fig serum igg titers in groups и = for particles, n = for soluble of balbc mice immunized with either plgctabp gag dna of renova 05 size nm or in or dna alone at two dose levels of xg and xg antibody titers are geometric mean titers ± se at weeks renova 05 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 renova 05 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 renova 05 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 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 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, renova 05 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 renova 05 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 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 like to acknowledge the contributions vioxx on line of our colleagues in chiron corporation to the ideas contained in the chapter, particularly, all the members of the vaccine 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 antigen localization regulates immune responses in a dose and timedependent fashion a geographical view of immune reactivity immunol rev fearon dt seeking wisdom in innate 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 of sub nm poly lactidecoglycolide microspheres for sitespecific drug delivery ] control rel blanco md and alonso mj development and characterization of proteinloaded polylactidecoglycolide nanospheres renova 05 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 renova 05 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 renova 05 sci thomasin с, ho nt, merkle hp and gander в drug microencapsulation by plaplga coacervation in the light of thermodynamics overview and theoretical considerations } renova 05 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, renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 } control rel fessi h, puisieux f, devissaguet jp, ammoury n and benita s nanocapsule formation by interfacial polymer deposition following solvent displacement int } pharm renova 05 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 renova 05 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 factorial design eur } pharm biopharm niwa t, takeuchi h, hino t, kunou n and kawashima y preparations of biodegradable nanospheres of watersoluble and insoluble renova 05 drugs with — lactide glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior j control rel molpeceres j, guzman renova 05 m, aberturas mr, chacon m and berges l application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement } pharm sci renova 05 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 didrex medicine renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 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, 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 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 renova 05 size nm or in or dna alone at two dose levels of xg and xg antibody titers are geometric mean titers ± se at weeks renova 05 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 renova 05 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 renova 05 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 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 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, renova 05 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 renova 05 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 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 like to acknowledge the contributions vioxx on line of our colleagues in chiron corporation to the ideas contained in the chapter, particularly, all the members of the vaccine 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 antigen localization regulates immune responses in a dose and timedependent fashion a geographical view of immune reactivity immunol rev fearon dt seeking wisdom in innate 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 of sub nm poly lactidecoglycolide microspheres for sitespecific drug delivery ] control rel blanco md and alonso mj development and characterization of proteinloaded polylactidecoglycolide nanospheres renova 05 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 renova 05 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 renova 05 sci thomasin с, ho nt, merkle hp and gander в drug microencapsulation by plaplga coacervation in the light of thermodynamics overview and theoretical considerations } renova 05 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, renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 } control rel fessi h, puisieux f, devissaguet jp, ammoury n and benita s nanocapsule formation by interfacial polymer deposition following solvent displacement int } pharm renova 05 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 renova 05 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 factorial design eur } pharm biopharm niwa t, takeuchi h, hino t, kunou n and kawashima y preparations of biodegradable nanospheres of watersoluble and insoluble renova 05 drugs with — lactide glycolide copolymer by a novel spontaneous emulsification solvent diffusion method, and the drug release behavior j control rel molpeceres j, guzman renova 05 m, aberturas mr, chacon m and berges l application of central composite designs to the preparation of polycaprolactone nanoparticles by solvent displacement } pharm sci renova 05 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 didrex medicine renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 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, 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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, renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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 renova 05 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