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Peptides and Drug Delivery

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Peptides and Peptide-based Biomaterials and their Biomedical Applications

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1030))

Abstract

Peptides have been used as drugs to treat various health conditions, and they are also being developed as diagnostic agents. Due to their receptor selectivity, peptides have recently been utilized for drug delivery to target drug molecules to specific types of cells (i.e. cancer cells, immune cells) to lower the side effects of the drugs. In this case, the drug is conjugated to the carrier peptide for directing the drug to the target cells (e.g. cancer cells) with higher expression of a specific receptor that recognizes the carrier peptide. As a result, the drug is directed to the target diseased cells without affecting the normal cells. Peptides are also being developed for improving drug delivery through the intestinal mucosa barrier (IMB) and the blood-brain barrier (BBB). These peptides were derived from intercellular junction proteins such as occludins, claudins, and cadherins and improve drug delivery through the IMB and BBB via the paracellular pathways. It is hypothesized that the peptides modulate protein-protein interactions in the intercellular junctions of the IMB and BBB to increase the porosity of paracellular pathways of the barriers. These modulator peptides have been shown to enhance brain delivery of small molecules and medium-sized peptides as well as a large protein such as 65 kDa albumin. In the future, this method has the potential to improve oral and brain delivery of therapeutic and diagnostic peptides and proteins.

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Abbreviations

AJ:

adherens junction

ANG:

angiopep

APaseP:

aminopeptidase P

APP:

amyloid precursor protein

BBB:

blood brain barrier

BBMEC:

bovine brain microvessel endothelial cells

CAD:

cis–asconitic anhydride–DOX

C–CPE:

clostridium perfringens enterotoxin

CNS:

central nervous systems

CPP:

cell penetrating peptide

CPT:

camptothecin

DOX:

doxorubicin

DSDS:

drug self-delivery system

DSPE-PEG:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-(polyethylene glycol)

EC-1:

extracellular domain-1

ECM:

extracellular matrix

EGF:

epidermal growth factor

EGRF:

epidermal growth factor receptor

EGTA:

ethyleneglycol-bis-(β-aminoethyl ether)-N, N′-tetraacetic acid

ERK:

extracellular signal-regulated kinases

FACS:

fluorescence-activated cell sorting

FDA:

Food and Drug Administration

FITC:

fluorescein isothiocyanate

GABA:

γ-aminobutyric acid

Gd-DTPA:

gadopentetic acid

GIP:

glucose-dependent insulinotropic peptide

GLP-1:

glucagon-like peptide-1

GMB:

glioblastoma multiforme

GnRH :

gonadotrophin-releasing hormone

HEK:

human embryonic kidney cells

HIV-1:

human immunodeficiency virus 1

HPMA:

(2-hydroxypropyl) methacrylamide

ICAM-1:

intercellular adhesion molecule-1

IMB:

intestinal mucosa barrier

JAM:

junction adhesion molecules

LFA-1:

lymphocyte function-associated antigen-1

LHRH:

luteinizing hormone-releasing hormones

LRP-1:

lipoprotein-related protein 1

MDCK:

Madin-Darby Canine Kidney Epithelial Cells

MDR1:

multi drug resistance-1

MEK:

mitogen-activated protein kinase

MMAF:

monomethyl auristatin F

MMPs:

matrix metalloproteinases

MRI:

magnetic resonance imaging

NB:

nanobubbles

NLS:

nuclear localization signal

NMR:

nuclear magnetic resonance

NRP-1:

neuropilin-1

OCT:

octreotide

ODN :

octadecanol

OVCAR-3:

ovarian cancer cell-3

PAMAM-PAsp-PEG:

poly(amidoamine)-b-poly(aspartic acid)-b-poly(ethylene glycol)

pAntp:

antennapedia homeodomain protein of Drosophila

PEG:

polyethylene glycol

PET:

positron emission tomography

pHLIP:

pH low insertion peptide

PI3K:

phosphoinositide 3-kinase

PTX:

paclitaxel

RES :

reticuloendothelial system

RGD:

Arg-Gly-Asp

SA:

stearylamine

SCCHN:

squamous cell carcinoma of head and neck

SI :

secretase inhibitor

siRNA:

small interfering RNA

STTR:

somatostatin receptors

TAMRA:

tetramethylrhodamine

TAT:

trans-activating transcriptional activator

TEER:

trans-epithelial electrical resistance

TfR:

transferrin receptor

TJ:

tight junction

TPP :

triphenylphosphonium

ZO:

zonula occludin

Zot :

zonula occludens toxin

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Acknowledgements

We would like to thank the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) for funding our research with R01-NS075374 grant. M.E.G.M thanks the NIH for NIH for an IRACDA postdoctoral fellowship (5K12GM063651). We would like to thank Nancy Harmony for proofreading this manuscript.

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Authors and Affiliations

  1. Department of Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, KS, 66047, USA

    Kavisha R. Ulapane & Teruna J. Siahaan

  2. Department of Pharmaceutical Chemistry, The University of Kansas, 2095 Constant Avenue, Lawrence, KS, 66047, USA

    Brian M. Kopec, Mario E. G. Moral & Teruna J. Siahaan

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  1. Kavisha R. Ulapane
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  2. Brian M. Kopec
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Correspondence to Teruna J. Siahaan .

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Editors and Affiliations

  1. Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, New South Wales, Australia

    Anwar Sunna

  2. Biomolecular Discovery and Design, Research Centre, Macquarie University, North Ryde, New South Wales, Australia

    Andrew Care

  3. Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, New South Wales, Australia

    Peter L. Bergquist

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Ulapane, K.R., Kopec, B.M., Moral, M.E.G., Siahaan, T.J. (2017). Peptides and Drug Delivery. In: Sunna, A., Care, A., Bergquist, P. (eds) Peptides and Peptide-based Biomaterials and their Biomedical Applications. Advances in Experimental Medicine and Biology, vol 1030. Springer, Cham. https://doi.org/10.1007/978-3-319-66095-0_8

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