Intracellular disposition of polysaccharides in rat liver parenchymal and nonparenchymal cells

Tanaka, Tetsuro; Fujishima, Yuko; Hanano, Shinya; Kaneo, Yoshiharu

doi:10.1016/j.ijpharm.2004.07.031

Cited by 52 publications

(23 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Stereochemical configuration resulting from branching and hydroxyl group positions is a key factor in intracellular disposition. 4) Binding parameters, the number of binding sites (n), and the association constant (K a ) were estimated.…”

Section: Discussionmentioning

confidence: 99%

“…Polysaccharides, such as arabinogalactan, pullulan, dextran, and mannan, were bound and taken up by rat liver parenchymal cells specifically and/or nonspecifically. 4) For arabinogalactan, the nonspecific process was represented by a zero-order kinetic model. 7) We represented the pullulan uptake process in cultured rat liver parenchymal cells as involving two types of pathways, specific and nonspecific (Chart 1).…”

Section: Discussionmentioning

confidence: 99%

“…4) Briefly, pullulan was dissolved in 10% acetone in water and cooled in an ice bath. Then, 10% CNBr in acetone was added and the mixture stirred for 2 min.…”

Section: Methodsmentioning

confidence: 99%

“…4) In this study, we examined the uptake of pullulan, including the binding process followed by internalization in cultured rat liver parenchymal cells, and discuss the possibility of pullulan as a passive or active drug carrier via receptor mediated endocytosis (RME).…”

Section: 2)mentioning

confidence: 99%

See 3 more Smart Citations

Uptake of Pullulan in Cultured Rat Liver Parenchymal Cells

Tanaka

Hamano

Fujishima

et al. 2005

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Polysaccharides are an attractive drug carrier directed to the liver because they are distributed in the liver after intravenous injection. Pullulan is a polysaccharide consisting of three a-1,4-linked glucose molecules, polymerized by a-1,6-linkages to the terminal glucose, and has been employed as a carrier of human interferon-b and plasmid DNA to the liver. 1,2) We previously investigated the biodisposition of pullulan in rats and demonstrated that the asialoglycoprotein receptor (ASGPR) contributes to hepatic distribution.3) Furthermore, intracellular disposition of polysaccharides has been examined in rat liver parenchymal and nonparenchymal cells and studies have shown that binding and internalization to parenchymal cells was inhibited by asialofetuin, indicating that ASGPR is involved in the intracellular disposition of pullulan. 4)In this study, we examined the uptake of pullulan, including the binding process followed by internalization in cultured rat liver parenchymal cells, and discuss the possibility of pullulan as a passive or active drug carrier via receptor mediated endocytosis (RME). MATERIALS AND METHODSMaterials Pullulan (MW 58200) was supplied by Kuraray (Japan). Arabinogalactan and asialofetuin were purchased from Sigma (St. Louis, MO. U.S.A.). Fluorescein isothiocyanate was obtained from Wako Pure Chemical (Osaka, Japan). All other reagents were the highest grade commercially available.Radio-Labeling of Pullulan The tyramine derivative of pullulan was prepared according to a previous report. 4)Briefly, pullulan was dissolved in 10% acetone in water and cooled in an ice bath. Then, 10% CNBr in acetone was added and the mixture stirred for 2 min. Tetraethylamine in acetone was added to the solution. After 2 min, tyramine in 0.1 M NaHCO 3 containing 0.5 M NaCl was added and the reaction mixture stirred overnight at 4°C. The mixture was dialyzed against water and the macromolecular fraction obtained as a white powder. Animals Wistar male rats (6 weeks old) were purchased from Japan SLC, Inc. (Shizuoka, Japan). The rats were maintained on a commercially balanced stock diet (Oriental Yeast Co. Ltd., Tokyo, Japan) with water ad libitum. Before experimentation, each rat was anesthetized with pentobarbital. All aspects of the study were performed according to the Fukuyama University guidelines for animal experiments.Isolation and Culture of Rat Liver Parenchymal Cells Hepatocytes were isolated from male Wistar rats (7 weeks old) by the collagenase perfusion method.6) The hepatocytes were centrifuged at 50ϫg and the resulting pellet washed with Hanks' medium containing 2.4 mM CaCl 2 and 10 mM HEPES (pH 7.4). The cells were fractionated on Percoll density gradients, which resulted in a greater than 98% viability, as verified by a trypan blue exclusion test. The cells were then resuspended in William's Medium E containing dexamethasone (1 µM), insulin (0.1 µM), and 10% FBS. The cells (1ϫ10 6 cells) were plated in a 35-mm collagen type I coated culture dish (Iwaki, Funabashi, Japan) and incubated in hu...

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

“…4) Briefly, pullulan was dissolved in 10% acetone in water and cooled in an ice bath. Then, 10% CNBr in acetone was added and the mixture stirred for 2 min.…”

Section: Methodsmentioning

confidence: 99%

Section: 2)mentioning

confidence: 99%

See 2 more Smart Citations

Uptake of Pullulan in Cultured Rat Liver Parenchymal Cells

Tanaka

Hamano

Fujishima

et al. 2005

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…Additionally, polysaccharides can inherently recognize specific receptors located on tumor cells thus conveying targeting properties. Tumorotropic properties can be also conveyed by altering the chemical structure, namely polymer size, charge, and by introducing targeting moieties [19][20][21]. Therefore, the combination of structural and biological properties of polysaccharides, together with the possibility of chemical modification by simple procedures, makes these materials suitable candidates for development of soluble conjugates for anticancer drug delivery.…”

Section: Introductionmentioning

confidence: 99%

Polysaccharide-Based Anticancer Prodrugs

Caliceti

Salmaso

Bersani

2009

Macromolecular Anticancer Therapeutics

View full text Add to dashboard Cite

So far, polysaccharides have been widely used in pharmaceutical technology as first choice excipients for production of traditional formulations. Nevertheless, in the recent years these natural and semisynthetic macromolecules have been addressed for new challenging applications as functional materials for innovative formulations. Their peculiar physicochemical and biological properties have been exploited to develop macromolecular prodrugs which can exhibit favorable biopharmaceutical properties and enforce the therapeutic performance of the parent drugs. These polymers display, in fact, high biocompatibility and biodegradability, multiple insertion points, and biological properties that can be advantageously exploited in drug delivery. In particular, the multifunctional structures of these polymers are anchoring points for conjugation of several anticancer drugs, which usually suffer from poor physicochemical, biopharmaceutical, and therapeutic properties that limit their therapeutic performance and proper use in anticancer treatment. Polysaccharide-based anticancer prodrugs can be designed to endow derivatives with new bioresponse, targeting, or environmental triggering properties or to combine molecules with synergistic therapeutic effect. Over the years, a variety of synthetic protocols have been set up to conjugate anticancer drugs to the polysaccharide backbone via specific linkages or through spacers which convey to the conjugates selective drug-delivery properties. Furthermore, the intrinsic antitumor activity and cell-targeting properties of few polysaccharides represent an additional value to the final therapeutic systems. Anticancer drugs with different pharmacodynamic, pharmacokinetic, and physicochemical properties have been successfully conjugated to various natural and semisynthetic polysaccharides highlighting the interesting perspectives for exploitation of new promising anticancer polymer therapeutics.

show abstract

Integrated Development of Glycobiologics: from Discovery to Applications in the Design of Nanoparticular Drug Delivery Systems

Vauthier

Bertholon

Labarre

2010

Pharmaceutical Sciences Encyclopedia

View full text Add to dashboard Cite

From the three major classes of biomolecules including proteins, nucleic acids and carbohydrates, the carbohydrates are, at the moment, the least exploited. The recent development of operating methods for the analysis of carbohydrates and for the synthesis of oligosaccharides supports the efforts made to investigate the roles of carbohydrates in biological phenomena. Research on carbohydrates is very active leading to discovery of new oligosaccharides and functions almost everyday as witnesses by the amount of papers published every month. The purpose of this chapter is to point out some of the functions of carbohydrates that have been identified and that may be interesting to integrate within the design of nanoparticulate drug carriers able to carry and target a drug to the diseased organs or cells. The complete control of the biodistribution of these systems which is mainly governed by their surface properties remains one of the major challenges to achieve. Among the different strategies proposed so far, it has been suggested to coat the nanoparticulate drug carriers with polysaccharides in order to mimic the surface of cells, bacteria or viruses and to confer the nanoparticles new surface properties including the biological activities of the carbohydrates. The coating of nanoparticulate drug carriers with certain types of carbohydrates may be interesting to give the nanoparticles specific recognition or signalling functions to improve their targeting specificity and efficiency. Other carbohydrates display very specific biological activities that may be interesting to combine with nanoparticulate drug carriers to create biologically active nanoparticulate systems. Many other examples will be discussed in this chapter and the benefit of the approach will be examined with the few examples of nanoparticulate drug carriers already developed on this basis.

show abstract

Intracellular disposition of polysaccharides in rat liver parenchymal and nonparenchymal cells

Cited by 52 publications

References 24 publications

Uptake of Pullulan in Cultured Rat Liver Parenchymal Cells

Uptake of Pullulan in Cultured Rat Liver Parenchymal Cells

Polysaccharide-Based Anticancer Prodrugs

Integrated Development of Glycobiologics: from Discovery to Applications in the Design of Nanoparticular Drug Delivery Systems

Contact Info

Product

Resources

About