Oral delivery of taurocholic acid linked heparin–docetaxel conjugates for cancer therapy

Khatun, Zehedina; Nurunnabi, Md; Reeck, Gerald R.; Cho, Kwang Jae; Lee, Yong-Kyu

doi:10.1016/j.jconrel.2013.04.024

Cited by 76 publications

(51 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such bile acid is taurocholic acid (TCA), which is naturally produced in humans. It has been shown that TCA enhances the absorption of heparin-docetaxel conjugates in the lower GIT, and thus, improves their efficacy (Lee et al, 2009;Khatun et al, 2013). Therefore, this study aimed to design and examine G-TCA microcapsules that target the lower GIT and measure its hypoglycemic effect on a rat model of TID.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

et al. 2015

View full text Add to dashboard Cite

Context: Gliclazide (G) is a commonly prescribed drug for Type 2 diabetes (T2D). In a recent study, we found that when G was combined with a primary bile acid, and gavaged to an animal model of Type 1 diabetes (T1D), it exerted a hypoglycemic effect. We hypothesized this to be due to metabolic activation of the primary bile acid into a secondary or a tertiary bile acid, which enhanced G solubility and absorption. The tertiary bile acid, taurocholic acid (TCA), has shown strong permeation-enhancing effects in vivo. Thus, we aimed to design, characterize, and test microcapsules incorporating G and TCA in an animal model of T1D. Methods: Microcapsules were prepared using the polymer sodium alginate (SA). G-SA microcapsules (control) and G-TCA-SA microcapsules (test) were extensively examined (in-vitro) at different pH and temperatures. The microcapsules were gavaged to diabetic rats, and blood glucose and G concentrations in serum were examined. Ex-vivo studies were also performed using a muscle cell line (C2C12), and cell viability and glucose intake post-treatment were examined. Results: G-TCA-SA microcapsules showed good stability, uniformity, and thermal and chemical excipient compatibilities. TCA did not change the size or the shape of the microcapsules, but it enhanced their mechanical resistance and reduced their swelling properties. G-TCA-SA enhanced the viability of C2C12 cells over 24 hours, and exerted a hypoglycemic effect in alloxan-induced type-1 diabetic rats. Conclusions: The incorporation of TCA into G-microcapsules resulted in functionally improved microcapsules with a positive effect on cell viability and glycemic control in Type-1 diabetic animals.

show abstract

Section: Introductionmentioning

confidence: 99%

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Khatun et al 70 demonstrated that when an absorption enhancer, tauricholic acid, was covalently attached to a Hep-DTX conjugate, the oral absorption of the conjugate was significantly enhanced (Fig 6F). The authors used diethyl amine as the linker to incorporate DTX and a high drug loading of 25-30 wt% was reported.…”

Section: Heparinmentioning

confidence: 97%

Recent progress in the development of polysaccharide conjugates of docetaxel and paclitaxel

Roy

Bhattacharyya

Ernsting

et al. 2014

WIREs Nanomed Nanobiotechnol

View full text Add to dashboard Cite

Taxanes are one of the most potent and broadest spectrum chemotherapeutics used clinically, but also induce significant side effects. Different strategies have been developed to produce a safer taxane formulation. Development of polysaccharide drug conjugates has increased in the recent years due to the demonstrated biocompatibility, biodegradability, safety and low cost of the biopolymers. This review focuses on polysaccharide taxane conjugates and provides an overview on various conjugation strategies and their effect on the efficacy. Detailed analyses on the designing factors of an effective polysaccharide drug conjugate are provided with a discussion on the future direction of this field.

show abstract

“…Aminoacids have been used as spacers for the conjugation of HA with PTX, where HA tetrabutylammonium salt was conjugated with 2'--aminoacyl--PTX using EDC/NHS activation [94]. Similar approaches consisting of previous amination of PTX or (docetaxel) DCT for subsequent reaction with the carboxylic acids of heparin in the presence of EDC/NHS were exploited to obtain heparin--PTX [95] and heparin--DCT conjugates [96], respectively. Curcumin and DOX have also been conjugated to HA, either by direct conjugation via DDC/N,N--dimethyl amino pyridine (DMAP)--mediated esterification [97], or by linker--mediated coupling using spacers such as adipic dihydrazide [98,99].…”

Section: Figurementioning

confidence: 99%

“…Due to the liability of the hydrazone bonds, exhibited pH sensitivity, with greater DOX release rates at acidic pH. The in vitro and in vivo assays showed considerable anti--tumour activity by anti--angiogenic and apoptotic effects against 4T1 breast cancer cells and in 4T1 tumour bearing--mice.As oral drug delivery is the most convenient route of administration for the patients, some authors have focused on improving the oral absorption and targeting of chemotherapeutics.Khatun et al[96] designed a strategy based on the conjugation of taurocholic acid (TCA), capable of interacting with the bile acid transporter of the small intestine, with heparin as a therapeutic polymer, and further modification of this conjugate by chemical linkage of DCT.These ternary bioconjugates self--assembled in water giving rise to NP (115 --124 nm) which showed positive results in MDA--MB231 and KB tumour bearing mice, indeed enhancing oral absorption compared to bare heparin, efficiently accumulating in tumours and improving tumour growth inhibition compared to free DCT.…”

mentioning

confidence: 99%

Self-assembling polymer systems for advanced treatment of cancer and inflammation

Palao-Suay

Gómez‐Mascaraque

Aguilar

et al. 2016

Progress in Polymer Science

View full text Add to dashboard Cite

Oral delivery of taurocholic acid linked heparin–docetaxel conjugates for cancer therapy

Cited by 76 publications

References 34 publications

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

A comprehensive study of novel microcapsules incorporating gliclazide and a permeation enhancing bile acid: hypoglycemic effect in an animal model of Type-1 diabetes

Recent progress in the development of polysaccharide conjugates of docetaxel and paclitaxel

Self-assembling polymer systems for advanced treatment of cancer and inflammation

Contact Info

Product

Resources

About