Synthesis Of Gum Tragacanth-Cl-Poly (Acrylic Acid) Superabsorbent Hydrogels with Salt, pH and Electrical Responsive Properties
Department of Pharmacy, MN DAV Dental College, Solan, 173212 (H.P), India
Received: 14-May-2017 , Accepted: 10-Oct-2017
Keywords: Colon specific targeting, Hydrogel, Glutaraldehyde, Salt resistant, Electrical responsive properties
How To Cite
The Gum tragacanth-acrylic acid-based hydrogels were prepared using KPS-ascorbic acid as an initiator and glutaraldehyde as crosslinker via free radical graft copolymerization technique. Synthesized polymers were characterized with FTIR, SEM and thermal techniques in order to authenticate the grafting of poly (AA) on to Gum tragacanth. The candidate’s hydrogel was also evaluated for salt resistant distension studies by means of biological electrolytic system using AC/DC supply. Moreover, the re-swelling ability of the candidate polymer was also studied using different pH media for its utilization in the site specific drug delivery. The results of the study suggested that the candidate polymer shows good salt resistant behavior alongwith pulsatile (swelling/de-swelling) nature. From the results of present study it was concluded that thepolymer can beutilized for targeted drug delivery system as carrier.
Hydrogel formation is also known as the complexation of the polymers1,2. They are utilized in drug delivery3,4 system because of their unique capability of swelling under biological conditions alongwith immobilization of proteins, peptides and other therapeutically active compounds5. Properties of the swelling medium like pH 6, ionic strength7 and counter ions8 primarily affects the swelling characteristic of the hydrogel. Literature suggested that many studies have been carried out regarding the synthesis, characterization, controlled drug delivery and swelling behavior of different polymers in the past using different backbone and monomer9, 10.
Kaith et al.11 prepared a hydrogel by the introduction of arylic group in psyllium backbone i.e acrylated psyllium. The salt resistant swelling behavior of the hydrogel was studied along with the pH and temperature sensitivity. Kim et al.12 studied the poly(vinyl alcohol)/chitosan IPN hydrogels exhibiting electric sensitive behavior. They reported the stepwise bending behavior of IPN hydrogels depending on the electric stimulus. Further they reported that bending angle and bending speed of poly (vinyl alcohol)/chitosan IPN hydrogels increase with applied voltage and concentration of NaCl aqueous solution.
Osada et al.13 reported an electro-sensitive artificial muscle system working under isothermal conditions. Singh et al.14 synthesised psyllium based polymeric network and evaluated for swelling nature by including the parameters like temperature, pH and salt. Vandelli et al.15, Shu et al.16 developed a pH responsive chitosan based hydro gels drug release system. Krishnaiah et al.17 studied the influence of metronidazole and tinidazole on the usefulness of guar gum, a colon-specific drug carrier. Momin et al.18 carried in vitro studies scheduling colon-targeted delivery of sennosides a guar gum based formulation. Rubinstin et al.19 potentially developed the Chondroitin sulphate based ecological carrier for the colon-specific drug release.
Targeted liberation of the medicaments in colon is achievable only when the drug is secluded from the unreceptive environment of upper GIT. Colon specific drug targeting makes the hydrogel an appropriate carrier for the drug delivery in case of treatment of diseases such as Rheumatoid arthritis, ulcerative colitis, Chron`s disease, carcinomas, asthma and inflammation20,21. Moreover, the salt resistant swelling can be utilized in water treatment technology 11.
We planned to synthesized Gum tragacanth-acrylic acid based hydrogels using KPS-ascorbic acid and glutaraldehydes as an initiator-cross-linked via free radical graft copolymerization technique. Salt resistant studies on the swelling of candidate polymer using an artificial biological electrolytic system were carried out using AC/DC source. Moreover, the re-swelling ability of the candidate polymer was also studied using different pH media.
2 Materials and Methods
Gum tragacanth (S d Fine Chemicals Pvt. Ltd.) and ascorbic acid-potassium persulphate (S d Fine Chemicals Pvt. Ltd.) were used as backbone and initiator, respectively. Glutaraldehyde (MERCK) and acrylic acid (MERCK) were used as cross-linked and monomer, respectively.
2.1 Instrumental analysis
FTIR analysis of the back bone and cross-linked product was carried out on Perkin Elmer spectrophotometer using KBr pellets. Scanning Electron Micrographs of the polymers were taken on LEO-435VF, LEO Electron Microscopy Ltd. Thermal studies were carried-out on Perkin Elmer thermal analyzer at a heating rate of 10 °C/min in nitrogen atmosphere.
2.2 Synthesis of superabsorbent
1.0 g of Gum tragacanth was taken in a reaction flask containing 25 ml of distilled water. 0.5 mol L-1 of acrylic acid was added to the reaction mixture followed by the addition of ascorbic acid-KPS in 1:1.25 molar ratio as an initiating system and 0.42 mol L-1 of glutaraldehyde as a cross-linked. The reaction was carried out at pH 7.0 for 90 min at 40 °C.
At the end of the reaction, the homopolymer was removed on washing with hot water and synthesized gel was allowed to stand for about 10-12 hours undisturbed for gelling process to take place. The product obtained was dried in the oven at 60°C till a constant weight was obtained. The percentage grafting and percentage swelling were calculated as per the following equations 1:
Iw= initial weight of the material taken;
Fw = final weight of the material obtained
2.3 Salt resistant studies using DC / AC source
Apparatus used for the salt resistantsensitive studies is shown in the Fig. 1. The system consists of an inner compartment (20.5 × 15 × 10 cm), two copper electrodes (8 × 5.3 × 0.2 cm), a thermostat, thermometer, and an outer compartment (24.5 × 19 × 12 cm) acting as a closed system. Distance between two copper electrodes was about 15.5 cm. Pre-optimized and dried hydrogel was immersed in NaCl solution of different concentration (1%, 5%, 10%, 15% and 20%) at 37°C and 10V AC/DC source.
On the application of electrical stimulus, polymer shows swelling behavior and was weighed after a regular time interval. Percentage swelling (PS) was calculated by the equation 2:
Iup = initial weight of unswelled polymer;
Fsp = final weight of swelled polymer
2.4 Preparation of solutions of different pH
Alkaline solutions were prepared with NaOH pallets and acidic solutions were prepared by the addition of HCl and pH was determined with Cyberscan 1100, EUTECH INSTRUMENTS, pH meter (Fig 1).
3 Results and Discussions
For graft copolymerization to occur on the hydroxyl groups of the monomer alongwith the backbone acts as an active site. The steps implicated in the graft copolymerization of acrylic acid on Gum tragacanth are represented by the schematic diagram.
The ionic form of Ascorbic acid reacts with potassium persulphate to produce SO4-*. This on further reaction with H2O gives out OH*. Both the generated ionic forms (OH* and SO4-*) generate active site for grafting on reaction with backbone and monomer. In the presence of glutaraldehyde the activated monomer and backbone molecules proliferate and give rise to three dimensional cross-linked networks. Reaction between two activated chains or reaction of OH* with live propagating macromolecular chains results in chain termination.
To demarcate the morphological differences on the surface of both Gum tragacanth and Gt-cl-poly(AA) scanning electron micrographs (SEM) was implicated. Morphological changes in Gum tragacanth are quite evident after grafting and crosslinking. Fig 2b clearly showed that Gt-cl-poly(AA) has some cross-linked networks, whereas Gum tragacanth has a smooth and homogenous structure (Fig 2a).
3.2.2 FT-IR Spectroscopy
Broad peaks are obtained in the FTIR spectrum of Gum tragacanth at 3427.08 cm-1 (O-H stretching bonded absorption of carbohydrates), 2934.78 cm-1 (CH2 asymmetric stretching), 1039.07 cm-1 (C-O stretching region as complex bands, resulting from C-O and C-O-C stretching vibrations).
On the other hand, FTIR spectrum of Gt-cl-poly(AA) showed peaks at 2854.31 cm-1, 2659.42 cm-1 and 2521.73 cm-1 (O-H stretching of carboxylic acid). Additional peaks have been observed at 1750.23 cm-1 and 1613.40 cm-1 due to C=O stretching in carboxylic acid.
3.2.3 Thermal studies
Thermal studies of both the backbone and functionalized polymer were performed as a function of percent weight loss vs. temperature. In case of Gum tragacanth, three stage decompositions haveobserved (Fig 3a). Primary decomposition reactions due to dehydration were observed upto 170 °C. First stage decomposition has been observed from 170 °C – 473 °C with 64.1 % weight loss. Second stage decomposition started at 473 °C and continues upto 577 °C with 3.3 % weight loss. This is followed by decomposition initialized at 577°C and carried upto 644°C with 15.5% weight loss in the 3rd stage. The initial decomposition temperature (IDT) and final decomposition temperature (FDT) of Gum tragacanth was 170 °C and 644 °C respectively.
It has been found that Gt-cl-poly(AA) showed initial decomposition temperature near at 210 °C and final decomposition temperature at 560 °C (Fig 3b).
The crystalline structure of grafted poly(AA) with Gum tragacanth gets distorted due to morphological changes resulting in low thermal stability of Gt-cl-poly(AA). Gum tragacanth showed sharp exothermic peaks at 580 °C (143.8 μV) and 646 °C (87.9 μV). On the other hand, Gt-cl-poly(AA) showed exothermic peak at 514 °C (136.6 μV).
3.3 Effect of NaCl concentration on percentage swelling of biopolymer at 37 °C
It is evident from Fig 4 that the swelling capacity of candidate polymer in NaCl solution decreases with increasing NaCl concentration. Maximum swelling found at 1% NaCl solution is 216%. It is due to reverse osmosis process and in hypertonic solutions (higher concentration), the polymer shows shrinking behavior.
3.4 Effect of NaCl concentration on percentage swelling of biopolymer under the influence of 10V AC-source
It was observed from Fig 5 that the swelling capacity of candidate polymer in NaCl solution decreases with increasing NaCl concentration.Maximum swelling (332%) was found at 1% NaCl, which can be explained based on a reverse osmosis process. Moreover, under the influence of AC source, ion screening effect (similar ion repulsion) takes place, e and the candidate polymer shows higher percentage swelling in comparison with salt resistant swelling devoid of electric field.
3.5 Effect of NaCl concentration on percentage swelling of bio-polymer under the influence of 10V DC-source
It has been found from Fig 6 that the swelling capacity of candidate polymer in NaCl solution decreases with increasing NaCl concentration.Maximum swelling found at 1% NaCl solution is 330%. This can be explained based on reverse osmosis process and in hypertonic solutions (higher concentration), the polymer shows shrinking behavior. Moreover, under the influence of DC source, ion screening effect (similar ion repulsion) takes place, e and the candidate polymer shows higher percentage swelling in comparison with salt resistant swelling devoid of electric field.
3.6 Re-swelling ability of bio-polymer
Pulsatile behavior of bio-polymer was analyzed in solutions of different pH and percentage swelling was observed to be significantly affected (Fig 7). When the completely dried hydrogel sample is placed in the swelling medium of pH 9.2, the solvent diffuses into the outer surface of the candidate polymer through the micro-pores, results in the plasticization of macromolecular chains.
Simultaneously the ionization of –COOH results in –COO– ions generation resulting in the development of hydrated layer. This hydrated layer causes counter ions moment which cause the gel to swell. The dry core portions of the candidate polymer disappear and the matrix gel shows continuous swelling. The swelling is further enhanced due to relaxation of macromolecular chain. When the fully hydrated gel is placed in the medium of pH 2.0, H+ ions present in the external solution, diffuse into the gel matrix through water-filled macrospores that have existed in the fully hydrated gel. The de-swelling of polymer matrix occurs due to the folding of macromolecular chains. This occurs as a result of protonation (H+ ions) of –COO– group to yield uncharged –COOH groups.
Modification of Gum tragacanth via crosslinking and network formation with acrylic acid improves the property profile and usability of the polymer in various technical fields. Further, the product obtained was found to show salt resistant swelling, which could be of great importance in the purification of portable water, especially in coastal areas. The candidate polymer was found to show pulsatile behavior under acidic and basic conditions, which could be of great significance in the sustained release of colon specific drugs.
5 Conflict of interests
The author declared none
6 Author’s contributions
DP has carried out the research work in the laboratory, compiled and analyzed the data.
- Peppas NA, Khare AR. Preparation, structure and diffusional behavior of hydrogels in controlled release.Adv Drug Delivery Rev. 1993; 11: 1-35.
- Lee SH, Shin H. Matrices and scaffolds for delivery of bioactive molecules in bone and cartilage tissue engineering. Adv Drug Delivery Rev. 2007; 59(4-5): 339-359.
- Wakerly Z, Fell JT, Attwood D, Parkins DA. Pectin/ethylcellulose film coating formulations- For colonic drug delivery. J Pharm Pharmacol. 1997; 49: 1210.
- Ashford M, Fell J, Attwood D, Sharma H, Woodhead P. Studies on pectin formulations for colonic drug-delivery. J Control Rel. 1994; 30: 225-232.
- Chen X, Martin BD, Neubauer TK, Linhardt RJ, Dordick JS, Rethwich DG. Enzymatic and chemo enzymatic approaches to synthesis of sugar-based polymer and hydrogels. Carbohydr Polym. 1995; 28(1): 15-21.
- Casadei MA, Pitarresi G, Calabrese R, Paolicelli P, Giammona G. Biodegradable and pH-sensitive hydrogels for potential colon-specific drug delivery: characterization and in vitro release studies. Biomacromolecules 2008; 9(1): 43-49.
- Chiu HC, Wu AT, Lin YF. Synthesis and characterization of acrylic acid-containing dextran hydrogels. Polymer 2001; 42: 1471-1479.
- Gils PS, Ray D, Mohanta GP, Manavalan R, Sahoo PK. Designing of new acrylic based macroporous superabsorbent polymer hydrogel and its suitability for drug delivery. Int J Pharm Pharm Sci. 2009; 1: 44-54.
- Kaith BS, Jindal R, Mittal H.Superabsorbent hydrogels from poly (acrylamide-co-acrylonitrile) grafted Gum ghatti with salt, pH and temperature responsive properties. Der Chemica Sinica. 2010; 1(2): 92-103.
- Ganji F, Farahani EV.Hydrogels in Controlled Drug Delivery Systems, Iran Polym J.2009;18(1), 63-88.
- Singh B, Chauhan GS, Sharma DK, Kant A, Gupta I, Chauhan N. Int J Pharm. The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels. 2006; 325(1-2): 15-25.
- Vandelli MA, Leo E, Forni F, Bernatei MT. In vitro evaluation of a potential colonic drug delivery system that releases drug after a controllable lag-time. Eur J Pharm Biopharm. 1996; 43: 148-151.
- Shu XZ, Zhu KJ, Song W. Novel pH sensitive citrate crosslinked chitosan film for drug controlled release. Int J Pharm. 2001; 212(1):19-28.
- Krishnaiah YSR, Devi SA, Rao NL, Reddy, BPR, Karthikeyan RS, Satyanarayana V. Guar gum as a carrier for colon specific delivery; influence of metronidazole and tinidazole on invitro release of albendazole from guar gum matrix tablets. J Pharm Pharmaceut Sci. 2001; 4(3): 235-243.
- Momin M, Pundarikakshudu K. In vitro studies on guar gum based formulation for the colon targeted delivery of Sennosides. J Pharm Pharm Sci. 2004; 7(3): 325-331.
- Rubinstin A, Nakar D, Sintov A, Chondroitin sulphate: A potential biodegradable carrier for colon-specific drug delivery. Int J Pharm. 1992; 84: 141-150.
- Saffran M, Bedra C, Kumar GS, Neckers DC. Vasopressin: a model for the study of effects of additives on the oral and rectal administration of peptide drugs. J Pharm Sci. 1988; 77(1): 33-38.
- Mackay M, Tomlinson E. Colonic delivery of therapeutic peptides and proteins In: Colonic drug absorption and metabolism, Bieck, P. Eds., Marcel Dekker, New York,159-176, 1993.