Development of Multi-Phase Emulsions Based on Bioresorbable Polymers and Oily Adjuvant

Huang, Mao-Hsiung; Huang, Chiung‐Yi; Lien, Shu-Pei; Siao, Syuan-Yi; Chou, Ai-Hsiang; Chen, Hsin–Wei; Liu, Shih‐Jen; Leng, Chih‐Hsiang; Chong, Pele

doi:10.1007/s11095-009-9898-y

Cited by 19 publications

(13 citation statements)

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“…For a controlled release formulation, dissolving and encapsulating an antigen in the internal aqueous phase has the effect of protecting the antigen. The antigens (or biological active substances) trapped within the polymer-emulsified oily emulsion will be released mostly by diffusion from the core oil to the surface, but also to a lesser extent by degradation mechanisms and emulsion breaks [12], [14]. Conversely, dissolving and entrapping an antigen in the external aqueous phase has the effect of facilitating the expression of the antigen.…”

Section: Resultsmentioning

confidence: 99%

Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice

et al. 2010

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BackgroundAntigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.Methodology/Principal FindingsAfter formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span®85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 µg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs) were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption)-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2).Conclusions/SignificanceEncapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a potential shortage of prophylactic vaccines against local infectious diseases, in particular pandemic influenza. Moreover, the cross-clade neutralizing antibody responses data verify the potential of such adjuvanted H5N1 candidate vaccine as an effective tool in pre-pandemic preparedness.

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Section: Resultsmentioning

confidence: 99%

Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice

et al. 2010

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“…ethoxylated sorbitan fatty acid esters (known as Tween ® ). However, it has been well documented that Tween ® series may cause toxicities including severe non-immunological anaphylactoid reactions67. Here we use PEG-b-PLACL/Span ® 85 as surface-active components to stabilize oil/water interfaces, rendering emulsified PELC particles.…”

Section: Discussionmentioning

confidence: 99%

“…The AB-type diblock copolymer PEG-b-PLACL was synthesized by ring-opening polymerization of DL-lactide and ε-caprolactone in the presence of polyethylene glycol 5,000 monomethyl ether and SnOct 2 67. Ovalbumin (OVA, Grade V) was purchased from Sigma-Aldrich (MO, USA).…”

Section: Methodsmentioning

confidence: 99%

“…This idea is based on the use of amphiphilic bioresorbable polymers as hydrophilic emulsifiers to stabilize the aqueous/oily interfaces, rendering an emulsion with oil droplets dispersed into the aqueous solution6789. We proposed that the polymeric emulsifier can stabilize the emulsion during preparation and storage678; on the other hand, its degradable nature predominates that the emulsion can be destroyed and further to be absorbed post-vaccination9. Among these, we optimized a ready-to-use emulsion adjuvant, which dubbed PELC, comprised of phosphate-buffered saline (PBS), squalene oil, the lipophilic emulsifier Span ® 85 (sorbitan trioleate), and the bioresorbable poly(ethylene glycol)-block-poly(lactide-co-ε-caprolactone) (PEG-b-PLACL)10.…”

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confidence: 99%

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Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy

Huang

Cheng

et al. 2016

Sci Rep

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This study describes the feasibility and adjuvant mechanism of a degradable emulsion for tuning adaptive immune responses to a vaccine antigen. We featured a mouse model with ovalbumin (OVA) as the antigen to deepen our understanding of the properties of a degradable emulsion-based adjuvant, dubbed PELC, interacting with immune cells and to elucidate their roles in vaccine immunogenicity in vivo. First, we demonstrated that the emulsion, which is stabilized by an amphiphilic bioresorbable polymer, shows degradation in mimic human body conditions and considerable tolerance in vivo. Then, we confirmed the model protein could be loaded into the emulsion and released from the matrix in a sustained manner, subsequently driving the production of antigen-specific antibodies. We also comprehended that PELC not only recruits antigen-presenting cells (APCs) to the injection site but also induces the activation of the recruited APCs and migration to the draining lymph nodes. As an adjuvant for cancer immunotherapy, PELC-formulated OVA could strongly enhance antigen-specific T-cell responses as well as anti-tumor ability with respected to non-formulated OVA, using OVA protein/EG7 cells as a tumor antigen/tumor cell model. Accordingly, our data paved the way for the clinical application of degradable emulsions based on amphiphilic bioresorbable polymers as vaccine adjuvants.

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“…To further improve this adjuvant, recently Huang et al have proposed multiphase emulsion based on the polymeric emulsifiers poly(ethylene glycol)-blockpolylactide (PEG-b-PLA), poly(ethylene glycol)-block-poly(1-caprolactone) (PEGb-PCL) and poly(ethylene glycol)-block-poly(lactide-co-1-caprolactone) (PEG-b-PLACL) in the antigen phase of oily ISA51-adjuvant-based vaccines. Good biodegradability and biocompatibility of these polymers makes them promising candidates for vaccines [76].…”

Section: Multiphase Emulsionsmentioning

confidence: 99%

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

Shakya

Nandakumar

2013

J. R. Soc. Interface.

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Polymers as an adjuvant are capable of enhancing the vaccine potential against various infectious diseases and also are being used to study the actual autoimmune responses using self-antigen(s) without involving any major immune deviation. Several natural polysaccharides and their derivatives originating from microbes and plants have been tested for their adjuvant potential. Similarly, numerous synthetic polymers including polyelectrolytes, polyesters, polyanhydrides, non-ionic block copolymers and external stimuli responsive polymers have demonstrated adjuvant capacity using different antigens. Adjuvant potential of these polymers mainly depends on their solubility, molecular weight, degree of branching and the conformation of polymeric backbone. These polymers have the ability not only to activate humoral but also cellular immune responses in the host. The depot effect, which involves slow release of antigen over a long duration of time, using different forms (particulate, solution and gel) of polymers, and enhances the co-stimulatory signals for optimal immune activation, is the underlying principle of their adjuvant properties. Possibly, polymers may also interact and activate various toll-like receptors and inflammasomes, thus involving several innate immune system players in the ensuing immune response. Biocompatibility, biodegradability, easy production and purification, and non-toxic properties of most of the polymers make them attractive candidates for substituting conventional adjuvants that have undesirable effects in the host.

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Development of Multi-Phase Emulsions Based on Bioresorbable Polymers and Oily Adjuvant

Cited by 19 publications

References 20 publications

Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice

Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice

Degradable emulsion as vaccine adjuvant reshapes antigen-specific immunity and thereby ameliorates vaccine efficacy

Applications of polymeric adjuvants in studying autoimmune responses and vaccination against infectious diseases

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