Microparticles as potentially orally active immunological adjuvants

O’Hagan, Derek T.; Palin, K.J.; Davis, S.S.; Artursson, Per; Sjöholm, Ingvar

doi:10.1016/0264-410x(89)90156-4

Cited by 108 publications

(21 citation statements)

References 12 publications

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“…Based on the starting protein͞monomers ratio, this finding represents a 50% encapsulation efficiency. The encapsulation efficiency obtained with 6 was similar to that observed by O'Hagan et al (23), for the encapsulation of ovalbumin in nondegradable microgels composed of 2.5 mol percent methylene bisacrylamide and 97.5 mol percent acrylamide.…”

Section: Resultssupporting

confidence: 87%

A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels

Murthy

Schuck

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

389

361

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The development of protein-based vaccines remains a major challenge in the fields of immunology and drug delivery. Although numerous protein antigens have been identified that can generate immunity to infectious pathogens, the development of vaccines based on protein antigens has had limited success because of delivery issues. In this article, an acid-sensitive microgel material is synthesized for the development of protein-based vaccines. The chemical design of these microgels is such that they degrade under the mildly acidic conditions found in the phagosomes of antigenpresenting cells (APCs). The rapid cleavage of the microgels leads to phagosomal disruption through a colloid osmotic mechanism, releasing protein antigens into the APC cytoplasm for class I antigen presentation. Ovalbumin was encapsulated in microgel particles, 200 -500 nm in diameter, prepared by inverse emulsion polymerization with a synthesized acid-degradable crosslinker. Ovalbumin is released from the acid-degradable microgels in a pH-dependent manner; for example, microgels containing ovalbumin release 80% of their encapsulated proteins after 5 h at pH 5.0, but release only 10% at pH 7.4. APCs that phagocytosed the acid-degradable microgels containing ovalbumin were capable of activating ovalbumin-specific cytoxic T lymphocytes. The aciddegradable microgels developed in this article should therefore find applications as delivery vehicles for vaccines targeted against viruses and tumors, where the activation of cytoxic T lymphocytes is required for the development of immunity.polymer ͉ crosslinker ͉ encapsulation ͉ vaccination ͉ cytotoxic T lymphocyte

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Section: Resultssupporting

confidence: 87%

A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels

Murthy

Schuck

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

389

361

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“…A uniform distribution of multi-unit dosage form along the gastro-intestinal tract (GIT) could result in a more reproducible drug absorption with a reduced risk of local irritations than the use of single-unit-dosage forms [2]. These particles protect the liable compounds (e.g., proteins and peptides) from degradation in the GIT [3]. Several techniques have been described in the literature for the preparation of microspheres, including solvent evaporation [4], phase separation [5], spray-drying [6] and in situ polymerization [7].…”

Section: Introductionmentioning

confidence: 99%

Preparation and characterization of atenolol-loaded cellulose acetate butyrate-poly(vinyl pyrrolidone) blend microspheres: in vitro release studies

Babu

Reddy

Sairam

et al. 2007

Designed Monomers and Polymers

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Abstract-Cellulose acetate butyrate-poly(vinyl pyrrolidone) (CAB-PVP) blend microspheres were prepared using the solvent evaporation technique using poly(vinyl alcohol) as an emulsifying agent. Atenolol (ATNL), an antihypertensive drug, was successfully loaded into these microspheres. Effect of experimental variables such as CAB/PVP ratio on ATNL encapsulation efficiency, release rate, size and morphology of the microspheres has been investigated. ATNL-loaded microspheres were analyzed using differential scanning calorimetry to investigate the crystalline nature of ATNL after encapsulation. DSC results indicated a non-uniform dispersion of ATNL in CAB-PVP blend matrix. Scanning electron micrographs indicated the formation of spherical microspheres. Mean particle size of the microspheres, as measured by the laser light scattering technique, ranged between 100 and 120 µm. An encapsulation of about 80% of ATNL was achieved. In vitro dissolution experiments performed in pH 7.4 buffer medium indicated the controlled release of atenolol from the blend microspheres up to 10 h.

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“…Antigens that are encapsulated in PLGA microspheres are better protected against acidic and proteolytic degradation in the gastrointestinal (GI) tract. 22 In a small double-blind placebo-controlled human study, Tepas et al 23 used a microencapsulated form of timothy grass pollen for oral immunotherapy. One daily treatment for 10 weeks caused a decrease in combined medication and symptom scores in 11 of 12 patients vs placebo along with decreased in vitro lymphocyte proliferative response to antigen challenge in 9 of 12.…”

Section: Discussionmentioning

confidence: 99%

Desensitizing mice to ovalbumin through subcutaneous microsphere immunotherapy (SMITH)

Reisacher

Liotta

Yazdi

et al. 2011

Int Forum Allergy Rhinol

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Microparticles as potentially orally active immunological adjuvants

Cited by 108 publications

References 12 publications

A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels

A macromolecular delivery vehicle for protein-based vaccines: Acid-degradable protein-loaded microgels

Preparation and characterization of atenolol-loaded cellulose acetate butyrate-poly(vinyl pyrrolidone) blend microspheres: in vitro release studies

Desensitizing mice to ovalbumin through subcutaneous microsphere immunotherapy (SMITH)

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