The purpose of this study was to develop a spray‐freeze‐drying (SFD) process for preparing an influenza vaccine dry powder formulation suitable for epidermal powder immunization. After preformulation of two types of flu vaccines, their dry‐powder formulations were prepared by SFD. Powder properties and physical stability were determined using particle size analysis, tap density measurement, scanning electron microscopy, optical microscopy, and moisture content analysis. Chemical and biochemical stability of vaccine antigens was determined by sodium dodecyl sulfate–polyacrylamide gel electrophoresis, single radial immunodiffusion assay, and in vivo immunogenicity in a mouse model. We demonstrated that SFD could produce high‐density particles—a critical parameter for effective skin penetration. From the stability perspective, the stress posed by SFD was mild because the antigen in the dry powder retained its stability, potency, and immunogenicity. Among several formulations screened, we noted that formulation composition has a significant role in the powder's long‐term physical and biochemical stability. One formulation, in particular, containing sub‐unit vaccine (45 μg of antigen in 1 mg of powder) with a tertiary mixture of trehalose, mannitol, and dextran, exhibited excellent overall stability, including acceptable biochemical stability after being exposed to a highly humid environment. After all, we have not only demonstrated the suitability of SFD to prepare powders for epidermal powder immunization but also developed a systematic formulation development strategy that allowed the optimization of an influenza vaccine dry powder formulation. More important, this study led to the selection of a formulation system that had been successfully tested in a human clinical study. © 2004 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 93:1912–1923, 2004
Epidermal powder immunization (EPI) with an influenza vaccine and an adjuvant such as QS-21, LTR72, or cholera toxin elicited augmented serum and mucosal antibody responses in mice. Rhesus macaques, which have an immune system and skin structure similar to humans, were used to further evaluate the immunogenicity of the influenza vaccine following EPI. EPI of rhesus macaques with an influenza vaccine and QS-21 adjuvant elicited significantly higher serum hemagglutination inhibition (HI) titers than antigen alone administered by EPI or by intramuscular (IM) injection using a needle and syringe. In the absence of QS-21, EPI and IM injection elicited comparable HI titers in the monkeys. This study suggests that EPI is a promising technique for administering human vaccine and that QS-21 augments the immunogenicity of co-administered influenza vaccine.
The recombinant envelope gp120 (rgp120) of human immunodeficiency virus (HIV) is a weak immunogen when administered by intramuscular (IM) injection. In the present study, we report that epidermal powder immunization (EPI) elicits robust antibody responses to the rgp120. EPI of mice with a dose 0.2-5 microg of rgp120 protein elicited geometric mean antibody titers that were 18- to 240-fold higher than that elicited by IM injection using a 5.0 microg dose. Targeting antigen to and mobilization of Langerhans cells (LCs) by EPI may explain the enhanced immunogenicity of the rgp120. EPI with rgp120 using sugar and gold particles as carrier resulted in differential antigen entry into the LCs and differential IgG subclass antibody and cellular immune responses. EPI may serve as a useful tool to evaluate vaccine potential of the rgp120 protein.
The skin is an immunologically active site and an attractive vaccination route. All current vaccines, however, are administered either orally, intramuscularly, or subcutaneously. We previously reported that epidermal powder immunization (EPI) with an extremely small dose of powdered influenza vaccine induces protective immunity in mice. In this study, we report that commonly used adjuvants can be used in EPI to further enhance the immune responses to an antigen. The IgG antibody response to diphtheria toxoid (DT) following EPI was augmented by 25- and 250-fold, when 1 microg DT was co-delivered with aluminum phosphate (alum) and a synthetic oligonucleotide containing CpG DNA motifs (CpG DNA), respectively. These antibodies had toxin-neutralization activity and were long lasting. Furthermore, EPI using an adjuvant selectively activated different subsets of T helper cells and gave either a Th1 or a Th2 type of immune response. Similar to needle injection into deeper tissues, EPI with alum adsorbed DT promoted a predominantly IgG1 subclass antibody response and elevated level of IL-4 secreting cells. These are indicative of Th2-type immunity. In contrast, co-delivery of CpG DNA adjuvant via EPI led to Th-1 type of response as characterized by the increased production of IgG2a antibodies and IFN-gamma secreting cells. This study indicated that EPI using appropriate adjuvants can produce an augmented antibody response and desirable cellular immune responses. EPI is a promising immunization method that may be used to administer a broad range of vaccines including vaccines with adjuvants.
Esterification de poly (acide acrylique) et de poly (acide methacrylique) par des halogenures d'alkyl encombres via leurs sels de tetrabutylammonium correspondants selon 3 approches differentes. Influence de l'eau presente dans le milieu sur le rendement de la reaction. Obtention de polymeres cristaux liquides ayant un degre de substitution superieur a 25% pour le polyacrylate et a 40% pour le methacrylate
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTThe preparation of liquid-crystalline side-chain polyacrylate by chemically modifying poly(sodium acrylate) in hexamethylphosphoramideS. H. Chen and Y. F. MaaCite this: Macromolecules 1988, 21, 9, 2697–2699Publication Date (Print):September 1, 1988Publication History Published online1 May 2002Published inissue 1 September 1988https://pubs.acs.org/doi/10.1021/ma00187a008https://doi.org/10.1021/ma00187a008research-articleACS PublicationsRequest reuse permissionsArticle Views108Altmetric-Citations-LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTA reexamination of the synthesis of liquid crystalline side-chain polyacrylates via liquid-liquid phase-transfer catalysisS. H. Chen and Y. F. MaaCite this: Macromolecules 1988, 21, 4, 904–907Publication Date (Print):April 1, 1988Publication History Published online1 May 2002Published inissue 1 April 1988https://doi.org/10.1021/ma00182a009RIGHTS & PERMISSIONSArticle Views42Altmetric-Citations8LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (497 KB) Get e-Alerts Get e-Alerts
The microcalorimetrically determined heat of dilution data are used to evaluate the enthalpy of micellization at the CMC (ΔHM) for potassium decanoate in H2O and D2O. The values for ΔHM based on a mass-action model are in good agreement with those determined graphically. That ΔHM in D2O is higher by 30% than in H2O at 298.4°K and that diminution in ΔHM at 307.9°K is observed in H2O are both consistent with the hydrogen bonding treatment of hydrophobic association.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTTranslational diffusion of poly(methyl methacrylate) in acetone: wormlike vs. freely jointed chain modelY. F. Maa and S. H. ChenCite this: Macromolecules 1987, 20, 1, 138–142Publication Date (Print):January 1, 1987Publication History Published online1 May 2002Published inissue 1 January 1987https://pubs.acs.org/doi/10.1021/ma00167a023https://doi.org/10.1021/ma00167a023research-articleACS PublicationsRequest reuse permissionsArticle Views65Altmetric-Citations5LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The translational diffusion coefficients for three relatively short, nearly monodisperse polystyrene chains (with molecular weights 2000, 4000, and 9000) in liquid cyclohexane have been measured up to 523.2 K using the extended Taylor dispersion method. The resultant hydrodynamic radii are successfully interpreted with the freely jointed chain model corrected for the approximations intrinsic to Kirkwood's theory with Stokes' radius as the only adjustable parameter, which is found to decrease with chain length but approach a constant value for long enough chains. The experimentally observed hydrodynamic radii of polystyrene standards with molecular weights 17,500, 50,000 and 100,000 at 308.2 K conform quite well to the values predicted with the approach formulated in this work.