Relating the phagocytosis of microparticles by alveolar macrophages to surface chemistry: the effect of 1,2-dipalmitoylphosphatidylcholine

被引:125
作者
Evora, C
Soriano, I
Rogers, RA
Shakesheff, KM
Hanes, J
Langer, R
机构
[1] MIT, Dept Chem Engn, Cambridge, MA 02139 USA
[2] Univ La Laguna, Fac Farm, Dept Ingn Quim & Tecnol Farmaceut, La Laguna 38200, Spain
[3] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA
关键词
microspheres; proteins; lung delivery; phagocytosis; macrophages; biodegradable polymers;
D O I
10.1016/S0168-3659(97)00149-1
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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. (C) 1998 Elsevier Science BN.
引用
收藏
页码:143 / 152
页数:10
相关论文
共 28 条
[1]   PULMONARY DELIVERY OF PEPTIDE DRUGS - EFFECT OF PARTICLE-SIZE ON BIOAVAILABILITY OF LEUPROLIDE ACETATE IN HEALTHY MALE-VOLUNTEERS [J].
ADJEI, A ;
GARREN, J .
PHARMACEUTICAL RESEARCH, 1990, 7 (06) :565-569
[2]  
BYRON P R, 1990, Advanced Drug Delivery Reviews, V5, P107, DOI 10.1016/0169-409X(90)90010-P
[3]   THE PHARMACOKINETICS OF PULMONARY-DELIVERED INSULIN - A COMPARISON OF INTRATRACHEAL AND AEROSOL ADMINISTRATION TO THE RABBIT [J].
COLTHORPE, P ;
FARR, SJ ;
TAYLOR, G ;
SMITH, IJ ;
WYATT, D .
PHARMACEUTICAL RESEARCH, 1992, 9 (06) :764-768
[4]   RESORBABLE POLYMERIC MICROSPHERES FOR DRUG-DELIVERY - PRODUCTION AND SIMULTANEOUS SURFACE MODIFICATION USING PEO-PPO SURFACTANTS [J].
COOMBES, AGA ;
SCHOLES, PD ;
DAVIES, MC ;
ILLUM, L ;
DAVIS, SS .
BIOMATERIALS, 1994, 15 (09) :673-680
[5]   Inhalation therapy with recombinant human deoxyribonuclease I [J].
Gonda, I .
ADVANCED DRUG DELIVERY REVIEWS, 1996, 19 (01) :37-46
[6]   BIODEGRADABLE LONG-CIRCULATING POLYMERIC NANOSPHERES [J].
GREF, R ;
MINAMITAKE, Y ;
PERACCHIA, MT ;
TRUBETSKOY, V ;
TORCHILIN, V ;
LANGER, R .
SCIENCE, 1994, 263 (5153) :1600-1603
[7]  
Gupta PK, 1990, PHARM RES, V7, pS82
[8]  
HANES J, UNPUB POLY DL LACTIC
[9]   INFLUENCE OF SURFACE COVERAGE WITH POLY(ETHYLENE OXIDE) ON ATTACHMENT OF STERICALLY STABILIZED MICROSPHERES TO RAT KUPFFER CELLS IN-VITRO [J].
HARPER, GR ;
DAVIS, SS ;
DAVIES, MC ;
NORMAN, ME ;
TADROS, TF ;
TAYLOR, DC ;
IRVING, MP ;
WATERS, JA ;
WATTS, JF .
BIOMATERIALS, 1995, 16 (06) :427-439
[10]   THE ORGAN DISTRIBUTION AND CIRCULATION TIME OF INTRAVENOUSLY INJECTED COLLOIDAL CARRIERS STERICALLY STABILIZED WITH A BLOCKCOPOLYMER - POLOXAMINE 908 [J].
ILLUM, L ;
DAVIS, SS ;
MULLER, RH ;
MAK, E ;
WEST, P .
LIFE SCIENCES, 1987, 40 (04) :367-374