Partitioning of prototropic species of an anticancer drug ellipticine in bile salt aggregates of different head groups and hydrophobic skeletons: a photophysical study to probe bile salts as multisite drug carriers

Background: Nanotechnology has contributed a great deal to the field of medical science. Smart drugdelivery vectors, combined with stimuli-based characteristics, are becoming increasingly important. The use of external and internal stimulating factors can have enormous benefits and increase the targeting efficiency of nanotechnology platforms. The pH values of tumor vascular tissues are acidic in nature, allowing the improved targeting of anticancer drug payloads using drug-delivery vectors. Nanopolymers are smart drug-delivery vectors that have recently been developed and recommended for use by scientists because of their potential targeting capabilities, non-toxicity and biocompatibility, and make them ideal nanocarriers for personalized drug delivery. Method: The present review article provides an overview of current advances in the use of nanoparticles (NPs) as anticancer drug-delivery vectors. Results: This article reviews the molecular basis for the use of NPs in medicine, including personalized medicine, personalized therapy, emerging vistas in anticancer therapy, nanopolymer targeting, passive and active targeting transports, pH-responsive drug carriers, biological barriers, computer-aided drug design, future challenges and perspectives, biodegradability and safety. Conclusions: This article will benefit academia, researchers, clinicians, and government authorities by providing a basis for further research advancements.

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STUDI VIABILITAS ISOLAT BAKTERI ASAM LAKTAT YANG DIISOLASI DARI ASINAN REBUNG BAMBU TABAH TERHADAP pH RENDAH DAN GARAM EMPEDU

JURNAL REKAYASA DAN MANAJEMEN AGROINDUSTRI ◽

10.24843/jrma.2019.v07.i01.p01 ◽

2019 ◽

Vol 7 (1) ◽

pp. 1 ◽

Cited By ~ 1

Author(s):

Nurul Octavia Wasis ◽

Nyoman Semadi Antara ◽

Ida Bagus Wayan Gunam

Keyword(s):

Lactic Acid ◽

Lactic Acid Bacteria ◽

Bile Salt ◽

Bile Salts ◽

Salt Resistance ◽

Low Ph ◽

Fermented Food ◽

Bamboo Shoot ◽

Probiotic Lactic Acid Bacteria ◽

Mrs Broth

Tabah bamboo shoot pickle is one of the fermented food which is the source of lactic acid bacteria. Lactic acid bacteria (LAB) is beneficial to health because it has the ability as a probiotic. Lactic acid bacteria that have probiotic criteria should have resistance to low pH and bile salts. This study aims to determine isolates of lactic acid bacteria isolated from tabah bamboo shoot pickle resistant to low pH and bile salts (NaDC). Lactic acid bacteria were tested to low pH by using MRS broth that have different pH (pH 2, pH 3, pH 4 and pH 6.2 as a control) incubated at 37ºC for 3 hours. isolates were survive in low pH then continued in bile salt resistance test with 0.3% bile salt concentration for 15 minutes, 30 minutes, 45 minutes, 60 minutes and 24 hours. The results showed that three isolates out of 88 isolates had ability to grow in low pH and in medium supplemented by NaDC 0,3%. The isolates are AR 3057, AR 3101 and AR 6152 which can be used as candidat of probiotic. Keywords : Tabah bamboo shoot pickle, lactic acid bacteria, probiotic, low pH, bile salt

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Regulation of mdr2 P-glycoprotein expression by bile salts

Biochemical Journal ◽

10.1042/bj3210389 ◽

1997 ◽

Vol 321 (2) ◽

pp. 389-395 ◽

Cited By ~ 39

Author(s):

Charles M. G. FRIJTERS ◽

Roelof OTTENHOFF ◽

Michel J. A. van WIJLAND ◽

Carin M. J. van NIEUWKERK ◽

Albert K. GROEN ◽

...

Keyword(s):

Bile Salt ◽

Bile Salts ◽

Control Diet ◽

Mrna Level ◽

Northern Blotting ◽

Mrna Levels ◽

Male Mice ◽

Complete Replacement ◽

P Glycoprotein ◽

Mrna Content

The phosphatidyl translocating activity of the mdr2 P-glycoprotein (Pgp) in the canalicular membrane of the mouse hepatocyte is a rate-controlling step in the biliary secretion of phospholipid. Since bile salts also regulate the secretion of biliary lipids, we investigated the influence of the type of bile salt in the circulation on mdr2 Pgp expression and activity. Male mice were fed a purified diet to which either 0.1% (w/w) cholate or 0.5% (w/w) ursodeoxycholate was added. This led to a near-complete replacement of the endogenous bile salt pool (mainly tauromuricholate) by taurocholate or tauroursodeoxycholate respectively. The phospholipid secretion capacity was then determined by infusion of increasing amounts of tauroursodeoxycholate. Cholate feeding resulted in a 55% increase in maximal phospholipid secretion compared with that in mice on the control diet. Northern blotting revealed that cholate feeding increased mdr2 Pgp mRNA levels by 42%. Feeding with ursodeoxycholate did not influence the maximum rate of phospholipid output or the mdr2 mRNA content. Female mice had a higher basal mdr2 Pgp mRNA level than male mice, and this was also correlated with a higher phospholipid secretion capacity. This could be explained by the 4-fold higher basal cholate content in the bile of female compared with male mice. Our results suggest that the type of bile salts in the circulation influences the expression of the mdr2 gene.

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Preparation ofN-Isopropylacrylamide/Itaconic Acid Magnetic Nanohydrogels by Modified Starch as a Crosslinker for Anticancer Drug Carriers

International Journal of Polymeric Materials ◽

10.1080/00914037.2014.996703 ◽

2015 ◽

Vol 64 (10) ◽

pp. 541-549 ◽

Cited By ~ 32

Author(s):

Marziyeh Fathi ◽

Ali Akbar Entezami ◽

Sanam Arami ◽

Mohammad-Reza Rashidi

Keyword(s):

Anticancer Drug ◽

Itaconic Acid ◽

Drug Carriers ◽

Modified Starch

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Characteristics of bile salt uptake into skate hepatocytes

Biochemical Journal ◽

10.1042/bj2990665 ◽

1994 ◽

Vol 299 (3) ◽

pp. 665-670 ◽

Cited By ~ 14

Author(s):

G Fricker ◽

V Dubost ◽

K Finsterwald ◽

J L Boyer

Keyword(s):

Substrate Specificity ◽

Bile Salt ◽

Transport System ◽

Bile Salts ◽

Organic Anion ◽

Anion Transport ◽

Organic Anion Transport ◽

Salt Uptake ◽

Anion Transport System ◽

Alpha 7

The substrate specificity for the transporter that mediates the hepatic uptake of organic anions in freshly isolated hepatocytes of the elasmobranch little skate (Raja erinacea) was determined for bile salts and bile alcohols. The Na(+)-independent transport system exhibits a substrate specificity, which is different from the specificity of Na(+)-dependent bile salt transport in mammals. Unconjugated and conjugated di- and tri-hydroxylated bile salts inhibit uptake of cholyltaurine and cholate competitively. Inhibition is significantly greater with unconjugated as opposed to glycine- or taurine-conjugated bile salts. However, the number of hydroxyl groups in the steroid moiety of the bile salts has only minor influences on the inhibition by the unconjugated bile salts. Since the transport system seems to represent an archaic organic-anion transport system, other anions, such as dicarboxylates, amino acids and sulphate, were also tested, but had no inhibitory effect on bile salt uptake. To clarify whether bile alcohols, the physiological solutes in skate bile, share this transport system, cholyltaurine transport was studied after addition of 5 beta-cholestane-3 beta,5 alpha,6 beta-triol, 5 alpha-cholestan-3 beta-ol and 5 beta-cholestane-3 alpha, 7 alpha, 12 alpha-triol. These bile alcohols inhibit cholyltaurine uptake non-competitively. In contrast, uptake of 5 beta-cholestane-3 alpha,7 alpha,12 alpha-triol, which is Na(+)-independent, is not inhibited by cholyltaurine. The findings further characterize a Na(+)-independent organic-anion transport system in skate liver cells, which is not shared by bile alcohols and has preference for unconjugated lipophilic bile salts.

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Studies on the interactions between bile salts and food emulsifiers under in vitro duodenal digestion conditions to evaluate their bile salt binding potential

Colloids and Surfaces B Biointerfaces ◽

10.1016/j.colsurfb.2018.11.024 ◽

2019 ◽

Vol 174 ◽

pp. 493-500 ◽

Cited By ~ 8

Author(s):

Julieta N. Naso ◽

Fernando A. Bellesi ◽

Víctor M. Pizones Ruiz-Henestrosa ◽

Ana M.R. Pilosof

Keyword(s):

Bile Salt ◽

Bile Salts ◽

Binding Potential ◽

Food Emulsifiers

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Hepatic bile flow

Physiological Reviews ◽

10.1152/physrev.1984.64.4.1055 ◽

1984 ◽

Vol 64 (4) ◽

pp. 1055-1102 ◽

Cited By ~ 56

Author(s):

R. C. Strange

Keyword(s):

Bile Salt ◽

Bile Salts ◽

Basolateral Membrane ◽

Membrane Vesicles ◽

Critical Micellar Concentration ◽

Canalicular Membrane ◽

Receptor Proteins ◽

Subcellular Organelles ◽

Golgi Bodies ◽

Initial Event

The hepatocyte is a polar cell that can remove a variety of molecules from blood and excrete them into bile. This review is primarily concerned with the mechanism of transport of the principal anions--the bile salts--across the sinusoidal membrane, their passage through the cell, and excretion across the canalicular membrane. Clearly much of this process is poorly understood, but the study of the membrane stages should be facilitated by the ability to prepare purified sinusoidal and canalicular membrane vesicles. For example, the relative importance of albumin-binding sites as well as the putative bile salt receptor proteins can be better assessed. It seems likely that although the interaction of bile salts with receptor proteins is important, it is an initial event that puts the bile salt in the correct place for uptake to occur. The driving force for uptake is the Na+ gradient created across the basolateral membrane by the activity of the Na+-K+-ATPase. Within the cell, various modes of transport have been suggested. Several authors emphasize the importance of protein binding of bile salts, either because of their presumed ability to maintain the concentration of these anions in the hepatocyte below their critical micellar concentration or because of their putative role in transport. It is important to understand these aspects of the role of cytosolic proteins for several reasons. Knowledge of the true concentration of free bile salt within the cell should allow estimation of whether the electrochemical gradient is sufficient for bile salts to accumulate in bile without the need for active transport of molecules from the cell into the canaliculus. The compartmental model described by Strange et al. (153) offers one theoretical way of determining the concentration of free bile salt, although the problems inherent in studying amphipath binding to the membranes of subcellular organelles (31) require that the model be reevaluated by the hygroscopic-desorption method. The second role suggested for the cytosolic bile salt-binding proteins is as transport proteins. As discussed in section VI, I think it is unlikely that the proteins identified so far act in this way, and it is more likely that movement occurs by diffusion in free solution. It is also important to determine the possible involvement of subcellular organelles such as Golgi bodies. Little is known of their role in the transport of bile salts or indeed where bile salt micelles are formed.(ABSTRACT TRUNCATED AT 400 WORDS)

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Effect of intestinal resection on bile salt absorption in dogs

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1965.208.2.363 ◽

1965 ◽

Vol 208 (2) ◽

pp. 363-369 ◽

Cited By ~ 40

Author(s):

M. R. Playoust ◽

Leon Lack ◽

I. M. Weiner

Keyword(s):

Bile Salt ◽

Bile Salts ◽

Enterohepatic Circulation ◽

Sodium Taurocholate ◽

Intestinal Resection ◽

High Fat ◽

Salt Absorption ◽

Complete Failure ◽

Fat Meal

The efficiency of intestinal absorption of bile salts was evaluated by studying the rate of disappearance of radioactivity from the bile of dogs after the intravenous administration of sodium taurocholate-24-C14. Bile was sampled through an indwelling tube in the gall bladder. One day after a high-fat meal normal dogs retained 48% of the radioactivity; dogs with resection of the jejunum retained 48%, whereas those with resection of the ileum retained only 3% in the bile. This is consistent with previous observations that the ileum is the site of bile salt absorption in vitro and in anesthetized animals. Animals with resection of the ileum exhibited significant steatorrhea; however, three-fourths of the ingested fat was absorbed in spite of almost complete failure to absorb bile salts. This indicates that fat and bile salts are not normally absorbed together. Elimination of enterohepatic circulation of bile salts by resection of the ileum contributes to the observed steatorrhea.

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