Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration

Lalatsa, Aikaterini; Schätzlein, Andreas; Garrett, Natalie; Moger, Julian; Briggs, M. S.; Godfrey, Lisa; Iannitelli, Antonio; Freeman, Jay Reynolds; Uchegbu, Ijeoma F.

doi:10.1016/j.jconrel.2014.10.028

Cited by 32 publications

(21 citation statements)

References 35 publications

(75 reference statements)

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“…Furthermore peptide nanofibres in which the peptide does not contain a charged amino acid have been produced from Opalmitoyl tyrosinate ester 1leucine 5enkephalin and this molecule also is active via the intravenous route, where again the peptide alone is inactive. These peptide nanofibres act as a self assembled prodrug, releasing the drug itself from its ester linkage in vivo ( (Lalatsa, Schatzlein et al 2013;Mazza, Notman et al 2013). A passive mechanism of transport for the peptide nanofibers is envisaged due to the increased lipophilicity of the peptide amphiphiles, but the mechanism of transport has not yet been fully elucidated.…”

Section: Peptide Amphiphilesmentioning

confidence: 99%

Strategies To Deliver Peptide Drugs to the Brain

Lalatsa

Schätzlein²,

Uchegbu³

2014

Mol. Pharmaceutics

140

106

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Neurological diseases such as neurodegeneration, pain, psychiatric disorders, stroke, and brain cancers would greatly benefit from the use of highly potent and specific peptide pharmaceuticals. Peptides are especially desirable because of their low inherent toxicity. The presence of the blood brain barrier (BBB), their short duration of action, and their need for parenteral administration limits their clinical use. However, over the past decade there have been significant advances in delivering peptides to the central nervous system. Angiopep peptides developed by Angiochem (Montreal, Canada), transferrin antibodies developed by ArmaGen (Santa Monica, USA), and cell penetrating peptides have all shown promise in delivering therapeutic peptides across the BBB after intravenous administration. Noninvasive methods of delivering peptides to the brain include the use of chitosan amphiphile nanoparticles for oral delivery and nose to brain strategies. The uptake of the chitosan amphiphile nanoparticles by the gastrointestinal epithelium is important for oral peptide delivery. Finally protecting peptides from plasma degradation is integral to the success of most of these peptide delivery strategies.

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Section: Peptide Amphiphilesmentioning

confidence: 99%

Strategies To Deliver Peptide Drugs to the Brain

Lalatsa

Schätzlein²,

Uchegbu³

2014

Mol. Pharmaceutics

140

106

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“…via maleimides) or via disulphide bonds intermolecularly. Furthermore, tyrosine, serine and threonine, hydroxyl groupcontaining amino acids, are also used for chemical or enzymatic modification [8,11,15]. Finally, the peptide backbone itself can confer stability via hydrogen bonds.…”

Section: Amino Acids: the Molecular Building Blocksmentioning

confidence: 99%

“…Only peptide nanofibers are at the moment undergoing preclinical research mainly in the area of delivery across the blood-brain barrier, the oral mucosa, regenerative medicine, inflammation and cancer ( Table 2) illustrated that nanofibers permeate across the blood-brain barrier in significant amounts and able to achieve central antinociception after intravenous [11,25] and oral administration [15], and there are they only studies reporting pharmacokinetic parameters for PAs self-assemblies. Nanofibers consisted of central hydrophobic core surrounded by a β-sheet of peptides.…”

Section: Preclinical Studiesmentioning

confidence: 99%

“…Peptide amphiphiles assemble into a variety of structures mediated by electrostatic interactions between charged amino acids, hydrogen binding, π-π stacking interactions and hydrophobic associations [7,8]. Hence, many PAs are currently explored as nanomaterials for various applications including regenerative medicine [9], gene [10] and drug delivery [11]. This review will focus on the parameters affecting supramolecular engineering of peptide amphiphiles as their chemical structure and forces driving the selfassembly and the applications of peptide amphiphiles in the field of drug delivery.…”

Section: Introductionmentioning

confidence: 99%

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Peptide Self-Assemblies for Drug Delivery

Leite¹,

Barbu²,

Pilkington³

et al. 2015

CTMC

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Peptide amphiphiles (PAs) are novel engineered biomaterials able to self-assemble into supramolecular systems that have shown significant promise in drug delivery across the cell membane and across challenging biological barriers showing promise in the field of brain diseases, regenerative medicine and cancer. PAs are amino-acid block co-polymers, with a peptide backbone composed usually of 8-30 amino acids, a hydrophilic block formed by polar amino acids, a hydrophobic block which usually entails either non-polar or aromatic amino acids and alkyl, acyl or aryl lipidic tails and in some cases a spacer or a conjugated targeting moiety. Finely tuning the balance between the hydrophilic and hydrophobic blocks results in a range of supramolecular structures that are usually stabilised by hydrophobic, electrostatic, β-sheet hydrogen bonds and π-π stacking interactions. In an aqueous environment, the final size, shape and interfacial curvature of the PA is a result of the complex interplay of all these interactions. Lanreotide is the first PA to be licensed for the treatment of acromegaly and neuroendocrine tumours as a hydrogel administered subcutaneously, while a number of other PAs are undergoing preclinical development. This review discusses PAs architecture fundamentals that govern their self-assembly into supramolecular systems for applications in drug delivery.

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“…Recent advances in polymer formulations using biocompatible quaternary ammonium palmitoyl glycol chitosan (GCPQ) have resulted in nanoparticles capable of encapsulating hydrophobic drugs for enhanced delivery via IV and oral dosing routes [1][2][3] . Determining the toxicity of these nanoparticles is obviously of great importance and the mechanisms by which the nanoparticles interact with the body at the cellular level must be understood in order to intelligently engineer novel nano-medicines and better understand their modes of action.…”

Section: Introductionmentioning

confidence: 99%

Detecting polymeric nanoparticles with coherent anti-stokes Raman scattering microscopy in tissues exhibiting fixative-induced autofluorescence

et al. 2015

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Recent advances in pharmaceutical nanotechnology have enabled the development of nano-particulate medicines with enhanced drug performance. Although the fate of these nano-particles can be macroscopically tracked in the body (e.g. using radio-labeling techniques), there is little information about the sub-cellular scale mechanistic processes underlying the particle-tissue interactions, or how these interactions may correlate with pharmaceutical efficacy. To rationally engineer these nano-particles and thus optimize their performance, these mechanistic interactions must be fully understood.Coherent Anti-Stokes Raman scattering (CARS) microscopy provides a label-free means for visualizing biological samples, but can suffer from a strong non-resonant background in samples that are prepared using aldehyde-based fixatives. We demonstrate how formalin fixative affects the detection of polymeric nanoparticles within kidneys following oral administration using CARS microscopy, compared with samples that were snap-frozen. These findings have implications for clinical applications of CARS for probing nanoparticle distribution in tissue biopsies.

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Chitosan amphiphile coating of peptide nanofibres reduces liver uptake and delivers the peptide to the brain on intravenous administration

Cited by 32 publications

References 35 publications

Strategies To Deliver Peptide Drugs to the Brain

Strategies To Deliver Peptide Drugs to the Brain

Peptide Self-Assemblies for Drug Delivery

Detecting polymeric nanoparticles with coherent anti-stokes Raman scattering microscopy in tissues exhibiting fixative-induced autofluorescence

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