Design and strategies for bile acid mediated therapy and imaging

Nurunnabi, Md; Khatun, Zehedina; Revuri, Vishnu; Nafiujjaman,; Cha, Seung-Bin; Cho, Sungpil; Huh, Kang Moo; Lee, Yong-Kyu

doi:10.1039/c6ra10978k

Cited by 55 publications

(47 citation statements)

References 137 publications

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“…The excipients used as carriers for drug delivery should meet the requirements of biocompatibility and biodegradability, as well as enabling adequate drug loading and controlled drug release. Bile acids are biomolecules that have received considerable interest in drug delivery research due to their biological compatibility and favorable toxicity profiles ( Nurunnabi et al, 2016 ). The advantage of bile acids as drug absorption enhancers is their ability to act as both drug solubilizing and permeation-modifying agents.…”

Section: Introductionmentioning

confidence: 99%

“…Besides, the most of absorption enhancers use the paracellular pathways or the rupture of tight junctions to deliver the drug molecules, which is often insufficient in comparison to transporter-mediated active transport. As bile acids are efficiently absorbed via the apical sodium-dependent bile acid transporter (ASBT) in the ileum, this protein may also serve as a target for improving oral bioavailability of poorly absorbed drugs that are chemically conjugated or physically complexed with bile acids ( Nurunnabi et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

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Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

et al. 2018

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Bile acids have received considerable interest in the drug delivery research due to their peculiar physicochemical properties and biocompatibility. The main advantage of bile acids as drug absorption enhancers is their ability to act as both drug solubilizing and permeation-modifying agents. Therefore, bile acids may improve bioavailability of drugs whose absorption-limiting factors include either poor aqueous solubility or low membrane permeability. Besides, bile acids may withstand the gastrointestinal impediments and aid in the transporter-mediated absorption of physically complexed or chemically conjugated drug molecules. These biomolecules may increase the drug bioavailability also at submicellar levels by increasing the solubility and dissolution rate of non-polar drugs or through the partition into the membrane and increase of membrane fluidity and permeability. Most bile acid-induced effects are mediated by the nuclear receptors that activate transcriptional networks, which then affect the expression of a number of target genes, including those for membrane transport proteins, affecting the bioavailability of a number of drugs. Besides micellar solubilization, there are many other types of interactions between bile acids and drug molecules, which can influence the drug transport across the biological membranes. Most common drug-bile salt interaction is ion-pairing and the formed complexes may have either higher or lower polarity compared to the drug molecule itself. Furthermore, the hydroxyl and carboxyl groups of bile acids can be utilized for the covalent conjugation of drugs, which changes their physicochemical and pharmacokinetic properties. Bile acids can be utilized in the formulation of conventional dosage forms, but also of novel micellar, vesicular and polymer-based therapeutic systems. The availability of bile acids, along with their simple derivatization procedures, turn them into attractive building blocks for the design of novel pharmaceutical formulations and systems for the delivery of drugs, biomolecules and vaccines. Although toxic properties of hydrophobic bile acids have been described, their side effects are mostly produced when present in supraphysiological concentrations. Besides, minor structural modifications of natural bile acids may lead to the creation of bile acid derivatives with the reduced toxicity and preserved absorption-enhancing activity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

et al. 2018

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“…Bile salts may serve as effective aids in drug formulation since they may improve absorption through both transcellular and intercellular paths. An investigation has shown the enhancement of heparin absorption by either the chemical conjugation of heparin or physical mixing with bile acids [55][56][57].…”

Section: Permeation Enhancers Approach (Pes)mentioning

confidence: 99%

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

et al. 2019

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Objectives The main objective of present review is to explore and evaluate the effectiveness of recently developed methods to improve the bioavailability of orally administered biopharmaceutical drugs. Methods A systematic search of sciencedirect, tandfonline and Google Scholar databases based on various sets of keywords was performed. All results were evaluated based on their abstracts, and irrelevant studies were neglected during further evaluation. Results At present, biopharmaceuticals are used as injectable therapies as they are not absorbed adequately from the different routes of drug administration, particularly the oral one. Their insufficient absorption is attributed to their high molecular weight, degradation by proteolytic enzymes, high hydrophilicity and rigidity of the absorptive tissues. From industrial aspect incorporation of enzyme inhibitors (EIs) and permeation enhancers (PEs) and mucoadhesive polymers into conventional dosage forms may be the easiest way of formulation of orally administered macromolecular drugs, but the effectiveness of protection and absorption enhancement here is the most questionable. Conjugation may be problematic from regulatory aspect. Encapsulation into lipid-based vesicles sufficiently protects the incorporated macromolecule and improves intestinal uptake but have considerable stability issues. In contrast, polymeric nanocarriers may provide good stability but provides lower internalization efficacy in comparison with the lipid-based carriers. Conclusion It can be concluded that the combination of the advantages of mucoadhesive polymeric and lid-based carriers in hybrid lipid/polymer nanoparticles may result in improved absorption and might represent a potential means for the oral administration of therapeutic proteins in the near future.

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“…The steroidal structures of bile acids can induce hydrophobic interaction with drugs and thus enhance drug-loading efficiency. 15 Furthermore, intermolecular hydrogen bonding between hydroxyl and/or carboxyl groups may contribute a complementary mechanism to the micellization process. 16 Bile acids can form mixed micelles when combined with polar lipids, conventional surfactants, or amphiphilic drugs, usually with lower critical micelle concentration (CMC) and better solubilization capacity than the individual components, due to synergistic interactions.…”

Section: Introductionmentioning

confidence: 99%

“…Bile acids have an enhanced affinity toward hydrophobic drugs. 15 The interaction between NaC and PTX may protect PTX-CMs from degradation in blood circulation, and thus achieve better PTX delivery to tumors. Thirdly, NaC enhanced the circulation time of PTX-CMs in the bloodstream.…”

mentioning

confidence: 99%

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

Zhang¹,

Wu²,

Zhang³

et al. 2017

IJN

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Purpose Polymeric micelles are attractive nanocarriers for tumor-targeted delivery of paclitaxel (PTX). High antitumor efficacy and low toxicity require that PTX mainly accumulated in tumors with little drug exposure to normal tissues. However, many PTX-loaded micelle formulations suffer from low stability, fast drug release, and lack of tumor-targeting capability in the circulation. To overcome these challenges, we developed a micellar formulation that consists of sodium cholate (NaC) and monomethoxy poly (ethylene glycol)- block -poly ( d , l -lactide) (mPEG-PDLLA). Methods PTX-loaded NaC-mPEG-PDLLA micelles (PTX-CMs) and PTX-loaded mPEG-PDLLA micelles (PTX-Ms) were formulated, and their characteristics, particle size, surface morphology, release behavior in vitro, pharmacokinetics and in vivo biodistributions were researched. In vitro and in vivo tumor inhibition effects were systematically investigated. Furthermore, the hemolysis and acute toxicity of PTX-CMs were also evaluated. Results The size of PTX-CMs was 53.61±0.75 nm and the ζ-potential was −19.73±0.68 mV. PTX was released much slower from PTX-CMs than PTX-Ms in vitro. Compared with PTX-Ms, the cellular uptake of PTX-CMs was significantly reduced in macrophages and significantly increased in human cancer cells, and therefore, PTX-CMs showed strong growth inhibitory effects on human cancer cells. In vivo, the plasma AUC 0−t of PTX-CMs was 1.8-fold higher than that of PTX-Ms, and 5.2-fold higher than that of Taxol. The biodistribution study indicated that more PTX-CMs were accumulated in tumor than PTX-Ms and Taxol. Furthermore, the significant antitumor efficacy of PTX-CMs was observed in mice bearing BEL-7402 hepatocellular carcinoma and A549 lung carcinoma. Results from drug safety assessment studies including acute toxicity and hemolysis test revealed that the PTX-CMs were safe for in vivo applications. Conclusion These results strongly revealed that NaC-mPEG-PDLLA micelles can tumor-target delivery of PTX and enhance drug penetration in tumor, suggesting that NaC-mPEG-PDLLA micelles are promising nanocarrier systems for anticancer drugs delivery.

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Design and strategies for bile acid mediated therapy and imaging

Abstract: Bioinspired materials have received substantial attention across biomedical, biological, and drug delivery research because of their high biocompatibility and lower toxicity compared with synthetic materials.

Cited by 55 publications

References 137 publications

Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

Bile Acids and Their Derivatives as Potential Modifiers of Drug Release and Pharmacokinetic Profiles

Review of recently used techniques and materials to improve the efficiency of orally administered proteins/peptides

Sodium cholate-enhanced polymeric micelle system for tumor-targeting delivery of paclitaxel

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