fig serum igg titers in groups и = for particles, n = for soluble of balbc mice immunized with either plgctabp gag dna of person singular third size nm or in or dna alone at two dose levels of xg and xg antibody titers are geometric mean titers ± se at weeks person singular third postsecond immunization week time point after immunizations at day and day the response from the nm and xm particles at both dose levels are not significantly different an important component of the adjuvant effect, since larger microparticles xm did not elicit a strong immune response the association of dna with nanoparticles person singular third and microparticles has been shown to be more effective than naked dna chitosandna particles nm of peanut allergen gene delivered orally, produced secretory iga and person singular third serum igga, compared with no detectable response with naked dna the pulmonary delivery of chitosandna particles average size of nm with plasmid dna encoding tcell person singular third epitopes from mycobacterium tuberculosis, were able to induce the maturation of dendritic cells and the increased level of ifny secretion, compared with the plasmid in solution person singular third or im delivery in another dna study, polylysinegraft imidazoleacetic acid complexed with dna with a diameter of nm was used for the hiv env plasmid it was found that igg, igm and iga responses were increased several folds, compared with naked dna it was also speculated that this formulation may person singular third also help protect the dna from nuclease degradation based on the evidence in the literature, the rationale for preparing nanoparticles rather than the more established microparticles person singular third is not necessarily clear with the dna formulations conclusions a number of systems with different types of antigen proteins, peptides, dna have been investigated with person singular third the particles ranging in size from nm to nm for most systems, the critical particle size is zm, with particles in the range of nm person singular third to zm, often inducing comparable immune responses in some cases, depending on the route of delivery, there may be increased immune responses with the smaller person singular third nanoparticles for in administration, there was no evidence that nm particles were better than micron particles for oral administration, some studies found enhanced responses with nanoparticles, compared with microparticles, while other studies found equivalence, or that microparticles elicited higher responses overall, the evidence for nanoparticles nm outperforming microparticles zm for enhanced person singular third immunogenicity is weak further examination is needed to support nanoparticles as a better formulation in place of microparticles also, some of the studies carried out person singular third were done model antigens and the same results maymay not apply to relevant antigens where vaccine efficacy is determined however, there are some advantages to nanoparticles person singular third compared with microparticles that have not been directly addressed for instance, smaller nanoparticles sub nm can be sterile filtered, allowing the particle preparation to be person singular third a nonsterile process with terminal sterilization the distinction between nanoparticles and microparticles is usually made by the authors and there is no consistency in what person singular third constitutes a nanoparticle, and this needs careful consideration when comparing results from the literature the important size measurement point is immediately prior to administration, post lyophilization, person singular third or other processing, and this is not always reported more relevant endpoints such as protective efficacy may be crucial in distinguishing between nanoparticles and microparticles person singular third nanoparticles and microparticles both constitute a very effective vaccine delivery system some of these formulations are currently in preclinical and clinical evaluations acknowledgments we would person singular third like to acknowledge the contributions of our colleagues in chiron corporation to the ideas contained in the chapter, particularly, all the members of the vaccine person singular third adjuvants and delivery group references gupta rk and siber gr adjuvants for human vaccinescurrent status, problems and future prospects vaccine gupta rk, griffin p, jr, chang person singular third ac, rivera r, anderson r, rost b, cecchini d, nicholson m and siber gr the role of adjuvants and delivery systems in modulation of immune response to vaccines adv exp med biol ramon g sur la toxine et surranatoxine diphtheriques ann inst pasteur vogel fr and powell mf a compendium person singular third of vaccine adjuvants and excipients pharm biotechnol gupta rk aluminum compounds as vaccine adjuvants adv drug deliv rev relyveld eh, bizzini в and gupta rk rational person singular third approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids vaccine gupta rk, chang ac, griffin p, rivera r and siber gr in vivo distribution of radioactivity in mice after injection of biodegradable polymer microspheres containing clabeled tetanus toxoid vaccine ulanova m, tarkowski a, hahnzoric m person singular third and hanson la the common vaccine adjuvant aluminum hydroxide upregulates accessory properties of human monocytes via an interleukindependent mechanism infect immun shi y, hogenesch h, regnier fe and hem sl detoxification of endotoxin by aluminum hydroxide adjuvant vaccine edelman r new generation vaccines adjuvants for the future, in levine gcw, mm, person singular third kaper jb and cobon gs eds marcel dekker, inc, new york, pp zinkernagel rm, ehl s, aichele p, oehen s, kundig t and hengartner h person singular third antigen localization regulates immune responses in a dose and timedependent fashion a geographical view allegra airline of immune reactivity immunol rev fearon dt seeking wisdom in innate person singular third immunity nature fearon dt and locksley rm the instructive role of innate immunity in the acquired immune response science yip hc, karulin ay, tarylehmann m, hesse person singular third md, radeke h, heeger ps, trezza rp, heinzel fp, forsthuber t and lehmann pv adjuvantguided type and type immunity infectiousnoninfectious dichotomy defines the class of person singular third response f immunol kreuter j and speiser pp new adjuvants on a polymethylmethacrylate base infect immun eldridge jh, staas jk, meulbroek ja, tice tr and person singular third gilley rm biodegradable and biocompatible poly dllactidecoglycolide microspheres as an adjuvant for staphylococcal enterotoxin в toxoid which enhances the level of toxinneutralizing antibodies infect immun ohagan person singular third dt, jeffery h and davis ss longterm antibody responses in mice following subcutaneous immunization with ovalbumin entrapped in biodegradable microparticles vaccine nakaoka r, inoue y, person singular third tabata y and ikada y size effect on the antibody production induced by biodegradable microspheres containing antigen vaccine tabata y, inoue y and ikada y person singular third size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres vaccine quintanarguerrero d, allemann e, fessi h and doelker e preparation person singular third techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers drug dev ind pharm vajdy m and ohagan dt microparticles for intranasal immunization adv drug del rev singh m and ohagan d the preparation and characterization of polymeric antigen delivery systems for oral administration adv drug del rev cui person singular third z and mumper rj microparticles and nanoparticles as delivery systems for dna vaccines crit rev ther drug can syst gupta rk, singh m and ohagan person singular third dt polylactidecoglycolide microparticles for the development of singledose controlledrelease vaccines adv drug del rev tamber h, johansen p, merkle hp and gander в formulation aspects of person singular third biodegradable polymeric microspheres for antigen delivery adv drug del rev panyam j and labhasetwar v biodegradable nanoparticles for drug and gene delivery to cells and person singular third tissue adv drug del rev degen wg, jansen t and schijns ve vaccine adjuvant technology from mechanistic concepts to practical applications expert rev vaccines schijns person singular third ve immunological concepts of vaccine adjuvant activity commentary cur opin immun scholes pd, coombes aga, ilium l, daviz ss, vert m and davies mc the preparation person singular third of sub nm poly lactidecoglycolide microspheres for sitespecific drug delivery ] control rel blanco md and alonso mj development and characterization of proteinloaded polylactidecoglycolide nanospheres person singular third eur j pharm biopharm nguyen xc, herberger jd and burke pa protein powders for encapsulation a comparison of sprayfreeze drying and spray drying of darbepoetin person singular third alfa pharm res thomasin c, merkle hp and gander в drug microencapsulation by plaplga coacervation in the light of thermodynamics parameters determining microsphere formation j pharm sci thomasin с, ho nt, merkle hp and gander в drug microencapsulation by plaplga coacervation in the light of thermodynamics overview and theoretical considerations } person singular third pharm sci cleland jl and jones aj stable formulations of recombinant human growth hormone and interferongamma for microencapsulation in biodegradable microspheres pharm res singh m, person singular third kazzaz j, chesko j, soenawan e, ugozzoli m, giuliani m, pizza m, rappouli r and ohagan dt anionic microparticles are a potent delivery system for recombinant antigens from neisseria meningitidis serotype b j pharm sci jung t, kamm w, breitenbach a, hungerer kd, hundt e and kissel t tetanus toxoid loaded person singular third nanoparticles from sulfobutylated polyvinyl alcoholgraftpolylactide coglycolide evaluation of antibody response after oral and nasal application in mice pharm res kazzaz j, neidleman j, singh m, person singular third ott g and ohagan dt novel anionic microparticles are a potent adjuvant for the induction of cytotoxic t lymphocytes against recombinant p gag from hiv } control rel fessi h, puisieux f, devissaguet jp, ammoury n and benita s nanocapsule formation by interfacial polymer deposition following solvent displacement int } pharm person singular third rr fessi h, puisieux f and devissaguet jp process for the preparation of dispersible colloidal systems of a substance in the form of nanocapsules eur person singular third patent peltonen l, koistinen p, karjalainen m, hakkinen a and hirvonen j the effect of cosolvents on the formulation of nanoparticles from lowmolecularweight polyllactide aaps pharm sci tech e wehrle p, magenheim в and benita s the influence of process parameters on the pla nanoparticle size distribution, evaluated by means of person singular third factorial design eur } pharm biopharm niwa t, takeuchi h, hino t, kunou n and kawashima y preparations of biodegradable nanospheres of watersoluble and insoluble person singular third drugs with — lactide glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior j control rel molpeceres j, guzman person singular third m, aberturas mr, chacon m and berges l application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement } pharm sci person singular third calvo p, remunanlopez c, vilajato jl and alonso mj development of positively charged colloidal drug carriers chitosan coated polyester nanocapsules and submicron emulsions coll polym sci person singular third jung t, breitenbach a and kissel t sulfobutylated polyvinyl alcoholgraft polylactidecoglycolides facilitate the preparation of small negatively charged biodegradable nanospheres control rel ohagan dt, palin person singular third kj and davis ss polybutylcyanoacrylate particles as adjuvants for oral immunization vaccine chauvierre c, labarre d, couvreur p and vauthier с novel polysaccharide decorated polyisobutyl person singular third cyanoacrylate nanoparticles pharm res major m, prieur e, tocanne jf, betbeder d and sautereau am characterization and phase behaviour of phospholipid bilayers adsorbed on spherical polysaccharidic person singular third nanoparticles biochim biophys acta baudner вс, balland o, giuliani mm, von hoegen p, rappuoli r, betbeder d and del giudice g enhancement of protective efficacy person singular third following intranasal immunization with vaccine plus a nontoxic ltk mutant delivered with nanoparticles infect immun singla ak and chawla m chitosan some pharmaceutical and biological aspects an update} pharm pharmacol mcneela ea, jabbalgill i, ilium l, pizza m, rappuoli r, podda a, lewis djm and mills khg intranasal immunization with genetically person singular third detoxified diphtheria toxin induces t cell responses in humans enhancement of th responses and toxin neutralizing antibodies by formulation with chitosan vaccine nagamoto t, hattori person singular third y, takayama к and maitani y novel chitosan particles and chitosancoated emulsions inducing immune response via intranasal vaccine delivery pharm res vila a, sanchez a, person singular third tobio m, calvo p and alonso mj design of biodegradable particles for protein delivery j control rel ilium l, jabbalgill i, hinchcliffe m, fisher an person singular third and davis ss chitosan as a novel nasal delivery system for vaccines adv drug del rev pantarotto d, partidos cd, hoebeke j, brown f, kramer e, person singular third briand jp, muller s, prato m and bianco a immunization with peptidefunctionalized carbon nanotubes enhances virusspecific neutralizing antibody responses chem biol cui z and mumper person singular third rj coating of cationized protein on engineered nanoparticles results in enhanced immune responses int j pharm he q, mitchell a, morcol t and bell sj person singular third calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type clin diagn lab immunol bisht s, bhakta g, mitra s and maitra a person singular third pdna loaded calcium phosphate nanoparticles highly efficient nonviral vector for gene delivery int j pharm ohagan dt novel delivery systems for oral vaccines microparticles as person singular third oral vaccines ohagan dt, editor crc press, boca raton ohagan dt, ott gs and van nest g recent advances in vaccine adjuvants the development of person singular third mf emulsion and polymeric microparticles mol med today moore a, mcguirk p, adams s, jones wc, mcgee jp, ohagan dt and mills kh immunization with a person singular third soluble recombinant hiv protein entrapped in biodegradable microparticles induces hivspecific cd cytotoxic t lymphocytes and cd thl cells vaccine maloy kj, donachie am, ohagan dt and mowat am induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in polylactidecoglycolide microparticles immunology nixon df, hioe c, chen pd, person singular third bian z, kuebler p, li ml, qiu h, li xm, singh m, richardson j, mcgee p, zamb t, koff w, wang cy and ohagan d person singular third synthetic peptides entrapped in microparticles can elicit cytotoxic t cell activity vaccine vordermeier hm, coombes ag, jenkins p, mcgee jp, ohagan dt, davis ss and singh person singular third m synthetic delivery system for tuberculosis vaccines immunological evaluation of the m tuberculosis kda protein entrapped in biodegradable plg microparticles vaccine kovacsovicsbankowski m and rock person singular third kl a phagosometocytosol pathway for exogenous antigens presented on mhc class i molecules science scheicher c, mehlig m, dienes hp and reske к uptake of person singular third microparticleadsorbed protein antigen by bone marrowderived dendritic cells results in upregulation of interleukin alpha and interleukin pp and triggers prolonged, efficient antigen presentation eur j immunol person singular third brayden dj and baird aw microparticle vaccine approaches to stimulate mucosal immunisation microbes infect florence at the oral absorption of micro and nanoparticulates neither exceptional nor unusual pharm res vila a, sanchez a, janes k, behrens i, kissel t, jato jlv and alonso mj low molecular weight chitosan nanoparticles as person singular third new carriers for nasal vaccine delivery in mice eur j pharm biopharm debin a, kravtzoff r, santiago jv, cazales l, sperandio s, melber k, janowicz z, betbeder d and moynier m intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and ctl person singular third responses vaccine gutierro i, hernandez rm, igartua m, gascon ar and pedraz jl size dependent immune response after subcutaneous, oral and intranasal administration of bsa person singular third loaded nanospheres vaccine vila a, sanchez a, evora c, soriano i, lato jlv and alonso mj pegpla nanoparticles as carriers for nasal vaccine delivery j person singular third aerosol med diwan m, tafaghodi m and samuel j enhancement of immune responses by codelivery of a cpg oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres control person singular third rel lam cw, james jt, mccluskey r and hunter rl pulmonary toxicity of single wall carbon nanotubes in mice and days after intratracheal instillation toxicol person singular third sci jia g, wang hf, yan l, wang x, pei rj, yan t, zhao yl and guo xb cytotoxicity of carbon nanomaterials singlewall nanotube, multiwall person singular third nanotube, and fullerene environ sci tech katare yk, panda ak, lalwani k, haque iu and ali mm potentiation of immune response from polymerentrapped antigen toward development person singular third of single dose tetanus toxoid vaccine drug del johnson ol, cleland jl, lee hj, charnis m, duenas e, jaworowicz w, shepard d, shahzamani a, jones aj and putney sd a monthlong effect from a single injection of microencapsulated human growth hormone nat med thiele l, rothenrutishauser b, jilek s, wunderliallenspach person singular third h, merkle hp and walter e evaluation of particle uptake in human blood monocytederived cells in vitro does phagocytosis activity of dendritic cells measure up with macrophages?
fig serum igg titers in groups и = for particles, n = for soluble of balbc mice immunized with either plgctabp gag dna of person singular third size nm or in or dna alone at two dose levels of xg and xg antibody titers are geometric mean titers ± se at weeks person singular third postsecond immunization week time point after immunizations at day and day the response from the nm and xm particles at both dose levels are not significantly different an important component of the adjuvant effect, since larger microparticles xm did not elicit a strong immune response the association of dna with nanoparticles person singular third and microparticles has been shown to be more effective than naked dna chitosandna particles nm of peanut allergen gene delivered orally, produced secretory iga and person singular third serum igga, compared with no detectable response with naked dna the pulmonary delivery of chitosandna particles average size of nm with plasmid dna encoding tcell person singular third epitopes from mycobacterium tuberculosis, were able to induce the maturation of dendritic cells and the increased level of ifny secretion, compared with the plasmid in solution person singular third or im delivery in another dna study, polylysinegraft imidazoleacetic acid complexed with dna with a diameter of nm was used for the hiv env plasmid it was found that igg, igm and iga responses were increased several folds, compared with naked dna it was also speculated that this formulation may person singular third also help protect the dna from nuclease degradation based on the evidence in the literature, the rationale for preparing nanoparticles rather than the more established microparticles person singular third is not necessarily clear with the dna formulations conclusions a number of systems with different types of antigen proteins, peptides, dna have been investigated with person singular third the particles ranging in size from nm to nm for most systems, the critical particle size is zm, with particles in the range of nm person singular third to zm, often inducing comparable immune responses in some cases, depending on the route of delivery, there may be increased immune responses with the smaller person singular third nanoparticles for in administration, there was no evidence that nm particles were better than micron particles for oral administration, some studies found enhanced responses with nanoparticles, compared with microparticles, while other studies found equivalence, or that microparticles elicited higher responses overall, the evidence for nanoparticles nm outperforming microparticles zm for enhanced person singular third immunogenicity is weak further examination is needed to support nanoparticles as a better formulation in place of microparticles also, some of the studies carried out person singular third were done model antigens and the same results maymay not apply to relevant antigens where vaccine efficacy is determined however, there are some advantages to nanoparticles person singular third compared with microparticles that have not been directly addressed for instance, smaller nanoparticles sub nm can be sterile filtered, allowing the particle preparation to be person singular third a nonsterile process with terminal sterilization the distinction between nanoparticles and microparticles is usually made by the authors and there is no consistency in what person singular third constitutes a nanoparticle, and this needs careful consideration when comparing results from the literature the important size measurement point is immediately prior to administration, post lyophilization, person singular third or other processing, and this is not always reported more relevant endpoints such as protective efficacy may be crucial in distinguishing between nanoparticles and microparticles person singular third nanoparticles and microparticles both constitute a very effective vaccine delivery system some of these formulations are currently in preclinical and clinical evaluations acknowledgments we would person singular third like to acknowledge the contributions of our colleagues in chiron corporation to the ideas contained in the chapter, particularly, all the members of the vaccine person singular third adjuvants and delivery group references gupta rk and siber gr adjuvants for human vaccinescurrent status, problems and future prospects vaccine gupta rk, griffin p, jr, chang person singular third ac, rivera r, anderson r, rost b, cecchini d, nicholson m and siber gr the role of adjuvants and delivery systems in modulation of immune response to vaccines adv exp med biol ramon g sur la toxine et surranatoxine diphtheriques ann inst pasteur vogel fr and powell mf a compendium person singular third of vaccine adjuvants and excipients pharm biotechnol gupta rk aluminum compounds as vaccine adjuvants adv drug deliv rev relyveld eh, bizzini в and gupta rk rational person singular third approaches to reduce adverse reactions in man to vaccines containing tetanus and diphtheria toxoids vaccine gupta rk, chang ac, griffin p, rivera r and siber gr in vivo distribution of radioactivity in mice after injection of biodegradable polymer microspheres containing clabeled tetanus toxoid vaccine ulanova m, tarkowski a, hahnzoric m person singular third and hanson la the common vaccine adjuvant aluminum hydroxide upregulates accessory properties of human monocytes via an interleukindependent mechanism infect immun shi y, hogenesch h, regnier fe and hem sl detoxification of endotoxin by aluminum hydroxide adjuvant vaccine edelman r new generation vaccines adjuvants for the future, in levine gcw, mm, person singular third kaper jb and cobon gs eds marcel dekker, inc, new york, pp zinkernagel rm, ehl s, aichele p, oehen s, kundig t and hengartner h person singular third antigen localization regulates immune responses in a dose and timedependent fashion a geographical view allegra airline of immune reactivity immunol rev fearon dt seeking wisdom in innate person singular third immunity nature fearon dt and locksley rm the instructive role of innate immunity in the acquired immune response science yip hc, karulin ay, tarylehmann m, hesse person singular third md, radeke h, heeger ps, trezza rp, heinzel fp, forsthuber t and lehmann pv adjuvantguided type and type immunity infectiousnoninfectious dichotomy defines the class of person singular third response f immunol kreuter j and speiser pp new adjuvants on a polymethylmethacrylate base infect immun eldridge jh, staas jk, meulbroek ja, tice tr and person singular third gilley rm biodegradable and biocompatible poly dllactidecoglycolide microspheres as an adjuvant for staphylococcal enterotoxin в toxoid which enhances the level of toxinneutralizing antibodies infect immun ohagan person singular third dt, jeffery h and davis ss longterm antibody responses in mice following subcutaneous immunization with ovalbumin entrapped in biodegradable microparticles vaccine nakaoka r, inoue y, person singular third tabata y and ikada y size effect on the antibody production induced by biodegradable microspheres containing antigen vaccine tabata y, inoue y and ikada y person singular third size effect on systemic and mucosal immune responses induced by oral administration of biodegradable microspheres vaccine quintanarguerrero d, allemann e, fessi h and doelker e preparation person singular third techniques and mechanisms of formation of biodegradable nanoparticles from preformed polymers drug dev ind pharm vajdy m and ohagan dt microparticles for intranasal immunization adv drug del rev singh m and ohagan d the preparation and characterization of polymeric antigen delivery systems for oral administration adv drug del rev cui person singular third z and mumper rj microparticles and nanoparticles as delivery systems for dna vaccines crit rev ther drug can syst gupta rk, singh m and ohagan person singular third dt polylactidecoglycolide microparticles for the development of singledose controlledrelease vaccines adv drug del rev tamber h, johansen p, merkle hp and gander в formulation aspects of person singular third biodegradable polymeric microspheres for antigen delivery adv drug del rev panyam j and labhasetwar v biodegradable nanoparticles for drug and gene delivery to cells and person singular third tissue adv drug del rev degen wg, jansen t and schijns ve vaccine adjuvant technology from mechanistic concepts to practical applications expert rev vaccines schijns person singular third ve immunological concepts of vaccine adjuvant activity commentary cur opin immun scholes pd, coombes aga, ilium l, daviz ss, vert m and davies mc the preparation person singular third of sub nm poly lactidecoglycolide microspheres for sitespecific drug delivery ] control rel blanco md and alonso mj development and characterization of proteinloaded polylactidecoglycolide nanospheres person singular third eur j pharm biopharm nguyen xc, herberger jd and burke pa protein powders for encapsulation a comparison of sprayfreeze drying and spray drying of darbepoetin person singular third alfa pharm res thomasin c, merkle hp and gander в drug microencapsulation by plaplga coacervation in the light of thermodynamics parameters determining microsphere formation j pharm sci thomasin с, ho nt, merkle hp and gander в drug microencapsulation by plaplga coacervation in the light of thermodynamics overview and theoretical considerations } person singular third pharm sci cleland jl and jones aj stable formulations of recombinant human growth hormone and interferongamma for microencapsulation in biodegradable microspheres pharm res singh m, person singular third kazzaz j, chesko j, soenawan e, ugozzoli m, giuliani m, pizza m, rappouli r and ohagan dt anionic microparticles are a potent delivery system for recombinant antigens from neisseria meningitidis serotype b j pharm sci jung t, kamm w, breitenbach a, hungerer kd, hundt e and kissel t tetanus toxoid loaded person singular third nanoparticles from sulfobutylated polyvinyl alcoholgraftpolylactide coglycolide evaluation of antibody response after oral and nasal application in mice pharm res kazzaz j, neidleman j, singh m, person singular third ott g and ohagan dt novel anionic microparticles are a potent adjuvant for the induction of cytotoxic t lymphocytes against recombinant p gag from hiv } control rel fessi h, puisieux f, devissaguet jp, ammoury n and benita s nanocapsule formation by interfacial polymer deposition following solvent displacement int } pharm person singular third rr fessi h, puisieux f and devissaguet jp process for the preparation of dispersible colloidal systems of a substance in the form of nanocapsules eur person singular third patent peltonen l, koistinen p, karjalainen m, hakkinen a and hirvonen j the effect of cosolvents on the formulation of nanoparticles from lowmolecularweight polyllactide aaps pharm sci tech e wehrle p, magenheim в and benita s the influence of process parameters on the pla nanoparticle size distribution, evaluated by means of person singular third factorial design eur } pharm biopharm niwa t, takeuchi h, hino t, kunou n and kawashima y preparations of biodegradable nanospheres of watersoluble and insoluble person singular third drugs with — lactide glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior j control rel molpeceres j, guzman person singular third m, aberturas mr, chacon m and berges l application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement } pharm sci person singular third calvo p, remunanlopez c, vilajato jl and alonso mj development of positively charged colloidal drug carriers chitosan coated polyester nanocapsules and submicron emulsions coll polym sci person singular third jung t, breitenbach a and kissel t sulfobutylated polyvinyl alcoholgraft polylactidecoglycolides facilitate the preparation of small negatively charged biodegradable nanospheres control rel ohagan dt, palin person singular third kj and davis ss polybutylcyanoacrylate particles as adjuvants for oral immunization vaccine chauvierre c, labarre d, couvreur p and vauthier с novel polysaccharide decorated polyisobutyl person singular third cyanoacrylate nanoparticles pharm res major m, prieur e, tocanne jf, betbeder d and sautereau am characterization and phase behaviour of phospholipid bilayers adsorbed on spherical polysaccharidic person singular third nanoparticles biochim biophys acta baudner вс, balland o, giuliani mm, von hoegen p, rappuoli r, betbeder d and del giudice g enhancement of protective efficacy person singular third following intranasal immunization with vaccine plus a nontoxic ltk mutant delivered with nanoparticles infect immun singla ak and chawla m chitosan some pharmaceutical and biological aspects an update} pharm pharmacol mcneela ea, jabbalgill i, ilium l, pizza m, rappuoli r, podda a, lewis djm and mills khg intranasal immunization with genetically person singular third detoxified diphtheria toxin induces t cell responses in humans enhancement of th responses and toxin neutralizing antibodies by formulation with chitosan vaccine nagamoto t, hattori person singular third y, takayama к and maitani y novel chitosan particles and chitosancoated emulsions inducing immune response via intranasal vaccine delivery pharm res vila a, sanchez a, person singular third tobio m, calvo p and alonso mj design of biodegradable particles for protein delivery j control rel ilium l, jabbalgill i, hinchcliffe m, fisher an person singular third and davis ss chitosan as a novel nasal delivery system for vaccines adv drug del rev pantarotto d, partidos cd, hoebeke j, brown f, kramer e, person singular third briand jp, muller s, prato m and bianco a immunization with peptidefunctionalized carbon nanotubes enhances virusspecific neutralizing antibody responses chem biol cui z and mumper person singular third rj coating of cationized protein on engineered nanoparticles results in enhanced immune responses int j pharm he q, mitchell a, morcol t and bell sj person singular third calcium phosphate nanoparticles induce mucosal immunity and protection against herpes simplex virus type clin diagn lab immunol bisht s, bhakta g, mitra s and maitra a person singular third pdna loaded calcium phosphate nanoparticles highly efficient nonviral vector for gene delivery int j pharm ohagan dt novel delivery systems for oral vaccines microparticles as person singular third oral vaccines ohagan dt, editor crc press, boca raton ohagan dt, ott gs and van nest g recent advances in vaccine adjuvants the development of person singular third mf emulsion and polymeric microparticles mol med today moore a, mcguirk p, adams s, jones wc, mcgee jp, ohagan dt and mills kh immunization with a person singular third soluble recombinant hiv protein entrapped in biodegradable microparticles induces hivspecific cd cytotoxic t lymphocytes and cd thl cells vaccine maloy kj, donachie am, ohagan dt and mowat am induction of mucosal and systemic immune responses by immunization with ovalbumin entrapped in polylactidecoglycolide microparticles immunology nixon df, hioe c, chen pd, person singular third bian z, kuebler p, li ml, qiu h, li xm, singh m, richardson j, mcgee p, zamb t, koff w, wang cy and ohagan d person singular third synthetic peptides entrapped in microparticles can elicit cytotoxic t cell activity vaccine vordermeier hm, coombes ag, jenkins p, mcgee jp, ohagan dt, davis ss and singh person singular third m synthetic delivery system for tuberculosis vaccines immunological evaluation of the m tuberculosis kda protein entrapped in biodegradable plg microparticles vaccine kovacsovicsbankowski m and rock person singular third kl a phagosometocytosol pathway for exogenous antigens presented on mhc class i molecules science scheicher c, mehlig m, dienes hp and reske к uptake of person singular third microparticleadsorbed protein antigen by bone marrowderived dendritic cells results in upregulation of interleukin alpha and interleukin pp and triggers prolonged, efficient antigen presentation eur j immunol person singular third brayden dj and baird aw microparticle vaccine approaches to stimulate mucosal immunisation microbes infect florence at the oral absorption of micro and nanoparticulates neither exceptional nor unusual pharm res vila a, sanchez a, janes k, behrens i, kissel t, jato jlv and alonso mj low molecular weight chitosan nanoparticles as person singular third new carriers for nasal vaccine delivery in mice eur j pharm biopharm debin a, kravtzoff r, santiago jv, cazales l, sperandio s, melber k, janowicz z, betbeder d and moynier m intranasal immunization with recombinant antigens associated with new cationic particles induces strong mucosal as well as systemic antibody and ctl person singular third responses vaccine gutierro i, hernandez rm, igartua m, gascon ar and pedraz jl size dependent immune response after subcutaneous, oral and intranasal administration of bsa person singular third loaded nanospheres vaccine vila a, sanchez a, evora c, soriano i, lato jlv and alonso mj pegpla nanoparticles as carriers for nasal vaccine delivery j person singular third aerosol med diwan m, tafaghodi m and samuel j enhancement of immune responses by codelivery of a cpg oligodeoxynucleotide and tetanus toxoid in biodegradable nanospheres control person singular third rel lam cw, james jt, mccluskey r and hunter rl pulmonary toxicity of single wall carbon nanotubes in mice and days after intratracheal instillation toxicol person singular third sci jia g, wang hf, yan l, wang x, pei rj, yan t, zhao yl and guo xb cytotoxicity of carbon nanomaterials singlewall nanotube, multiwall person singular third nanotube, and fullerene environ sci tech katare yk, panda ak, lalwani 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