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Molecules
2017 Oct 12;2210:. doi: 10.3390/molecules22101707.
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Electrostatic Self-Assembled Chitosan-Pectin Nano- and Microparticles for Insulin Delivery.
Maciel VBV
,
Yoshida CMP
,
Pereira SMSS
,
Goycoolea FM
,
Franco TT
.
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A polyelectrolyte complex system of chitosan-pectin nano- and microparticles was developed to encapsulate the hormone insulin. The aim of this work was to obtain small particles for oral insulin delivery without chemical crosslinkers based on natural and biodegradable polysaccharides. The nano- and microparticles were developed using chitosans (with different degrees of acetylation: 15.0% and 28.8%) and pectin solutions at various charge ratios (n⁺/n- given by the chitosan/pectin mass ratio) and total charge. Nano- and microparticles were characterized regarding particle size, zeta potential, production yield, encapsulation efficiency, stability in different media, transmission electron microscopy and cytotoxicity assays using Caco-2 cells. The insulin release was evaluated in vitro in simulated gastric and intestinal media. Small-sized particles (~240-~1900 nm) with a maximum production yield of ~34.0% were obtained. The highest encapsulation efficiency (~62.0%) of the system was observed at a charge ratio (n⁺/n-) 5.00. The system was stable in various media, particularly in simulated gastric fluid (pH 1.2). Transmission electron microscopy (TEM) analysis showed spherical shape particles when insulin was added to the system. In simulated intestinal fluid (pH 6.8), controlled insulin release occurred over 2 h. In vitro tests indicated that the proposed system presents potential as a drug delivery for oral administration of bioactive peptides.
Figure 1. Variation of the ζ-potential (zeta-potential) with pH for chitosan and pectin solutions prepared in 100 mM NaCl (as in legend) at 25 °C.
Figure 2. Variation of the Z-average hydrodynamic diameter and ζ-potential with charge ratio (n+/n−) of particles comprised by chitosan of different DA and pectin at pH 2.7 and 25 °C for systems with: (a) total charge 1.0 × 10−6 M, chitosan degree of acetylation (DA) 15.0%; (b) total charge 2.0 × 10−6 M, chitosan DA 15.0%; (c) total charge 1.0 × 10−6 M, chitosan DA 28.8; and (d) total charge 2.0 × 10−6 M, chitosan DA 28.8%.
Figure 3. Evolution of the ζ-average hydrodynamic diameter of insulin-loaded particles comprised by chitosans of varying DA and pectin mixed at different charge ratio (n+/n− as shown in labels) during incubation at 37 ± 1 °C for 24 h in: (a) 150 mM NaCl (pH 7.4); (b) MEM (minimal essential medium, pH 7.4); (c) SGF (simulated gastric fluid, pH 1.2) and (d) SIF (simulated intestinal fluid, pH 6.8).
Figure 4. Representative transmission electron microscopy (TEM) images of (a) blank (unloaded) particles (chitosan DA 28.8% and charge ratio (n+/n−) 0.25); (b) Blank (unloaded) particles (chitosan DA 28.8% and charge ratio (n+/n−) 5.00); (c) insulin-loaded (chitosan DA 28.8% and charge ratio (n+/n−) 0.25); and (d) insulin-loaded (chitosan DA 28.8% and charge ratio (n+/n−) 5.00).
Figure 5. Cell viability (MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay) of Caco-2 cells after treatment (4 h at 37 ± 0.1 °C) varying concentrations of nano- and microparticles at different charge ratio (n+/n−) (as in figure legends). (a) Blank (unloaded) particles, chitosan DA 15.0%; (b) Insulin-loaded, chitosan DA 15.0%; (c) Blank (unloaded) particles, chitosan DA 28.8% and (d) Insulin-loaded, chitosan DA 28.8% (values represent average and standard deviations of three biological replicates).
Figure 6. Percentage cumulative of insulin release from nano- and microparticles prepared using chitosan of different DA and pectin at charge ratio (n+/n−) 5.00 during incubation for 120 min at 37 ± 0.1 °C in: (a) Simulated gastric fluid (pH 1.2) and (b) Simulated intestinal fluid (pH 6.8).
Abodinar,
A novel method to estimate the stiffness of carbohydrate polyelectrolyte polymers based on the ionic strength dependence of zeta potential.
2014, Pubmed
Abodinar,
A novel method to estimate the stiffness of carbohydrate polyelectrolyte polymers based on the ionic strength dependence of zeta potential.
2014,
Pubmed
Alai,
Application of polymeric nanoparticles and micelles in insulin oral delivery.
2015,
Pubmed
Andreani,
Effect of mucoadhesive polymers on the in vitro performance of insulin-loaded silica nanoparticles: Interactions with mucin and biomembrane models.
2015,
Pubmed
Avadi,
Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method.
2010,
Pubmed
Bagre,
Alginate coated chitosan core shell nanoparticles for oral delivery of enoxaparin: in vitro and in vivo assessment.
2013,
Pubmed
Bayat,
Nanoparticles of quaternized chitosan derivatives as a carrier for colon delivery of insulin: ex vivo and in vivo studies.
2008,
Pubmed
Biswas,
Development and characterization of alginate coated low molecular weight chitosan nanoparticles as new carriers for oral vaccine delivery in mice.
2015,
Pubmed
Cerchiara,
Chitosan based micro- and nanoparticles for colon-targeted delivery of vancomycin prepared by alternative processing methods.
2015,
Pubmed
Chen,
Recent advances in chitosan-based nanoparticles for oral delivery of macromolecules.
2013,
Pubmed
Chronopoulou,
Chitosan based nanoparticles functionalized with peptidomimetic derivatives for oral drug delivery.
2016,
Pubmed
Coimbra,
Preparation and chemical and biological characterization of a pectin/chitosan polyelectrolyte complex scaffold for possible bone tissue engineering applications.
2011,
Pubmed
Duncan,
Dendrimer biocompatibility and toxicity.
2005,
Pubmed
Fonte,
Polymer-based nanoparticles for oral insulin delivery: Revisited approaches.
2015,
Pubmed
Fuenzalida,
Affinity protein-based FRET tools for cellular tracking of chitosan nanoparticles and determination of the polymer degree of acetylation.
2014,
Pubmed
Fàbregas,
Impact of physical parameters on particle size and reaction yield when using the ionic gelation method to obtain cationic polymeric chitosan-tripolyphosphate nanoparticles.
2013,
Pubmed
Ghaffari,
Preparation and characterization of free mixed-film of pectin/chitosan/Eudragit RS intended for sigmoidal drug delivery.
2007,
Pubmed
Goycoolea,
Chitosan-alginate blended nanoparticles as carriers for the transmucosal delivery of macromolecules.
2009,
Pubmed
Goycoolea,
Physical Properties and Stability of Soft Gelled Chitosan-Based Nanoparticles.
2016,
Pubmed
Gursoy,
Excipient effects on in vitro cytotoxicity of a novel paclitaxel self-emulsifying drug delivery system.
2003,
Pubmed
Herrero,
Polymer-based oral peptide nanomedicines.
2012,
Pubmed
Hosseininasab,
Synthesis, characterization, and in vitro studies of PLGA-PEG nanoparticles for oral insulin delivery.
2014,
Pubmed
Jardim,
Physico-chemical characterization and cytotoxicity evaluation of curcumin loaded in chitosan/chondroitin sulfate nanoparticles.
2015,
Pubmed
Khafagy,
Current challenges in non-invasive insulin delivery systems: a comparative review.
2007,
Pubmed
Kleine-Brueggeney,
A rational approach towards the design of chitosan-based nanoparticles obtained by ionotropic gelation.
2015,
Pubmed
Krauland,
Chitosan/cyclodextrin nanoparticles as macromolecular drug delivery system.
2007,
Pubmed
Kumar,
Carboxymethyl gum kondagogu-chitosan polyelectrolyte complex nanoparticles: preparation and characterization.
2013,
Pubmed
Lavertu,
A validated 1H NMR method for the determination of the degree of deacetylation of chitosan.
2003,
Pubmed
Leonard,
Evaluation of the Caco-2 monolayer as a model epithelium for iontophoretic transport.
2000,
Pubmed
Loh,
Cytotoxicity of monodispersed chitosan nanoparticles against the Caco-2 cells.
2012,
Pubmed
Lu,
Polyelectrolyte complex nanoparticles of amino poly(glycerol methacrylate)s and insulin.
2012,
Pubmed
Luo,
Solid lipid nanoparticles for oral drug delivery: chitosan coating improves stability, controlled delivery, mucoadhesion and cellular uptake.
2015,
Pubmed
Maciel,
Chitosan/pectin polyelectrolyte complex as a pH indicator.
2015,
Pubmed
,
Echinobase
Marschütz,
Oral peptide drug delivery: polymer-inhibitor conjugates protecting insulin from enzymatic degradation in vitro.
2000,
Pubmed
McConaughy,
Structural characterization and solution properties of a galacturonate polysaccharide derived from Aloe vera capable of in situ gelation.
2008,
Pubmed
Morishita,
Is the oral route possible for peptide and protein drug delivery?
2006,
Pubmed
Mukhopadhyay,
pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.
2015,
Pubmed
Mukhopadhyay,
Oral insulin delivery by self-assembled chitosan nanoparticles: in vitro and in vivo studies in diabetic animal model.
2013,
Pubmed
Ninan,
Pectin/carboxymethyl cellulose/microfibrillated cellulose composite scaffolds for tissue engineering.
2013,
Pubmed
Pan,
Bioadhesive polysaccharide in protein delivery system: chitosan nanoparticles improve the intestinal absorption of insulin in vivo.
2002,
Pubmed
Rinaudo,
Characterization of chitosan. Influence of ionic strength and degree of acetylation on chain expansion.
1993,
Pubmed
Rodriguez-Juan,
Cell surface phenotype and cytokine secretion in Caco-2 cell cultures: increased RANTES production and IL-2 transcription upon stimulation with IL-1beta.
2001,
Pubmed
Rosenbohm,
Chemically methylated and reduced pectins: preparation, characterisation by 1H NMR spectroscopy, enzymatic degradation, and gelling properties.
2003,
Pubmed
Russo,
Preparation, characterization and in vitro antiviral activity evaluation of foscarnet-chitosan nanoparticles.
2014,
Pubmed
Sadeghi,
Permeation enhancer effect of chitosan and chitosan derivatives: comparison of formulations as soluble polymers and nanoparticulate systems on insulin absorption in Caco-2 cells.
2008,
Pubmed
Soliman,
Hydrocaffeic acid-chitosan nanoparticles with enhanced stability, mucoadhesion and permeation properties.
2014,
Pubmed
Sonia,
An overview of natural polymers for oral insulin delivery.
2012,
Pubmed
Trapani,
Systemic heparin delivery by the pulmonary route using chitosan and glycol chitosan nanoparticles.
2013,
Pubmed
Ubaidulla,
Development and characterization of chitosan succinate microspheres for the improved oral bioavailability of insulin.
2007,
Pubmed
Vihola,
Cytotoxicity of thermosensitive polymers poly(N-isopropylacrylamide), poly(N-vinylcaprolactam) and amphiphilically modified poly(N-vinylcaprolactam).
2005,
Pubmed
Whiting,
IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030.
2011,
Pubmed
Wild,
Global prevalence of diabetes: estimates for the year 2000 and projections for 2030.
2004,
Pubmed
Woitiski,
Strategies toward the improved oral delivery of insulin nanoparticles via gastrointestinal uptake and translocation.
2008,
Pubmed
Zhang,
Preparation and characterization of insulin-loaded bioadhesive PLGA nanoparticles for oral administration.
2012,
Pubmed
Zhang,
Preparation of polyelectrolyte complex nanoparticles of chitosan and poly(2-acry1amido-2-methylpropanesulfonic acid) for doxorubicin release.
2016,
Pubmed
