Lysosome membrane permeability: implications for drug delivery

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 spec ificity of these porters makes them unlikely candidates for the translocati on of xenobiotics across the lysosome membrane. Where efflux from the lysos ome is possible, it is likely to be accomplished by passive diffusion. Expe rimental studies on passive diffusion across the lysosome membrane have sho wn that its characteristics are similar to those of other biological membra nes. Ease of permeation decreases with increasing hydrophilicity. Macromole cules and some highly hydrophilic molecules as small as sucrose are effecti vely 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 i nvolve a drug-conjugate reaching the lysosome compartment and drug release there by the lysosomal enzymes. These strategies will be unsuccessful if th e drug is unable to leave the lysosome and reach the cellular sites where i ts pharmacological action is required. (C) 2000 Elsevier Science B.V. All r ights reserved.