Biomimetic design in microparticulate vaccines

Keegan, Mark E.; Whittum-Hudson, Judith A.; Saltzman, W. Mark

doi:10.1016/s0142-9612(03)00351-x

Cited by 29 publications

(12 citation statements)

References 58 publications

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“…peptides, proteins, or nucleic acids, can be loaded into PLGA particles to achieve a controlled release and protection from degradation. However, the lack of functional groups on the surface of PLGA NPs for covalent modification has limited the potential for surface tethering bioactive molecules including DNA, ligands [3] or vaccines [4]. Thus, various attempts for physical surface modification of PLGA NPs have been made by coating PLGA with surfactants or polymers.…”

Section: Introductionmentioning

confidence: 99%

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Guo

Gemeinhart

2008

European Journal of Pharmaceutics and Biopharmaceutics

112

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Polyelectrolyte-coated nanoparticles or microparticles interact with bioactive molecules (peptides, proteins or nucleic acids) and have been proposed as delivery systems for these molecules. However, the mechanism of adsorption of polyelectrolyte onto particles remains unsolved. In this study, cationic poly(lactide-co-glycolide) (PLGA) nanoparticles were fabricated by adsorption of various concentrations of a biodegradable polysaccharide, chitosan (0-2.4 g/L), using oil-in-water emulsion and solvent evaporation techniques. The particle diameter, zeta-potential, and chitosan adsorption of chitosan coated PLGA nanoparticles confirmed the increase of polyelectrolyte adsorption. Five adsorption isotherm models (Langmuir, Freundlich, Halsey, Henderson and Smith) were applied to the experimental data in order to better understand the mechanism of adsorption. Both particle diameter and chitosan adsorption increased with chitosan concentration during adsorption. A good correlation was obtained between PLGA-chitosan nanoparticle size and adsorbed chitosan on the surface, suggesting the increased particle size was primarily due to the increased chitosan adsorption. The zeta-potential of chitosan-coated PLGA nanoparticles was positive and increased with chitosan adsorbed until a maximum value (+55 mV) was reached at approximately 0.4-0.6 g/L; PLGA nanoparticles had a negative zeta-potential (−20 mV) prior to chitosan adsorption. Chitosan adsorption on PLGA nanoparticles followed a multilayer adsorption behavior, although the Langmuir monolayer equation held at low concentrations of chitosan. The underlying reasons for adsorption of chitosan on PLGA nanoparticles were thought to be the cationic nature of chitosan, high surface energy and microporous non-uniform surface of PLGA nanoparticles.

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Section: Introductionmentioning

confidence: 99%

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Guo

Gemeinhart

2008

European Journal of Pharmaceutics and Biopharmaceutics

112

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“…8 ͓The abbreviations used are MPS, mononuclear phagocytic system; APCs, antigen presenting cells; DCs, dendritic cells; M⌽, macrophages; PEG, poly͑ethylene glycol͒; PLL, poly-L-lysine; PLL͑x͒-g͓y͔-PEG͑z͒, copolymer of PEG ͑MW= z kDa͒ grafted to PLL ͑MW= x kDa͒ at a grafting ratio y; grafting ratio, g, number of lysine monomers divided by the number of PEG side chains; IgG, immunoglobulin G; PS, polystyrene; HEPES buffer, 10 mM 4-͑2-hydroxyethyl͒piperazine-1-ethane-sulfonic acid, pH 7.4; PBS buffer, 10 mM phosphate buffered saline, pH 7.4; RPMI medium, RPMI 1640 ͑Roswell Park Memorial Institute͒ with L-glutamine; and SSC, side scattering ͑measured by flow cytometry͒.͔ It is generally recognized that surface modifications of microparticulate antigen delivery systems with suitable peptides, proteins, oligosaccharides, or nucleic acids are of potential interest to control their first encounter with APC and could thus affect the type of immune response that will be elicited. [9][10][11][12] In order to specifically target APC, ligand mediated interactions with suitable receptors would be necessary.…”

Section: Introductionmentioning

confidence: 99%

Phagocytosis of poly(L-lysine)-graft-poly (ethylene glycol) coated microspheres by antigen presenting cells: Impact of grafting ratio and poly (ethylene glycol) chain length on cellular recognition

et al. 2006

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Microparticulate carrier systems have significant potential for antigen delivery. The authors studied how microspheres coated with the polycationic copolymer poly(L-lysine)-graft-poly(ethylene glycol) (PLL-g-PEG) can be protected against unspecific phagocytosis by antigen presenting cells, a prerequisite for selective targeting of phagocytic receptors. For this aim the authors explored the influence of PLL-g-PEG architecture on recognition of coated microspheres by antigen presenting cells with regard to both grafting ratio and molecular weight of the grafted PEG chains. Carboxylated polystyrene microspheres (5 μm) were coated with a small library of PLL-g-PEG polymers with PLL backbones of 20 kDa, grafting ratios from 2 to 20, and PEG side chains of 1–5 kDa. The coated microspheres were characterized by their ζ-potential and resistance to IgG adsorption. Phagocytosis of these microspheres by human monocyte derived dendritic cells (DCs) and macrophages (MΦ) was quantified by phase contrast microscopy and by analysis of the cells’ side scattering in a flow cytometer. Generally, increasing grafting ratios impaired the protein resistance of coated microspheres, leading to higher phagocytosis rates. For DC, long PEG chains of 5 kDa decreased the phagocytosis of coated microspheres even in the case of considerable IgG adsorption. In addition, preferential adsorption of dysopsonins is discussed as another factor for decreased phagocytosis rates. For comparison, the authors studied the cellular adhesion of DC and Mζ to PLL-g-PEG coated microscopy slides. Remarkably, DC and Mζ were found to adhere to relatively protein-resistant PLL-g-PEG adlayers, whereas phagocytosis of microspheres coated with the same copolymers was inefficient. Overall, PLL(20)-[3.5]-PEG(2) was identified as the optimal copolymer to ensure resistance to both phagocytosis and cell adhesion. Finally, the authors studied coatings made from binary mixtures of PLL-g-PEG type copolymers that led to microspheres with combined properties. This enables future studies on cell targeting with ligand modified copolymers.

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“…Many studies now report that particles with diameters in both the nanometre and the micrometre range cross the small intestinal mucosal barrier and travel to other body sites (Volkheimer and Schultz, 1968;O'Hagan, 1990;Florence, 1997;Shreedhar et al, 2003;Keegan et al, 2003). Although the proportion of administered microparticles taken up may be low, the uptake of even small numbers of particles in this size range may have implications for human health in a variety of areas, such as drug or vaccine delivery, toxicology and immunology.…”

Section: Introductionmentioning

confidence: 99%

Effect of reproductive status on uptake of latex microparticles in rat small intestine

et al. 2005

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Biomimetic design in microparticulate vaccines

Cited by 29 publications

References 58 publications

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) particles

Phagocytosis of poly(L-lysine)-graft-poly (ethylene glycol) coated microspheres by antigen presenting cells: Impact of grafting ratio and poly (ethylene glycol) chain length on cellular recognition

Effect of reproductive status on uptake of latex microparticles in rat small intestine

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