of Pharmaceutical Sciences
Wiley InterScience
Copyright ? 2006 Wiley-Liss, Inc.
Novartis Vaccines and Diagnostics, Inc., 4560 Horton Street, Emeryville, California 94608

email: Derek O'Hagan (derek_ohagan@chiron.com)
*Correspondence to Derek O'Hagan, Novartis Vaccines and Diagnostics, Inc., 4560 Horton Street, Emeryville, California 94608. Tel-510-923-7662; Fax-510-923-2586.
Keywords
nanoparticles ? microparticles ? vaccine delivery ? vaccine adjuvants ? lyophilization
Abstract
The objective of this work was to obtain a nanoparticle formulation that could be sterile filtered, lyophilized, and resuspended to the initial size with excipients appropriate for use as a vaccine formulation. Poly(lactide-co-glycolide) (PLG) polymers were used to create nanoparticles ranging in size from 110 to 230 nm. Protein antigens were adsorbed to the particles; the protein-nanoparticles were then lyophilized with the excipients. Vaccine compatible excipient combinations of sugars alone, surfactants alone, and sugars and surfactants were tested to find conditions where initial particle size was recovered. Sterile filtration of smaller nanoparticles led to minimal PLG losses and allowed the particle preparation to be a nonaseptic process. We found that the smaller nanoparticles of size 120 nm required higher surfactant concentration to resuspend postlyophilization than slightly larger (220 nm) particles. To resuspend 120 nm nanoparticles formulations of poly(vinyl alcohol) (PVA) with sucrose/mannitol or dioctyl sodium sulfosuccinate (DSS) with trehalose/mannitol were sufficient. The protein-nanoparticles resuspension with the same excipients was dependent on the protein and protein loading level. The nanoparticle formulations in vivo were either similar or had enhanced immunogenicity compared to aluminum hydroxide formulations. A lyophilized nanoparticle formulation with adsorbed protein antigen and minimal excipients is an effective vaccine delivery system. Copyright ? 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2738-2750, 2006
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