Most of the studies concerning gellan have been focused on its application as a food ingredient, however, gellan is often considered as a candidate for the development of novel pharmaceutical formulations. Taking into account that gellan is ion-sensitive, it can be assumed that its initial mechanical properties can change upon contact with body secretions. Therefore, the aim of the work was to investigate the rheological properties of pure high-acyl gellan gum hydrogel (0.4%) and its mixtures with selected simulated body fluids.
Methods
The rheological investigations were performed on rotational rheometer and included oscillatory temperature, amplitude, and frequency sweeping. The results enabled estimation of the linear viscoelastic regime, calculation of the cross-over points, and percentage of structure recovery.
Results
In the case of pure hydrogel no evidence of thermosensitivity was observed in the range of 20–40°C. In pH = 1.2 (NaCl/HCl) the hydrogel structure was almost entirely destroyed. Mixing with phosphate buffer (pH = 4.5) resulted in higher gel strength than after dilution with deionized water. The opposite effect was observed in the case of pH = 7.4. The studies performed for the mixture of GG hydrogel and mucin indicated interaction between the components. The hydrogel elasticity increased in the presence of simulated tear, but decreased in simulated saliva and vaginal fluid.
Conclusions
In this study, it was shown that the stability of a three-dimensional gellan structure may be affected by pH and the presence of mucin which most probably competed with gellan gum in divalent cations binding. The observations presented in this study may be important in terms of potential application of gellan gum as a potential carrier in drug delivery systems.
KangKSVeederGTMirrasoulPJet al.
Agar-like polysaccharide produced by a pseudomonas species: production and basic properties. Appl Environ Microb1982;
43: 1086–1091.
4.
GrasdalenH andSmidsrødO.Gelation of gellan gum. Carbohyd Polym1987;
7: 371–393.
5.
JanssonBHägerströmHFransénNet al.
The influence of gellan gum on the transfer of fluorescein dextran across rat nasal epithelium in vivo. Eur J Pharm Biopharm2005;
59: 557–564.
6.
ChandrasekaranRRadhaA andThailambalVG.Roles of potassium ions, acetyl and L-glyceryl groups in native gellan double helix: an X-ray study. Carbohyd Res1992;
224: 1–17.
7.
KasapisSGiannouliPHemberMVNet al.
Structural aspects and phase behaviour in deacylated and high acyl gellan systems. Carbohyd Polym1999;
38: 145–154.
8.
OsmałekTFroelichA andTasarekS.Application of gellan gum in pharmacy and medicine. Int J Pharm2014;
466: 328–340.
9.
MaoRTangJ andSwansonBG.Texture properties of gellan gels as affected by temperature. J Texture Stud1999;
30: 409–433.
10.
TangJTungMA andZengY.Gelling properties of gellan solutions containing monovalent and divalent cations. J Food Sci1997;
62: 688–612.
MorrisERNishinariK andRinaudoM.Gelation of gellan – a review. Food Hydrocolloid2012;
28: 373–311.
13.
MorrisERGothardMGEHemberMWNet al.
Conformational and rheological transitions of welan, rhamsan and acylated gellan. Carbohyd Polym1996;
30: 165–175.
14.
GongYWangCLaiRCet al.
An improved injectable polysaccharide hydrogel: modified gellan gum for long-term cartilage regeneration in vitro. J Mater Chem2009;
19: 1968.
15.
SutherlandIW.Novel and established applications of microbial polysaccharides. Trends Biotechnol1998;
16: 41–46.
16.
MazenFMilasM andRinaudoM.Conformational transition of native and modified gellan. Int J Biol Macromol1999;
26: 109–118.
17.
Flores-HuicocheaERodríguez-HernándezAIEspinosa-SolaresTet al.
Sol-gel transition temperatures of high acyl gellan with monovalent and divalent cations from rheological measurements. Food Hydrocolloid2013;
31: 299–205.
18.
PiconeCSF andCunhaRL.Influence of pH on formation and properties of gellan gels. Carbohyd Polym2011;
84: 662–668.
19.
TeratsuboMTanakaY andSaekiS.Measurement of stress and strain during tensile testing of gellan gum gels: effect of deformation speed. Carbohyd Polym2002;
47: 1–5.
20.
OgawaEMatsuzawaH andIwahashiM.Conformational transition of gellan gum of sodium, lithium, and potassium types in aqueous solutions. Food Hydrocolloid2002;
16: 1–9.
21.
Pérez-CamposSJChavarría-HernándezNTecanteAet al.
Gelation and microstructure of dilute gellan solutions with calcium ions. Food Hydrocolloid2012;
28: 291–300.
22.
ShimizuMBrennerTLiaoRet al.
Diffusion of probe polymer in gellan gum solutions during gelation process studied by gradient NMR. Food Hydrocolloid2012;
26: 28–32.
23.
HorinakaJIKaniKHoriYet al.
Effect of pH on the conformation of gellan chains in aqueous systems. Biophys Chem2004;
111: 223–227.
24.
FunamiTNodaSNakaumaMet al.
Molecular structures of gellan gum imaged with atomic force microscopy (AFM) in relation to the rheological behavior in aqueous systems in the presence of sodium chloride. Food Hydrocolloid2009;
23: 548–554.
25.
WhittakerLEAl-RuqaieIMKasapisSet al.
Development of composite structures in the gellan polysaccharide/sugar system. Carbohyd Polym1997;
33: 39–46.
26.
EvageliouVGerolemouAZikasAet al.
Effect of salts and sugars on the clarity of gellan gels. Int J Food Sci Technol2011;
46: 1001–1006.
27.
DaiLLiuX andTongZ.Critical behavior at sol–gel transition in gellan gum aqueous solutions with KCl and CaCl2 of different concentrations. Carbohyd Polym2010;
81: 207–212.
SharmaS andBhattacharyaS.Strain and strain rate dependence of gellan, agar and agar-gellan gels as model systems. J Food Eng2014;
141: 93–98.
30.
MiyazakiSKawasakiNKuboWet al.
Comparison of in situ gelling formulations for the oral delivery of cimetidine. Int J Pharm2001;
220: 161–168.
31.
KuboWMiyazakiS andAttwoodD.Oral sustained delivery of paracetamol from in situ-gelling gellan and sodium alginate formulations. Int J Pharm2003;
258: 55–64.
32.
Remuñán-LópezCPorteroAVila-JatoJLet al.
Design and evaluation of chitosan/ethylcellulose mucoadhesive bilayered devices for buccal drug delivery. J Control Release1998;
55: 143–152.
33.
CarlforsJEdsmanKPeterssonRet al.
Rheological evaluation of Gelrite® in situ gels for ophthalmic use. Eur J Pharm Sci1998;
6: 113–119.
34.
KesavanKNathG andPanditJ.Preparation and in vitro antibacterial evaluation of gatifloxacin mucoadhesive gellan system. Daru2010;
18: 237–246.
35.
CaoSLRenWZhangZet al.
In situ gel based on gellan gum as new carrier for nasal administration of mometasone furoate. Int J Pharm2009;
365: 109–115.
36.
MahajanHS andGattaniSG.Gellan gum based microparticles of metoclopromide hydrochloride for intranasal delivery: development and evaluation. Chem Pharm Bull (Tokyo)2009;
57: 388–392.
37.
El-KamelA andEl-KhatibM.Thermally reversible in situ gelling carbamazepine liquid suppository. Drug Deliv2006;
13: 143–148.
38.
CencettiCBelliniDPavesioAet al.
Preparation and characterization of antimicrobial wound dressings based on silver, gellan, PVA and borax. Carbohyd Polym2012;
90: 1362–1370.
39.
KhangGLeeSKKimHNet al.
Biological evaluation of intervertebral disc cells in different formulations of gellan gum-based hydrogels. J Tissue Eng Regen Med2015;
9: 265–275.
40.
ChangSJHuangYTYangSTet al.
In vitro properties of gellan gum sponge as the dental filling to maintain alveolar space. Carbohyd Polym. 2012;
88: 684–689.
41.
ChangSJKuoSMLiuWTet al.
Gellan gum films for effective guided bone regeneration. J Med Biol Eng2010;
30: 99–103.
42.
GoyalRTripathiSKTyagiSet al.
Gellan gum blended PEI nanocomposites as gene delivery agents: evidences from in vitro and in vivo studies. Eur J Pharm Biopharm2011;
79: 3–14.
43.
WenYYangXHuGet al.
Direct electrochemistry and biocatalytic activity of hemoglobin entrapped into gellan gum and room temperature ionic liquid composite system. Electrochim Acta2008;
54: 744–748.
44.
ValentaC.The use of mucoadhesive polymers in vaginal delivery. Adv Drug Deliv Rev2005;
57: 1692–1712.
45.
LudwigA.The use of mucoadhesive polymers in ocular drug delivery. Adv Drug Deliv Rev2005;
57: 1595–1639.
46.
MarquesMRCLoebenbergR andAlmukainziM.Simulated biological fluids with possible application in dissolution testing. Dissolut Technol2011;
18: 15–28.
47.
BenjaminOSilcockPBeauchampJet al.
Volatile release and structural stability of β-lactoglobulin primary and multilayer emulsions under simulated oral conditions. Food Chem2013;
140: 124–134.
48.
PatelP andPatelP.Formulation and evaluation of clindamycin HCL in situ gel for vaginal application. Int J Pharm Investig2015;
5: 50–56.
NittaY andNishinariK.Gelation and gel properties of polysaccharides gellan gum and tamarind xyloglucan. J Biol Macromol2005;
5: 47–52.
51.
A-SasutjaritRSirivatA andVayumhasuwanP.Viscoelastic properties of carbopol 940 gels and their relationships to piroxicam diffusion coefficients in gel bases. Pharm Res2005;
22: 2134–2140.
52.
ChuJSYuDMAmidonGLet al.
Viscoelastic properties of polyacrylic acid gels in mixed solvents. Pharm Res1992;
9: 1659–1663.
53.
SmithTJKennedyEJ andHigginbothamCL.Rheological and thermal characteristics of a two phase hydrogel system for potential wound healing applications. J Mater Sci2010;
45: 2884–2891.
54.
MezgerTG.The rheology handbook: for users of rotational and oscillatory rheometers. 2nd ed.
Hannover:
Vincentz Network GmbH & Co KG, 2006.
55.
TakoMTeruyaTTamakiYet al.
Molecular origin for rheological characteristics of native gellan gum. Colloid Polym Sci2009;
287: 1445–1454.
56.
ClarkAH andRoss-MurphySB. Structural and mechanical properties of biopolymer gels. In: Biopolymers. Advances in polymer science, vol. 83. Berlin, Heidelberg: Springer, 1987, pp.57–192.
57.
NishinariK.Some thoughts on the definition of a gel. In: TokitaM andNishinariK (eds) Gels: Structures, properties, and functions. Progress in colloid and polymer science,
vol.136.
Berlin, Heidelberg:
Springer, 2009, pp.87–94.
58.
AmbortDJohanssonMEVGustafssonJKet al.
Calcium and pH-dependent packing and release of the gel-forming MUC2 mucin. Proc Natl Acad Sci USA2012;
109: 5645–5650.
59.
HägerströmHPaulssonM andEdsmanK.Evaluation of mucoadhesion for two polyelectrolyte gels in simulated physiological conditions using a rheological method. Eur J Pharm Sci2000;
9: 301–309.
