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An Enteric-Coated Polyelectrolyte Nanocomplex Delivers Insulin In Rat Intestinal Instillations When Combined With A Permeation Enhancer

Svenja Sladek, Fiona McCartney, M. Eskander, D. Dunne, M. Santos-Martinez, F. Benetti, L. Tajber, D. Brayden
Published 2020 · Chemistry, Medicine

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The use of nanocarriers is being researched to achieve oral peptide delivery. Insulin-associated anionic polyelectrolyte nanoparticle complexes (PECs) were formed that comprised hyaluronic acid and chitosan in an optimum mass mixing ratio of 5:1 (MR 5), followed by coating with a pH-dependent polymer. Free insulin was separated from PECs by size exclusion chromatography and then measured by HPLC. The association efficiency of insulin in PECs was >95% and the loading was ~83 µg/mg particles. Dynamic light scattering and nanoparticle tracking analysis of PECs revealed low polydispersity, a negative zeta potential range of −40 to −50 mV, and a diameter range of 95–200 nm. Dissolution studies in simulated small intestinal fluid (FaSSIF-V2) revealed that the PECs were colloidally stable. PECs that were coated with Eudragit® L-100 delayed insulin release in FaSSIF-V2 and protected insulin against pancreatin attack more than uncoated PECs. Uncoated anionic PECs interacted weakly with mucin in vitro and were non-cytotoxic to Caco-2 cells. The coated and uncoated PECs, both concentrated further by ultrafiltration, permitted dosing of 50 IU/kg in rat jejunal instillations, but they failed to reduce plasma glucose or deliver insulin to the blood. When ad-mixed with the permeation enhancer (PE), sucrose laurate (100 mM), the physicochemical parameters of coated PECs were relatively unchanged, however blood glucose was reduced by 70%. In conclusion, the use of a PE allowed for the PEC-released bioactive insulin to permeate the jejunum. This has implications for the design of orally delivered particles that can release the payload when formulated with enhancers.
This paper references
10.1016/j.ijpharm.2012.07.011
Exploring the assembly process and properties of novel crosslinker-free hyaluronate-based polyelectrolyte complex nanocarriers.
A. Umerska (2012)
10.1016/j.drudis.2012.03.019
An overview of natural polymers for oral insulin delivery.
T. Sonia (2012)
10.1016/j.jconrel.2009.11.018
Efficient induction of immune responses through intradermal vaccination with N-trimethyl chitosan containing antigen formulations.
S. Bal (2010)
10.1023/B:PHAM.0000012150.60180.e3
Effect of Chitosan on Epithelial Cell Tight Junctions
J. Smith (2004)
10.1007/s11095-007-9367-4
Alginate/Chitosan Nanoparticles are Effective for Oral Insulin Delivery
B. Sarmento (2007)
10.1016/j.peptides.2018.01.002
Recent insights in the use of nanocarriers for the oral delivery of bioactive proteins and peptides
P. Batista (2018)
10.3390/polym10070701
Hyaluronic Acid in the Third Millennium
Arianna Fallacara (2018)
10.1007/BF01017860
The theory of Ostwald ripening
P. Voorhees (1985)
10.1002/mabi.200700190
Novel hyaluronan-based nanocarriers for transmucosal delivery of macromolecules.
M. de la Fuente (2008)
10.1021/BM015598X
Electrophoretic light scattering studies of chitosans with different degrees of N-acetylation.
S. Strand (2001)
10.1007/s11095-006-9209-9
Estimation of Intragastric Solubility of Drugs: In What Medium?
M. Vertzoni (2006)
10.1038/nprot.2008.75
Neutral red uptake assay for the estimation of cell viability/cytotoxicity
G. Repetto (2008)
10.1016/j.ijpharm.2014.10.023
Intermolecular interactions between salmon calcitonin, hyaluronate, and chitosan and their impact on the process of formation and properties of peptide-loaded nanoparticles.
A. Umerska (2014)
10.1016/j.jconrel.2017.02.024
Rational design of polyarginine nanocapsules intended to help peptides overcoming intestinal barriers.
Zhigao Niu (2017)
10.1016/J.EJPB.2004.10.006
Strategic approaches for overcoming peptide and protein instability within biodegradable nano- and microparticles.
U. Bilati (2005)
Self-assembled Polyelectrolyte Nanocomplexes of Alginate, Chitosan and Ovalbumin.
Mateja Cegnar (2010)
10.1016/j.ijpharm.2013.06.068
Modulation of stability and mucoadhesive properties of chitosan microspheres for therapeutic gastric application.
M. Fernandes (2013)
10.1016/j.carbpol.2015.01.066
Self-assembled carrageenan/protamine polyelectrolyte nanoplexes-Investigation of critical parameters governing their formation and characteristics.
M. Dul (2015)
10.1023/A:1018984731584
Intestinal Permeability Enhancement: Efficacy, Acute Local Toxicity, and Reversibility
E. S. Swenson (2004)
10.5812/ircmj.17(4)2015.16761
Evaluation of In Vivo Transfection Efficiency of Eudragit Coated Nanoparticles of Chitosan-DNA: A pH-sensitive System Prepared for Oral DNA Delivery
Sedigheh Momenzadeh (2015)
10.1016/j.ijpharm.2010.08.020
Tight junction modulation by chitosan nanoparticles: comparison with chitosan solution.
D. Vllasaliu (2010)
10.1016/J.COLSURFB.2006.09.012
Development and characterization of new insulin containing polysaccharide nanoparticles.
B. Sarmento (2006)
10.1002/PPSC.200601031
NanoParticle Tracking Analysis – The Halo™ System
A. Malloy (2006)
10.1016/j.ijbiomac.2011.10.016
Analysis of the interactions between Eudragit® L100 and porcine pancreatic trypsin by calorimetric techniques.
M. Braia (2012)
10.1016/j.ejpb.2015.04.006
Chondroitin-based nanoplexes as peptide delivery systems--Investigations into the self-assembly process, solid-state and extended release characteristics.
A. Umerska (2015)
10.1016/j.jconrel.2018.07.045
Physicochemical, pharmacokinetic and pharmacodynamic analyses of amphiphilic cyclodextrin‐based nanoparticles designed to enhance intestinal delivery of insulin
E. Presas (2018)
10.1016/S0927-7765(99)00157-5
The role of PEG on the stability in digestive fluids and in vivo fate of PEG-PLA nanoparticles following oral administration.
Tobío (2000)
10.1111/jphp.12912
The pig as a preclinical model for predicting oral bioavailability and in vivo performance of pharmaceutical oral dosage forms: a PEARRL review
Laura J Henze (2019)
10.1021/BM049786+
Versatile and efficient formation of colloids of biopolymer-based polyelectrolyte complexes.
C. Schatz (2004)
10.1007/S00396-004-1111-6
Electrostatic interactions between amphoteric latex particles and proteins
C. Chern (2004)
10.1016/J.EJPB.2005.09.008
Preparation and release of salbutamol from chitosan and chitosan co-spray dried compacts and multiparticulates.
D. Corrigan (2006)
10.1016/J.EJPS.2005.02.008
A comparative study of the potential of solid triglyceride nanostructures coated with chitosan or poly(ethylene glycol) as carriers for oral calcitonin delivery.
M. Garcia-Fuentes (2005)
10.1016/J.IJPHARM.2007.05.015
Peroral delivery of insulin using chitosan derivatives: a comparative study of polyelectrolyte nanocomplexes and nanoparticles.
Anchalee Jintapattanakit (2007)
10.1038/nprot.2017.052
Use of luciferase probes to measure ATP in living cells and animals
G. Morciano (2017)
10.1016/j.ijpharm.2019.118720
Bio-nanotechnological advancement of orally administered insulin nanoparticles: Comprehensive review of experimental design for physicochemical characterization.
Chun Y Wong (2019)
10.1016/j.jconrel.2011.07.014
Covalently stabilized trimethyl chitosan-hyaluronic acid nanoparticles for nasal and intradermal vaccination.
R. Verheul (2011)
10.1021/ar200234q
pH-responsive nanoparticles shelled with chitosan for oral delivery of insulin: from mechanism to therapeutic applications.
H. Sung (2012)
Polyelectrolyte complexes as nanoparticulate drug delivery systems
Lidia Taber (2015)
10.1016/j.ijpharm.2009.04.014
The complexation between novel comb shaped amphiphilic polyallylamine and insulin: towards oral insulin delivery.
C. Thompson (2009)
Intracellular trafficking of hyaluronic acid-chitosan oligomer-based nanoparticles in cultured human ocular surface cells
Laura Contreras-Ruiz (2011)
10.1021/MA00230A037
Polyelectrolyte properties of sodium hyaluronate. 2. Potentiometric titration of hyaluronic acid
R. Cleland (1982)
10.1007/s11095-014-1449-5
Tetanus Toxoids Loaded Glucomannosylated Chitosan Based Nanohoming Vaccine Adjuvant with Improved Oral Stability and Immunostimulatory Response
H. Harde (2014)
10.1016/j.jconrel.2014.06.022
In vivo proof of concept of oral insulin delivery based on a co-administration strategy with the cell-penetrating peptide penetratin.
E. J. B. Nielsen (2014)
10.1016/j.ijbiomac.2017.05.138
Can natural polymers assist in delivering insulin orally?
M. Nur (2017)
10.3727/095535491820873191
Use of an aqueous soluble tetrazolium/formazan assay for cell growth assays in culture.
A. Cory (1991)
10.1016/j.biomaterials.2010.01.042
Enteric-coated capsules filled with freeze-dried chitosan/poly(gamma-glutamic acid) nanoparticles for oral insulin delivery.
K. Sonaje (2010)
10.2174/1573412911309030010
Factorial Approach for the Development of Stability Indicating HPLC Assay of Recombinant Human Insul
Rajendra Narayan Dash (2013)
10.1007/s11095-007-9459-1
Multifunctional Nanoparticulate Polyelectrolyte Complexes
Sean M. Hartig (2007)
10.1002/mabi.201300515
Thiolated eudragit-based nanoparticles for oral insulin delivery: preparation, characterization, and evaluation using intestinal epithelial cells in vitro.
Y. Zhang (2014)
10.1016/j.cmpb.2010.01.007
PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel
Y. Zhang (2010)
10.1021/JA037470O
Control of protein structure and function through surface recognition by tailored nanoparticle scaffolds.
Rui Hong (2004)
10.1016/j.jconrel.2013.01.027
An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.
S. Ryan (2013)
10.1016/J.IJPHARM.2006.08.013
Formulation and characterization of amphotericin B-chitosan-dextran sulfate nanoparticles.
W. Tiyaboonchai (2007)
10.1016/j.jconrel.2016.04.012
Dual chitosan/albumin-coated alginate/dextran sulfate nanoparticles for enhanced oral delivery of insulin.
M. Lopes (2016)
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license
10.3390/pharmaceutics11110565
Evaluation of Sucrose Laurate as an Intestinal Permeation Enhancer for Macromolecules: Ex Vivo and In Vivo Studies
Fiona McCartney (2019)
10.1016/S0144-8617(96)00047-1
Effects of chain flexibility of chitosan molecules on the preparation, physical, and release characteristics of the prepared capsule
R. H. Chen (1996)
Use of Permeation Enhancers and Nanotechnology to Increase Intestinal Peptide Permeability
F. McCartney (2016)
10.1016/j.addr.2011.12.009
Oral drug delivery with polymeric nanoparticles: the gastrointestinal mucus barriers.
Laura M Ensign (2012)
10.1007/s11095-008-9569-4
Dissolution Media Simulating Conditions in the Proximal Human Gastrointestinal Tract: An Update
E. Jantratid (2008)
10.1016/J.JCIS.2006.07.031
Colloidal stability of pluronic F68-coated PLGA nanoparticles: a variety of stabilisation mechanisms.
M. J. Santander-Ortega (2006)
10.3390/ma11050724
The Role of Mucin in the Toxicological Impact of Polystyrene Nanoparticles
I. Inkielewicz-Stępniak (2018)
10.1016/J.EJPS.2004.03.015
Development and in vivo evaluation of an oral insulin-PEG delivery system.
P. Calceti (2004)
10.1016/J.COCIS.2010.12.005
Fate of polymeric nanocarriers for oral drug delivery
L. Plapied (2011)
10.1016/j.ijbiomac.2018.08.152
Recent advances of polysaccharide-based nanoparticles for oral insulin delivery.
Qiaobin Hu (2018)
10.1167/iovs.07-1077
Novel hyaluronic acid-chitosan nanoparticles for ocular gene therapy.
M. de la Fuente (2008)
10.1007/s13346-018-0557-x
Intra-articular delivery of a nanocomplex comprising salmon calcitonin, hyaluronic acid, and chitosan using an equine model of joint inflammation
Svenja Sladek (2018)
10.1021/BM0604754
Development of improved nanoparticulate polyelectrolyte complex physicochemistry by nonstoichiometric mixing of polyions with similar molecular weights.
Sean M. Hartig (2007)
Polyelectrolyte complexes
A F Thünemann (2004)
10.1021/bm301207a
Stability of chitosan nanoparticles cross-linked with tripolyphosphate.
Helene Jonassen (2012)
10.1021/bm801513e
Polysaccharide-based polyelectrolyte complex nanoparticles from chitosan, heparin, and hyaluronan.
Soheil Boddohi (2009)
10.1166/JBN.2014.1878
Self-assembled hyaluronate/protamine polyelectrolyte nanoplexes: synthesis, stability, biocompatibility and potential use as peptide carriers.
A. Umerska (2014)
10.1517/17425241003602259
Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems
Y. Fu (2010)
10.1517/17425247.2016.1107543
Oral insulin delivery systems using chitosan-based formulation: a review
Khalid Al Rubeaan (2016)
10.1016/j.ejpb.2008.04.008
Comparative evaluation of interpolyelectrolyte complexes of chitosan with Eudragit L100 and Eudragit L100-55 as potential carriers for oral controlled drug delivery.
R. I. Moustafine (2008)
10.1016/j.ejpb.2016.11.037
In vivo biodistribution of antihyperglycemic biopolymer‐based nanoparticles for the treatment of type 1 and type 2 diabetes
M. Lopes (2017)
10.1016/j.ejpb.2016.11.005
Polyelectrolyte complexes as prospective carriers for the oral delivery of protein therapeutics
V. Bourganis (2017)
10.1208/s12249-012-9807-2
Insulin-Loaded pH-Sensitive Hyaluronic Acid Nanoparticles Enhance Transcellular Delivery
Lina Han (2012)
Polyelectrolyte properties of sodium hyaluronate
R. L. Cleland (1982)
10.1016/j.jconrel.2017.09.003
Potential of insulin nanoparticle formulations for oral delivery and diabetes treatment
Chun Y Wong (2017)
10.3109/02652048.2015.1017619
Microencapsulation of insulin using a W/O/W double emulsion followed by complex coacervation to provide protection in the gastrointestinal tract
F. Cárdenas-Bailón (2015)
10.1016/j.biomaterials.2009.06.055
Drug permeability and mucoadhesion properties of thiolated trimethyl chitosan nanoparticles in oral insulin delivery.
Lichen Yin (2009)
10.1038/nprot.2007.303
Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers
I. Hubatsch (2007)



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