Rapid deamidation of recombinant protective antigen when adsorbed on aluminum hydroxide gel correlates with reduced potency of vaccine.

Deamidation of the recombinant protective antigen (rPA) correlates with decreased effectiveness of the vaccine in protecting against infection by Bacillus anthracis. We present data demonstrating dramatic deamidation of amino acid positions 713 and 719 of rPA adsorbed onto aluminum hydroxide gel, an adjuvant, relative to rPA stored in solution without adjuvant. Although deamidation did not impact total levels of rPA-specific antibodies in a mouse model, it did correlate with a decrease in toxin-neutralizing antibodies.

Evaluation of the effect of syringe surfaces on protein formulations.

Packaging of drugs in prefillable syringes offers considerable advantages over conventional vials. Almost all major biotech molecules are available on the market today in prefilled syringes, and are safe and efficacious. Newer high-concentration liquid formulations, especially fusion proteins, however, can suffer from instability in prefilled syringes due to syringe components like silicone oil.

Protective immunity in mice achieved with dry powder formulation and alternative delivery of plague F1-V vaccine.

The potential use of Yersinia pestis as a bioterror agent is a great concern. Development of a stable powder vaccine against Y. pestis and administration of the vaccine by minimally invasive methods could provide an alternative to the traditional liquid formulation and intramuscular injection.

Release from polymeric prodrugs: linkages and their degradation.

Polymeric prodrugs have evolved into a very useful class of drug delivery agents. Numerous polymeric prodrugs have been prepared for applications ranging from passive drug targeting to controlled release. The mechanistic aspects of the release processes, however, have not been clearly delineated.

Polyvinylpyrrolidone-drug conjugate: synthesis and release mechanism.

Covalent conjugates of polyvinylpyrrolidone (PVP) with para-nitroaniline (PNA) were synthesized as a model PVP-drug conjugate, and PNA release was evaluated in vitro. Pyrrolidone ring opening with subsequent t-BOC protection of the pyrrolidone nitrogen and reaction with PNA in methylene chloride (CH2Cl2) produced a PVP-PNA conjugate with 3% of the pyrrolidone groups modified. Rates of PNA release from N-deprotected conjugates were twofold greater than those that were N-protected, indicating participation of the pyrrolidone N in release.

Reaction of a peptide with polyvinylpyrrolidone in the solid state.

During stability studies at high temperature (70 degrees C) and low relative humidity ( approximately 0%), the recovery of an asparagine containing hexapeptide (VYPNGA) and its known deamidation products from solid polyvinylpyrrolidone (PVP) matrices was incomplete. To determine the causes of this mass loss, formulations were prepared by lyophilizing solutions containing PVP, glycerol, and the Asn-hexapeptide in pH 7.5 phosphate buffer, followed by storage at 70 degrees C and 0% relative humidity.