Influence of surface chemistry of poly(amidoamine) dendrimers on Caco-2 cell monolayers

被引:41
作者
El-Sayed, M
Ginski, M
Rhodes, CA
Ghandehari, H
机构
[1] Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA
[2] Guilford Pharmaceut Inc, Dept Pharmaceut, Baltimore, MD 21224 USA
关键词
poly(amidoamine) dendrimers; water-soluble polymers; Caco-2; cells; transepithelial transport; oral drug delivery;
D O I
10.1177/0883911503018001002
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The objective of this research was to investigate the effect of surface charge of poly(amidoamine), PAMAM, dendrimers on the integrity, paracellular permeability, and viability of Caco-2 cell monolayers by monitoring the transepithelial electrical resistance (TEER), mannitol permeability, and leakage of lactate dehydrogenase (LDH) enzyme, respectively. Neutral PAMAM-OH, generations 2-4 (G2-G4), and anionic PAMAM-COOH (G-0.5-G4.5) dendrimers were incubated with Caco-2 cell monolayers at donor concentrations of 0.1, 1.0, and 10.0 mM for 90, 150, and 210 min. Neutral G2-G4 and anionic G-0.5, G0.5, G1.5 and G4.5 dendrimers did not cause any significant change in TEER or mannitol permeability across Caco-2 cell monolayers. Anionic G2.5 and G3.5 dendrimers, however, caused an incubation time-dependant decline in TEER values and up to a 6-fold increase in mannitol permeability. All anionic PAMAM-COOH dendrimers caused an incubation time-, concentration-, and generation-dependant LDH leakage that was not observed with neutral PAMAM-OH dendrimers. These studies suggest a size and/or charge "window" where anionic dendrimers may enhance paracellular transport across Caco-2 cell monolayers further confirming their potential as drug carriers and permeation enhancers for oral drug delivery.
引用
收藏
页码:7 / 22
页数:16
相关论文
共 23 条
[1]  
[Anonymous], 1993, ALDRICHIM ACTA
[2]   Mucoadhesive polymers as platforms for peroral peptide delivery and absorption: synthesis and evaluation of different chitosan-EDTA conjugates [J].
Bernkop-Schnurch, A ;
Krajicek, ME .
JOURNAL OF CONTROLLED RELEASE, 1998, 50 (1-3) :215-223
[3]   The potential of mucoadhesive polymers in enhancing intestinal peptide drug absorption .3. Effects of chitosan-glutamate and carbomer on epithelial tight junctions in vitro [J].
Borchard, G ;
Luessen, HL ;
deBoer, AG ;
Verhoef, JC ;
Lehr, CM ;
Junginger, HE .
JOURNAL OF CONTROLLED RELEASE, 1996, 39 (2-3) :131-138
[4]   In vitro myotoxicity of selected cationic macromolecules used in non-viral gene delivery [J].
Brazeau, GA ;
Attia, S ;
Poxon, S ;
Hughes, JA .
PHARMACEUTICAL RESEARCH, 1998, 15 (05) :680-684
[5]   Transepithelial transport of poly(amidoamine) dendrimers across Caco-2 cell monolayers [J].
El-Sayed, M ;
Ginski, M ;
Rhodes, C ;
Ghandehari, H .
JOURNAL OF CONTROLLED RELEASE, 2002, 81 (03) :355-365
[6]  
Fleisher D., 1995, PEPTIDE BASED DRUG D, P501
[7]  
Ghandehari H, 1997, J PHARMACOL EXP THER, V280, P747
[8]   Enhancement of paracellular drug transport with highly quaternized N-trimethyl chitosan chloride in neutral environments:: In vitro evaluation in intestinal epithelial cells (Caco-2) [J].
Kotzé, AF ;
Thanou, MM ;
Lueben, HL ;
de Boer, AG ;
Verhoef, JC ;
Junginger, HE .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1999, 88 (02) :253-257
[9]   Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2) [J].
Kotze, AF ;
Luessen, HL ;
de Leeuw, BJ ;
de Boer, BG ;
Verhoef, JC ;
Junginger, HE .
JOURNAL OF CONTROLLED RELEASE, 1998, 51 (01) :35-46
[10]   N-trimethyl chitosan chloride as a potential absorption enhancer across mucosal surfaces: In vitro evaluation in intestinal epithelial cells (Caco-2) [J].
Kotze, AF ;
Luessen, HL ;
deLeeuw, BJ ;
deBoer, BG ;
Verhoef, JC ;
Junginger, HE .
PHARMACEUTICAL RESEARCH, 1997, 14 (09) :1197-1202