TY - JOUR
T1 - Relating the phagocytosis of microparticles by alveolar macrophages to surface chemistry
T2 - The effect of 1,2-dipalmitoylphosphatidylcholine
AU - Evora, Carmen
AU - Soriano, Isabel
AU - Rogers, Rick A.
AU - Shakesheff, Kevin M.
AU - Hanes, Justin
AU - Langer, Robert
N1 - Funding Information:
Financial support was provided by NIH grant 454-HD29125. Individual support was provided to Carmen Evora and Isabel Soriano by the DGICYT of the Spanish Science and Education Ministry (R1-P3300) and by the DGUI of the Canary Government, respectively. Kevin Shakesheff acknowledges the support of the NATO Fellowship for North America. Rick Rogers acknowledges support from HL4350, NIH 33009. We thank the expert technical assistance of Jean Lai, Kafi Meadows, Emily Sullivan and Dr. James Ontonini.
PY - 1998/2/12
Y1 - 1998/2/12
N2 - This study examines the potential of 1,2-dipalmitoylphosphatidylcholine (DPPC), a major component of lung surfactant, to reduce the phagocytosis of microspheres by altering the cellular interactions occurring in the alveoli. These microspheres could be designed to act as a controlled delivery system for small molecules, peptides or proteins for pulmonary administration. Microspheres were prepared using poly(lactic-co-glycolic acid) (PLGA, 50/50) and encapsulated peroxidase as a model protein. DPPC was included in some formulations. The interaction of PLGA and DPPC-PLGA microspheres with phagocytic cells was evaluated using lung macrophages in culture. X-ray Photoelectron Spectra (XPS) results indicate that the inclusion of DPPC in the microspheres alters the microsphere surface chemistry, with the DPPC covering a large portion of the microsphere surface. The dominance of DPPC on the microsphere surface is highly beneficial in moderating the interactions occurring between the microspheres and phagocytic cells in the lung. Fluorescent confocal microscopy indicates that only 25% of cells internalized DPPC-coated particles, whereas 70% of those cells exposed to particles without the DPPC coating internalized particles after one hour of incubation.
AB - This study examines the potential of 1,2-dipalmitoylphosphatidylcholine (DPPC), a major component of lung surfactant, to reduce the phagocytosis of microspheres by altering the cellular interactions occurring in the alveoli. These microspheres could be designed to act as a controlled delivery system for small molecules, peptides or proteins for pulmonary administration. Microspheres were prepared using poly(lactic-co-glycolic acid) (PLGA, 50/50) and encapsulated peroxidase as a model protein. DPPC was included in some formulations. The interaction of PLGA and DPPC-PLGA microspheres with phagocytic cells was evaluated using lung macrophages in culture. X-ray Photoelectron Spectra (XPS) results indicate that the inclusion of DPPC in the microspheres alters the microsphere surface chemistry, with the DPPC covering a large portion of the microsphere surface. The dominance of DPPC on the microsphere surface is highly beneficial in moderating the interactions occurring between the microspheres and phagocytic cells in the lung. Fluorescent confocal microscopy indicates that only 25% of cells internalized DPPC-coated particles, whereas 70% of those cells exposed to particles without the DPPC coating internalized particles after one hour of incubation.
KW - Biodegradable polymers
KW - Lung delivery
KW - Macrophages
KW - Microspheres
KW - Phagocytosis
KW - Proteins
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U2 - 10.1016/S0168-3659(97)00149-1
DO - 10.1016/S0168-3659(97)00149-1
M3 - Article
C2 - 9685911
AN - SCOPUS:0032509910
VL - 51
SP - 143
EP - 152
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 2-3
ER -