Polycationic lipophilic-core dendrons as penetration enhancers for the oral administration of low molecular weight heparin

Hayes, Peter C.; Ross, Benjamin P.; Thomas, Bradley G.; Tóth, István

doi:10.1016/j.bmc.2005.08.004

Cited by 37 publications

(21 citation statements)

References 48 publications

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“…10d) showed increased permeability across Caco-2 cell monolayers and anti-arthritis activity in rats as compared to that of the native CP [59,60]. The AUC and C max of low molecular weight heparin were improved following co-administration of polylysine-(LAA 10 ) 2 per oral [63]. Of note, the enantiomeric diversity of LAAs should be considered in LAA lipidation [30,69,70,143].…”

Section: Lipoamino Acids (Laas)mentioning

confidence: 90%

Converting Peptides into Drug Leads by Lipidation

Zhang¹,

Bułaj²

2012

CMC

172

139

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Ulceration in the gastrointestinal (GI) mucosa is a common disorder in humans. It has been shown that cigarette smoking is closely related to the increase of peptic ulcer and also plays an inhibitory role on ulcer healing. However, the underlying mechanisms by which cigarette smoke exerts these adverse effects remain largely unknown. It is perhaps partly due to the complexity of chemical compositions in the smoke and furthermore their pathological actions are largely undefined. In this review, we have highlighted the potential adverse effects of the toxic chemical components in cigarette smoke and summarized their possible mechanisms of actions on ulcer formation and healing in the GI tract. We also discuss in detail how cigarette smoke disturbs cell proliferation, influences mucus synthesis and secretion, delays blood vessel formation, and interferes the innate immune responses during ulceration and repair in the GI mucosa.

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Section: Lipoamino Acids (Laas)mentioning

confidence: 90%

Converting Peptides into Drug Leads by Lipidation

Zhang¹,

Bułaj²

2012

CMC

172

139

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“…The advantage of this method is that cationic molecules such as polycationic-lipophilic-core dendrons [13], chitosan derivatives [14,15] or deoxycholylethylamine (DCEA) [16] efficiently interacted with heparin without changing its chemical structure, thus avoiding the risk of reducing heparin's anticoagulant activity [16,17]. As an illustration of this strategy, Lee et al synthesized a cationic bile acid derivative to associate with LMWH through the formation of ion pairs [16].…”

Section: Introductionmentioning

confidence: 99%

Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation

Ralay-Ranaivo

Desmaële

Bianchini

et al. 2014

Journal of Controlled Release

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Fondaparinux (Fpx) is the anticoagulant of choice in the treatment of short- and medium-term thromboembolic disease. To overcome the low oral bioavailability of Fpx, a new nanoparticulate carrier has been developed. The nanoparticles (NPs) contain squalenyl derivatives, known for their excellent oral bioavailability. They spontaneously self-assemble upon both electrostatic and hydrophobic interactions between the polyanionic Fpx and cationic squalenyl (CSq) derivatives. The preparation conditions were optimized to obtain monodisperse, stable NPs with a mean diameter in the range of 150–200 nm. The encapsulation efficiencies were around 80%. Fpx loadings reached 39 wt.%. According to structural and morphological analysis, Fpx and CSq organized in spherical multilamellar (“onion-type”) nanoparticles. Furthermore, in vivo studies in rats suggested that Fpx was well absorbed from the orally administered NPs, which totally dissociated when reaching the blood stream, leading to the release of free Fpx. The Fpx:CSq NPs improved the plasmatic concentration of Fpx in a dose-dependent manner. However, the oral bioavailability of these new NPs remained low (around 0.3%) but of note, the Cmax obtained after oral administration of 50 mg/kg NPs was close to the prophylactic plasma concentration needed to treat venous thromboembolism. Moreover, the oral bioavailability of Fpx could be dramatically increased up to 9% by including the nanoparticles into gastroresistant capsules. This study opens up new perspectives for the oral administration of Fpx and paves the way towards elaborating squalene-based NPs which self assemble without the need of covalently grafting the drug to Sq.

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“…Hayes et al [72] used polycationic, lipophilic core, carbohydrate-based, or peptide dendrons containing 4 arginine or lysine terminal residues as penetration enhancers for the oral delivery of LMWH. The dendrons act as penetration enhancers by forming lipophilic ion-pairs with the polyanionic LMWH.…”

Section: Enhancing Permeability By Formulation With Absorption Enhancersmentioning

confidence: 99%

Strategies for oral delivery of macromolecule drugs

Park

Kim

Al-Hilal

et al. 2010

Biotechnol Bioproc E

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Advances in biotechnology, gene manipulation, and protein engineering for macromolecule drugs, such as insulin, parathyroid hormone (PTH), calcitonin, human growth hormone, erythropoietin (EPO), and peptide YY (PYY) allow commercial production in large scale for diverse therapeutic uses. Other macromolecules, such as mucopolysaccharide heparin, have expanded markets through improvements in their pharmacokinetic and pharmacological effects. However, most products are available only as injectable forms and are limited to patients with no alternative therapeutic choices. Orally available macromolecule formulations are still unmet needs for improving patient compliance and expanding administration paradigms and indications. Oral delivery technologies including carrier systems, absorption enhancers, protease inhibitors, and modification by conjugating transporter or receptor recognition molecules have been developed and some are undergoing clinical studies. In this review, we discuss major obstacles for oral absorption of macromolecule drugs and summarize recent strategies to overcome the huddles related to enhancing intestinal permeation. © KSBB hÉóïçêÇëW=çê~ä=ÇÉäáîÉêóI=ã~ÅêçãçäÉÅìäÉ=ÇêìÖëI=çê~ä=~ÄëçêéíáçåI=éÉêãÉ~ÄáäáíóI=ÉåÜ~åÅÉê= = = = =

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Polycationic lipophilic-core dendrons as penetration enhancers for the oral administration of low molecular weight heparin

Cited by 37 publications

References 48 publications

Converting Peptides into Drug Leads by Lipidation

Converting Peptides into Drug Leads by Lipidation

Novel self assembling nanoparticles for the oral administration of fondaparinux: Synthesis, characterization and in vivo evaluation

Strategies for oral delivery of macromolecule drugs

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