Effects of cellulose derivatives and poly(ethylene oxide)-poly(propylene oxide) tri-block copolymers (Pluronic)surfactants) on the properties of alginate based microspheres and their interactions with phagocytic cells.
The goal of this study was to examine the phagocytosis of alginate based microspheres with different surface properties. Favorable interaction with macrophages is critical for uptake subsequent processing of the microspheres used for oral vaccine delivery. We examined the effects of size of alginate microspheres and hydrophobicity on cellular uptake. We also examined the toxicity of formulation components to phagocytic cells. Alginate microspheres were made by the emulsion-cross-linking technique. Five different formulations of microspheres were evaluated for size, hydrophobicity, cellular uptake and toxicity to macrophages. The formulations examined were: alginate alone (A), alginate with methylcellulose (AA) AA with Pluronic L61 (AA61), alginate with hydroxypropyl methylcellulose (AK3), and AK3 with Pluronic (L61 (AK3 61). Microspheres with without poly-L-lysine (PLL) coating were tested. The mean volume sizes of A, AA, AA61, AK3, AK3 61 microspheres (MS) were 11, 10.5, 3.8, 8.7 and 3.9 mocrom, respectively. After coating them with PLL the mean volume sizes were 10.4, 10, 3.7, 8.8 and 3.5 microm, respectively. Hydrophobicity of the microspheres was evaluated by measuring contact angle on a glass slide coated with the microspheres. The contact angles measured using a goniometer on A, AA, AA61, AK3, AK3 61 MS were 20, 34.8, 71, 29 and 80 degrees, respectively whereas those MS coated with PLL were 49.7, 55.8, 91, 48.25 and 84.4 degrees, respectively. Cellular uptake studies using flow cytometery revealed that AA61 MS coated with PLL were phagocytosed most often by mouse macrophages. There was no statistically significant difference in cellular uptake among those MS without PLL coating. Toxicity to macrophages was shown to depend on the ratio of microspheres to cells. These studies suggest that formulation can dramatically affect the physical characteristics of alginate MS in ways that can affect how they will interact with cells in the body when administered as a vaccine delivery system.
Kidane
Argaw
A
Pharmacia Corporation, Animal Health, 7923-190-353, 7000 Portage Road, Kalamazoo, MI 49001-0199, USA.
Guimond
Paul
P
Rob Ju
Tzu-chi
TC
Sanchez
Margaret
M
Gibson
Janet
J
North
Adam
A
HogenEsch
Harm
H
Bowersock
Terry L
TL
D000464:Alginates / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002460:Cell Line; D002478:Cells, Cultured; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008863:Microspheres; D010586:Phagocytes / Q000378:metabolism*; D010587:Phagocytosis / Q000187:drug effects; D020442:Poloxamer / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D011409:Propylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D020298:U937 Cells
D000464:Alginates; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D013501:Surface-Active Agents; D020442:Poloxamer; D011092:Polyethylene Glycols; D002482:Cellulose