Specific targeting of a lipophilic prodrug of iododeoxyuridine to parenchymal liver cells using lactosylated reconstituted high density lipoprotein particles

Bijsterbosch, Martin K.; Bilt, Hendrika Van De; Berkel, Theo J.C. Van

doi:10.1016/0006-2952(96)00170-0

Cited by 32 publications

(19 citation statements)

References 30 publications

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“…This effect is mainly attributed to thermodynamic properties of multivalent ligands (comparable to the chelate effect) rather than to the presence of multiple receptor binding sites. Various carriers, [77,78] drug conjugates, [79][80][81][82][83][84] and imaging agents [85] with partly remarkable binding constants for the ASGPR have been investigated during the past years.…”

Section: Active Targetingmentioning

confidence: 99%

Prodrug Strategies in Anticancer Chemotherapy

Kratz¹,

Müller²,

Ryppa³

et al. 2008

ChemMedChem

438

425

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The majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor-specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor-specific characteristics such as low pH or the expression of tumor-associated enzymes. Furthermore, other strategies such as ADEPT (antibody-directed enzyme prodrug therapy) and the design of self-eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.

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Section: Active Targetingmentioning

confidence: 99%

Prodrug Strategies in Anticancer Chemotherapy

Kratz¹,

Müller²,

Ryppa³

et al. 2008

ChemMedChem

438

425

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“…Similar to LDL, compounds intended for HDL core-loading must be hydrophobic and contain an unsaturated hydrocarbon chain (>10 carbons) or a sterol ester moiety. Several examples of synthetic HDL reconstituted with drug or imaging probes have been described [58][59][60].…”

Section: Core-loading "Reconstitution" Proceduresmentioning

confidence: 99%

Lipoprotein‐Based Nanoplatforms for Cancer Molecular Imaging

Corbin

Zheng

2011

Nanoplatform‐Based Molecular Imaging

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LIPOPROTEINS: NATURE'S ENDOGENOUS NANOCARRIEREfficient transport of key lipids, such as triacylglycerols (TAGs) and cholesterol, is an essential process in mammalian systems. These molecules respectively serve as a high-energy fuel source and as a structural building block for all cells. Like other essential nutrients and substrates these molecules must be delivered to cells through the blood. The hydrophobicity of these molecules, however, poses a daunting problem for their transport through the aqueous channels of the vascular system. Nature has uniquely addressed this dilemma through the lipoprotein carrier system. Plasma lipoproteins are macromolecular vehicles that transport neutral lipids (fat and cholesterol) through the circulatory system and extracellular fluid compartments of the body. These spherical emulsion-like complexes display a range of physicochemical properties; however, they have a common structural organization ( Fig. 18.1.) consisting of an apolar core of TAG and cholesterol esters surrounded by a monolayer of phospholipids and free cholesterol. Interspersed across the phospholipid monolayer are specific amphipathic proteins (apolipoproteins) whose hydrophilic domains extend toward the aqueous environment. These apolipoproteins act to stabilize and confer structural framework to the lipoproteins, modulate enzyme activity, as well as serve as receptor ligands for the lipoprotein delivery system [1]. Nanoplatform-Based Molecular Imaging Edited by Xiaoyuan ChenPlasma lipoproteins can be designated into various classes based on numerous physical parameters (e.g., electrophoretic mobility, diameter). The most commonly accepted classification is based on the density of the different lipoprotein species (see Table 18.1). According to this classification scheme the major density categories include the following.(1) Chylomicrons (d < 0.95 g/mL) are TAG-rich emulsions particles (80-88% by weight) that are synthesized by the intestine after a fatty meal. Chylomicrons are the largest particles in the lipoprotein family (80 nm to 1 m in diameter) and have the highest lipid-to-protein ratio.(2) Very low density lipoproteins (d = 0.95-1.006 g/mL) are also TAG-rich particles, however, they are synthesized by the liver. They are smaller than chylomicrons (30-80 nm in diameter) and contain relatively less TAG but more cholesterol and protein.(3) Low density lipoproteins (d = 1.020-1.063 g/mL) are particles formed from the intravascular catabolism of VLDLs. The LDL core is predominantly cholesterol ester molecules. Finally, (4) high density lipoproteins (d = 1.063-1.210 g/mL) These carriers are the smallest (6-12 nm in diameter) member of the lipoprotein family. Their core is mainly composed of cholesterol esters and they are composed of a relatively high proportion of protein (35-56% by weight).

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“…13) The change of the drug amount in tissue with time can be described as follows: (1) where T(t) is the amount of drugs in 1 g tissue, C(t) is the blood concentration of drugs, Cl in is the tissue uptake rate index (clearance) from blood to tissue, and K out is the efflux rate constant from the tissues. To estimate the uptake rate index, distribution in the first 30 min after intravenous administration was measured, allowing the contribution of efflux processes and metabolism to be ignored.…”

Section: Drug Distribution Ratio Between Blood Cells To Plasmamentioning

confidence: 99%

“…Recently, the use of high-density lipoprotein, 1) low-density lipoprotein (LDL), 2,3) liposomes, 4,5) and lipid emulsions 5) as drug carriers have been focused on to control drug delivery. However, it is difficult to load hydrophilic drugs to these hydrophobic carriers because of their poor affinity.…”

mentioning

confidence: 99%