Effect of cholesterol on the release of amphotericin B from PEG-Phospholilpid micelles

被引：37

作者：

Vakil, Ronak ^{[1
]}

Kwon, Glen S. ^{[1
]}

机构：

[1] Univ Wisconsin, Sch Pharm, Dept Pharmaceut Sci, Madison, WI 53705 USA

来源：

MOLECULAR PHARMACEUTICS | 2008年 / 5卷 / 01期

关键词：

PEG-lipid; cholesterol; micelle; condensing effect; polyene macrolide; amphotericin B; drug delivery; serum albumin; in vitro release;

D O I：

10.1021/mp700081v

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Micelles formed from PEG-DSPE solubilize high levels of the poorly water-soluble antifungal amphotericin B (AmB). AmB release from PEG-DSPE micelles is slow in buffer but remarkably rapid in the presence of bovine serum albumin (BSA). Sequential changes in the absorbance spectrum of AmB in PEG-DSPE micelles point to a rapid dissociation of incorporated drug in the presence of BSA. In this context, we have studied micelles formed from PEG-DSPE which coincorporate cholesterol (PEG-DSPElcholesterol). H-1 NMR measurements point to a lower mobility of lipid in PEG-DSPElcholesterol micelles compared to PEG-DSPE micelles. The absorbance spectrum of AmB incorporated in PEG-DSPElcholesterol micelles is distinct from that in PEG-DSPE micelles, which may point to differences in the drug-micelle interaction. AmB release from PEG-DSPElcholesterol micelles is slow in buffer and in the presence of BSA. The absorption spectrum of AmB in PEG-DSPElcholesterol micelles remained unchanged in BSA, further supporting stable incorporation and the slow release from the carrier.

引用

页码：98 / 104

页数：7

共 30 条

[1] Relative aggregation state and hemolytic activity of amphotericin B encapsulated by poly(ethylene oxide)-block-poly(N-hexyl-L-aspartamide)-acyl conjugate micelles:: effects of acyl chain length [J].

Adams, ML ;

Kwon, GS .

JOURNAL OF CONTROLLED RELEASE, 2003, 87 (1-3) :23-32

[2]

Aramwit P, 2000, J PHARM SCI, V89, P1589, DOI 10.1002/1520-6017(200012)89:12<1589::AID-JPS10>3.3.CO

[3]

2-Y

[4] In vitro characterization of PEGylated phospholipid micelles for improved drug solubilization:: Effects of PEG chain length and PC incorporation [J].

Ashok, B ;

Arleth, L ;

Hjelm, RP ;

Rubinstein, I ;

Önyüksel, H .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2004, 93 (10) :2476-2487

[5] The effect of aggregation state of amphotericin-B on its interactions with cholesterol- or ergosterol-containing phosphatidylcholine monolayers [J].

Barwicz, J ;

Tancrede, P .

CHEMISTRY AND PHYSICS OF LIPIDS, 1997, 85 (02) :145-155

[6] INHIBITION OF THE INTERACTION BETWEEN LIPOPROTEINS AND AMPHOTERICIN-B BY SOME DELIVERY SYSTEMS [J].

BARWICZ, J ;

GAREAU, R ;

AUDET, A ;

MORISSET, A ;

VILLIARD, J ;

GRUDA, I .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1991, 181 (02) :722-728

[7] ANTIOXIDANT-STABILIZED AMPHOTERICIN-B [J].

BEGGS, WH .

DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 1983, 1 (04) :339-341

[8] Molecular and mesoscopic properties of hydrophilic polymer-grafted phospholipids mixed with phosphatidylcholine in aqueous dispersion:: Interaction of dipalmitoyl N-poly(ethylene glycol) phosphatidylethanolamine with dipalmitoylphosphatidylcholine studied by spectrophotometry and spin-label electron spin resonance [J].

Belsito, S ;

Bartucci, R ;

Montesano, G ;

Marsh, D ;

Sportelli, L .

BIOPHYSICAL JOURNAL, 2000, 78 (03) :1420-1430

[9] ONE-SIDED ACTION OF AMPHOTERICIN-B ON CHOLESTEROL-CONTAINING MEMBRANES IS DETERMINED BY ITS SELF-ASSOCIATION IN THE MEDIUM [J].

BOLARD, J ;

LEGRAND, P ;

HEITZ, F ;

CYBULSKA, B .

BIOCHEMISTRY, 1991, 30 (23) :5707-5715

[10] Carrier effects on biological activity of amphotericin B [J].

Brajtburg, J ;

Bolard, J .

CLINICAL MICROBIOLOGY REVIEWS, 1996, 9 (04) :512-+

← 1 2 3 →