Lysosome membrane permeability: implications for drug delivery

被引:73
作者
Lloyd, JB [1 ]
机构
[1] Univ Sunderland, Inst Pharm & Chem, Sunderland SRS 3SD, Durham, England
关键词
lysosomes; membrane permeability; drug delivery;
D O I
10.1016/S0169-409X(99)00065-4
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The membrane of the lysosome contains substrate-specific porters for a wide range of metabolites. Their physiological role is in promoting the efflux of the products of intralysosomal catabolism. With few exceptions, the specificity of these porters makes them unlikely candidates for the translocation of xenobiotics across the lysosome membrane. Where efflux from the lysosome is possible, it is likely to be accomplished by passive diffusion. Experimental studies on passive diffusion across the lysosome membrane have shown that its characteristics are similar to those of other biological membranes. Ease of permeation decreases with increasing hydrophilicity. Macromolecules and some highly hydrophilic molecules as small as sucrose are effectively non-permeant. The notional hydrogen-bonding capacity of molecules (an inverse correlate of oil:water partition coefficient) has been found a good predictor of permeance. Predictions of ease of permeation across lysosome membranes is of value when drug delivery strategies are contemplated that involve a drug-conjugate reaching the lysosome compartment and drug release there by the lysosomal enzymes. These strategies will be unsuccessful if the drug is unable to leave the lysosome and reach the cellular sites where its pharmacological action is required. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:189 / 200
页数:12
相关论文
共 36 条
[1]   Lysosome membrane permeability to amines [J].
Andrew, CL ;
Klemm, AR ;
Lloyd, JB .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 1997, 1330 (01) :71-82
[2]  
ASHWELL G, 1974, ADV ENZYMOL RAMB, V41, P99
[3]   TISSUE FRACTIONATION STUDIES .2. THE NATURE OF THE LINKAGE BETWEEN ACID PHOSPHATASE AND MITOCHONDRIA IN RAT-LIVER TISSUE [J].
BERTHET, J ;
BERTHET, L ;
APPELMANS, F ;
DEDUVE, C .
BIOCHEMICAL JOURNAL, 1951, 50 (02) :182-189
[4]   Cellular uptake and release of two contrasting iron chelators [J].
Cable, H ;
Lloyd, JB .
JOURNAL OF PHARMACY AND PHARMACOLOGY, 1999, 51 (02) :131-134
[5]   UPTAKE STORAGE AND INTRACELLULAR HYDROLYSIS OF CARBOHYDRATES BY MACROPHAGES [J].
COHN, ZA ;
EHRENREICH, BA .
JOURNAL OF EXPERIMENTAL MEDICINE, 1969, 129 (01) :201-+
[6]  
DEDUVE C, 1974, BIOCHEM PHARMACOL, V23, P2395
[7]  
DEDUVE C, 1969, LYSOSOMES BIOLOGY PA, V1, P3
[8]  
DEDUVE C, 1968, INTERACTION DRUGS SU, P155
[9]   BIOLOGICAL MEMBRANES - PHYSICAL BASIS OF ION AND NONELECTROLYTE SELECTIVITY [J].
DIAMOND, JM ;
WRIGHT, EM .
ANNUAL REVIEW OF PHYSIOLOGY, 1969, 31 :581-+
[10]   ANTICANCER AGENTS COUPLED TO N-(2-HYDROXYPROPYL)METHACRYLAMIDE COPOLYMERS .2. EVALUATION OF DAUNOMYCIN CONJUGATES INVIVO AGAINST L1210 LEUKEMIA [J].
DUNCAN, R ;
KOPECKOVA, P ;
STROHALM, J ;
HUME, IC ;
LLOYD, JB ;
KOPECEK, J .
BRITISH JOURNAL OF CANCER, 1988, 57 (02) :147-156