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A Novel Nanoemulsion-based Method To Produce Ultrasmall, Water-dispersible Nanoparticles From Chitosan, Surface Modified With Cell-penetrating Peptide For Oral Delivery Of Proteins And Peptides

Ghullam Reza Barbari, F. Dorkoosh, M. Amini, M. Sharifzadeh, F. Atyabi, Saeed Balalaie, Niyousha Rafiee Tehrani, M. Rafiee Tehrani
Published 2017 · Chemistry, Medicine

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A simple and reproducible water-in-oil (W/O) nanoemulsion technique for making ultrasmall (<15 nm), monodispersed and water-dispersible nanoparticles (NPs) from chitosan (CS) is reported. The nano-sized (50 nm) water pools of the W/O nanoemulsion serve as “nano-containers and nano-reactors”. The entrapped polymer chains of CS inside these “nano-reactors” are covalently cross-linked with the chains of polyethylene glycol (PEG), leading to rigidification and formation of NPs. These NPs possess excessive swelling properties in aqueous medium and preserve integrity in all pH ranges due to chemical cross-linking with PEG. A potent and newly developed cell-penetrating peptide (CPP) is further chemically conjugated to the surface of the NPs, leading to development of a novel peptide-conjugated derivative of CS with profound tight-junction opening properties. The CPP-conjugated NPs can easily be loaded with almost all kinds of proteins, peptides and nucleotides for oral delivery applications. Feasibility of this nanoparticulate system for oral delivery of a model peptide (insulin) is investigated in Caco-2 cell line. The cell culture results for translocation of insulin across the cell monolayer are very promising (15%–19% increase), and animal studies are actively under progress and will be published separately.
This paper references
10.1016/S0378-5173(02)00267-3
Preparation, characterization and biodistribution of ultrafine chitosan nanoparticles.
Tanima Banerjee (2002)
10.1007/s00726-013-1625-7
A mild removal of Fmoc group using sodium azide
C. Chen (2013)
10.1023/A:1012106907708
N-Trimethyl Chitosan Chloride as a Potential Absorption Enhancer Across Mucosal Surfaces: In Vitro Evaluation in Intestinal Epithelial Cells (Caco-2)
Awie R Kotzé (2004)
Nanoemulsion-based method to produce ultrasmall, water-dispersible NPs
10.1039/b901729a
Ultra-small water-dispersible fluorescent chitosan nanoparticles: synthesis, characterization and specific targeting.
Padmavathy Tallury (2009)
10.1016/j.jconrel.2014.11.004
Brain delivery of insulin boosted by intranasal coadministration with cell-penetrating peptides.
N. Kamei (2015)
10.4155/TDE.15.47
Why most oral insulin formulations do not reach clinical trials.
M. Lopes (2015)
10.1016/j.ijpharm.2007.12.037
Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: ex vivo and in vivo studies.
A. Bayat (2008)
10.1021/BM0502258
Preparation and characterization of chitosan-based nanoparticles.
Magdolna Bodnár (2005)
10.1016/S0168-3659(97)00154-5
Comparison of the effect of different chitosan salts and N-trimethyl chitosan chloride on the permeability of intestinal epithelial cells (Caco-2).
A. Kotzé (1998)
10.1038/sj.bjp.0706279
Characterisation of cell‐penetrating peptide‐mediated peptide delivery
S. Jones (2005)
10.1016/J.REACTFUNCTPOLYM.2005.06.009
Adsorption of diuretic furosemide onto chitosan nanoparticles prepared with a water-in-oil nanoemulsion system
J. Zhi (2005)
10.1007/s00592-015-0784-2
Clinical review: insulin pump-associated adverse events in adults and children
P. Ross (2015)
10.1016/j.addr.2016.01.010
Oral delivery of macromolecular drugs: Where we are after almost 100years of attempts.
E. Moroz (2016)
10.2147/IJN.S86313
Probing insulin bioactivity in oral nanoparticles produced by ultrasonication-assisted emulsification/internal gelation
M. A. Lopes (2015)
10.1111/bcpt.12515
Cell-Penetrating Peptides as Carriers for Oral Delivery of Biopharmaceuticals.
M. Kristensen (2016)
10.1007/s002280050618
Comparative pharmacokinetics and pharmacodynamics of the novel rapid-acting insulin analogue, insulin aspart, in healthy volunteers
P. Home (1999)
10.1016/j.ejpb.2013.09.014
One-month subchronic toxicity study of cell-penetrating peptides for insulin nasal delivery in rats.
E. Khafagy (2013)
10.1166/JBN.2015.1904
Simultaneous Effect of Thiolation and Carboxylation of Chitosan Particles Towards Mucoadhesive Oral Insulin Delivery Applications: An In Vitro and In Vivo Evaluation.
M. Rekha (2015)
10.1002/jps.23708
Mechanistic study of the uptake/permeation of cell-penetrating peptides across a caco-2 monolayer and their stimulatory effect on epithelial insulin transport.
N. Kamei (2013)
Acylated insulin analogs. Google Patents
J C Baker (1999)
10.1016/J.ADDR.2004.10.010
Cell-penetrating peptides: mechanism and kinetics of cargo delivery.
M. Zorko (2005)
10.1016/J.ADDR.2007.08.019
Current challenges in non-invasive insulin delivery systems: a comparative review.
E. Khafagy (2007)
10.1007/s11095-006-9122-2
Transport of Poly(Amidoamine) Dendrimers across Caco-2 Cell Monolayers: Influence of Size, Charge and Fluorescent Labeling
Kelly M. Kitchens (2006)
10.1016/S0378-5173(01)00708-6
Bioadhesive starch microspheres and absorption enhancing agents act synergistically to enhance the nasal absorption of polypeptides.
L. Illum (2001)
10.1021/mp800174g
Conjugation with cationic cell-penetrating peptide increases pulmonary absorption of insulin.
Leena N. Patel (2009)
10.1007/s11705-013-1306-9
Overcoming oral insulin delivery barriers: application of cell penetrating peptide and silica-based nanoporous composites
Huining He (2013)
10.1016/J.PROGPOLYMSCI.2009.04.001
Chitin and chitosan polymers: Chemistry, solubility and fiber formation
C. K. S. Pillai (2009)
10.1016/S0168-3659(99)00131-5
Effect of degree of quaternization of N-trimethyl chitosan chloride for enhanced transport of hydrophilic compounds across intestinal caco-2 cell monolayers.
M. Thanou (2000)
10.1166/JNN.2007.041
Chitosan-TPP nanoparticle as a release system of antisense oligonucleotide in the oral environment.
T. H. Dũng (2007)
For personal use only
10.1016/j.biomaterials.2010.05.042
Biodistribution, pharmacodynamics and pharmacokinetics of insulin analogues in a rat model: Oral delivery using pH-responsive nanoparticles vs. subcutaneous injection.
K. Sonaje (2010)
10.1016/j.xphs.2015.11.010
Applicability and Limitations of Cell-Penetrating Peptides in Noncovalent Mucosal Drug or Carrier Delivery Systems.
N. Kamei (2016)
Acylated insulin analogs
Клейтон Бейкер Джеффри (1995)
10.1016/J.CARBPOL.2005.09.023
Water-solubility of chitosan and its antimicrobial activity
Caiqin Qin (2006)
10.1002/jps.21874
Poly(epsilon-caprolactone)/eudragit nanoparticles for oral delivery of aspart-insulin in the treatment of diabetes.
C. Damgé (2010)
10.1016/j.addr.2016.02.004
Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials.
T. A. Aguirre (2016)
10.4155/tde.14.82
How to overcome the limitations of current insulin administration with new non-invasive delivery systems.
Flávia Sousa (2015)
10.1007/s00018-005-5109-0
Cell-penetrating peptides: tools for intracellular delivery of therapeutics
S. Deshayes (2005)
10.1039/C5RA17729D
Chitosan-graft-PAMAM–alginate core–shell nanoparticles: a safe and promising oral insulin carrier in an animal model
Piyasi Mukhopadhyay (2015)
10.1016/J.JCONREL.2006.12.003
A novel vitamin B12-nanosphere conjugate carrier system for peroral delivery of insulin.
K. Chalasani (2007)



This paper is referenced by
10.2147/IJN.S251627
Overcoming Multiple Absorption Barrier for Insulin Oral Delivery Using Multifunctional Nanoparticles Based on Chitosan Derivatives and Hyaluronic Acid
Zuxian Chen (2020)
10.1016/j.vaccine.2019.02.005
Induction of Th2-related immune responses and production of systemic IgA in mice intranasally immunized with Brucella abortus malate dehydrogenase loaded chitosan nanoparticles.
Sang Hee Soh (2019)
10.2147/IJN.S225086
Impact Of Penetratin Stereochemistry On The Oral Bioavailability Of Insulin-Loaded Solid Lipid Nanoparticles
Bader B. Alsulays (2019)
10.1016/j.apsb.2020.08.016
Can nanoparticles and nano‒protein interactions bring a bright future for insulin delivery?
T. Zhang (2020)
10.1080/03639045.2020.1788061
Development of orally administered insulin-loaded polymeric-oligonucleotide nanoparticles: statistical optimization and physicochemical characterization
Chun Y Wong (2020)
10.2147/IJN.S161240
Synthesis and characterization of a novel peptide-grafted Cs and evaluation of its nanoparticles for the oral delivery of insulin, in vitro, and in vivo study
Ghullam Reza Barbari (2018)
10.3390/ani11020440
Efficiency of GnRH–Loaded Chitosan Nanoparticles for Inducing LH Secretion and Fertile Ovulations in Protocols for Artificial Insemination in Rabbit Does
Eman M Hassanein (2021)
10.2174/1389203721666200210103841
The Brief Analysis of Peptide-combined Nanoparticle: Nanomedicine's Unique Value.
Jiemin Wang (2020)
10.1016/j.ijbiomac.2018.08.152
Recent advances of polysaccharide-based nanoparticles for oral insulin delivery.
Qiaobin Hu (2018)
10.3390/polym12112499
Progress in the Development of Chitosan Based Insulin Delivery Systems: A Systematic Literature Review
Francivandi Coelho Barbosa (2020)
10.35333/jrp.2019.38
Characterization and optimization of colon targeted S-adenosyl-L-methionine loaded chitosan nanoparticles
A. Ergin (2019)
10.1080/1061186X.2017.1400552
The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation
Chun Y Wong (2018)
10.25082/JPBR.2019.02.005
Developments in encapsulation of insulin: Is oral delivery now possible?
A. Singh (2019)
10.1016/j.apsb.2019.01.004
Multifunctional oral delivery systems for enhanced bioavailability of therapeutic peptides/proteins
Ying Han (2019)
10.1016/j.ijpharm.2018.12.053
Enhancement of oral bioavailability of salmon calcitonin through chitosan‐modified, dual drug‐loaded nanoparticles
L. Liu (2019)
10.1080/1061186X.2018.1486406
Advance in oral delivery systems for therapeutic protein
S. He (2019)
10.1039/C7RA07555C
Glucuronoxylan-mediated silver nanoparticles: green synthesis, antimicrobial and wound healing applications
G. Muhammad (2017)
10.1007/978-3-030-34544-0_19
Nanomaterials Used for Delivery of Bioactives
A. Jain (2020)
10.1208/s12249-018-1242-6
5β-Cholanic Acid/Glycol Chitosan Self-Assembled Nanoparticles (5β-CHA/GC-NPs) for Enhancing the Absorption of FDs and Insulin by Rat Intestinal Membranes
Chengyun Yan (2018)
10.1007/978-981-13-8747-0_4
Protein Delivery and Mimicry
Ü. Langel (2019)
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