caa a22 4500 477128475 CHVBK 20180405111656.0 cr unu---uuuuu 170330e19971101xx s 000 0 eng 10.1023/A:1012126301290 doi (NATIONALLICENCE)springer-10.1023/A:1012126301290 The Mechanism of Uptake of Biodegradable Microparticles in Caco-2 Cells Is Size Dependent [Elektronische Daten] [Manisha Desai, Vinod Labhasetwar, Elke Walter, Robert Levy, Gordon Amidon] Purpose. To study the uptake of biodegradable microparticles in Caco-2 cells. Methods. Biodegradable microparticles of polylactic polyglycolic acid co-polymer (PLGA 50:50) of mean diameters 0.1 μm, 1 μm, and 10 μm containing bovine serum albumin as a model protein and 6-coumarin as a fluorescent marker were formulated by a multiple emulsion technique. The Caco-2 cell monolayers were incubated with each diameter microparticles (100 μg/ml) for two hours. The microparticle uptake in Caco-2 cells was studied by confocal microscopy and also by quantitating the 6-coumarin content of the microparticles taken up by the cells. The effects of microparticle concentration, and incubation time and temperature on microparticle cell uptake were also studied. Results. The study demonstrated that the Caco-2 cell microparticle uptake significantly depends upon the microparticle diameter. The 0.1 μm diameter microparticles had 2.5 fold greater uptake on the weight basis than the 1 μm and 6 fold greater than the 10 μm diameter microparticles. Similarly in terms of number the uptake of 0.1 μm diameter microparticles was 2.7 × 103 fold greater than the 1 μm and 6.7 × 106 greater than the 10 μm diameter microparticles. The efficiency of uptake of 0.1 μm diameter microparticles at 100 μg/ml concentration was 41% compared to 15% and 6% for the 1 μm and the 10 μm diameter microparticles, respectively. The Caco-2 cell microparticle (0.1 μm) uptake increased with concentration in the range of 100 μg/ml to 500 μg/ml which then reached a plateau at higher concentration. The uptake of microparticles increased with incubation time, reaching a steady state at two hours. The uptake was greater at an incubation temperature of 37°C compared to at 4°C. Conclusions. The Caco-2 cell microparticle uptake was microparticle diameter, concentration, and incubation time and temperature dependent. The small diameter microparticles (0.1 μm) had significantly greater uptake compared to larger diameter microparticles. The results thus suggest that the mechanism of uptake of microparticles in Caco-2 cell is particle diameter dependent. Caco-2 cells are used as an in vitro model for gastrointestinal uptake, and therefore the results obtained in these studies could be of significant importance in optimizing the microparticle-based oral drug delivery systems. Plenum Publishing Corporation, 1997 drug carrier nationallicence oral drug delivery nationallicence vaccine nationallicence absorption nationallicence bioavailability nationallicence endocytosis nationallicence Desai Manisha College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut Labhasetwar Vinod College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut Walter Elke College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut Levy Robert College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut Amidon Gordon College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1568-1573 0724-8741 14:11<1568 1997 14 11095 https://doi.org/10.1023/A:1012126301290 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012126301290 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Desai Manisha College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut NATIONALLICENCE 700 1- Labhasetwar Vinod College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut NATIONALLICENCE 700 1- Walter Elke College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut NATIONALLICENCE 700 1- Levy Robert College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut NATIONALLICENCE 700 1- Amidon Gordon College of Pharmacy, University of Michigan, 48109, Ann Arbor, Michigan aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/11(1997-11-01), 1568-1573 0724-8741 14:11<1568 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer