A practical approach to the use of nanoparticles for vaccine delivery.
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 approximately 120 nm required higher surfactant concentration to resuspend postlyophilization than slightly larger ( approximately 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.
Wendorf
Janet
J
Novartis Vaccines and Diagnostics, Inc., 4560 Horton Street, Emeryville, California 94608, USA.
Singh
Manmohan
M
Chesko
James
J
Kazzaz
Jina
J
Soewanan
Elawati
E
Ugozzoli
Mildred
M
O'Hagan
Derek
D
D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D004338:Drug Combinations; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005260:Female; D005374:Filtration; D005612:Freeze Drying; D007074:Immunoglobulin G / Q000097:blood; D007510:Isatin / Q000031:analogs & derivatives / Q000737:chemistry; D008353:Mannitol / Q000737:chemistry; D022401:Meningococcal Vaccines / Q000008:administration & dosage*; D051379:Mice; D008815:Mice, Inbred Strains; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry; D011098:Polyglactin 910 / Q000737:chemistry; D011142:Polyvinyl Alcohol / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D012710:Serum Albumin, Bovine / Q000737:chemistry; D013386:Succinates / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D014199:Trehalose / Q000737:chemistry
D001426:Bacterial Proteins; D004338:Drug Combinations; D005079:Excipients; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D011725:Pyridines; D013386:Succinates; D013501:Surface-Active Agents; C001526:laxagetten 4,4'-diacetoxydiphenylpyridylemethane; D012710:Serum Albumin, Bovine; D011098:Polyglactin 910; D008353:Mannitol; D007510:Isatin; D011142:Polyvinyl Alcohol; D010047:Ovalbumin; D014199:Trehalose