Synthesis and Characterization of Acrylamide/Acrylic Acid Co-Polymers and Glutaraldehyde Crosslinked pH-Sensitive Hydrogels

This project aims to synthesize and characterize the pH-sensitive controlled release of 5-fluorouracil (5-FU) loaded hydrogels (5-FULH) by polymerization of acrylamide (AM) and acrylic acid (AA) in the presence of glutaraldehyde (GA) as a crosslinker with ammonium persulphate as an initiator. The formulation’s code is named according to acrylamide (A1, A2, A3), acrylic acid (B1, B2, B3) and glutaraldehyde (C1, C2, C3). The optimized formulations were exposed to various physicochemical tests, namely swelling, diffusion, porosity, sol gel analysis, and attenuated total reflection-Fourier transform infrared (ATR-FTIR). These 5-FULH were subjected to kinetic models for drug release data. The 5-FU were shown to be soluble in distilled water and phosphate buffer media at pH 7.4, and sparingly soluble in an acidic media at pH 1.2. The ATR-FTIR data confirmed that the 5-FU have no interaction with other ingredients. The lowest dynamic (0.98 ± 0.04% to 1.90 ± 0.03%; 1.65 ± 0.01% to 6.88 ± 0.03%) and equilibrium swelling (1.85 ± 0.01% to 6.68 ± 0.03%; 10.12 ± 0.02% to 27.89 ± 0.03%) of formulations was observed at pH 1.2, whereas the higher dynamic (4.33 ± 0.04% to 10.21 ± 0.01%) and equilibrium swelling (22.25 ± 0.03% to 55.48 ± 0.04%) was recorded at pH 7.4. These findings clearly indicated that the synthesized 5-FULH have potential swelling characteristics in pH 6.8 that will enhance the drug’s release in the same pH medium. The porosity values of formulated 5-FULH range from 34% to 62% with different weight ratios of AM, AA, and GA. The gel fractions data showed variations ranging from 74 ± 0.4% (A1) to 94 ± 0.2% (B3). However, formulation A1 reported the highest 24 ± 0.1% and B3 the lowest 09 ± 0.3% sol fractions rate among the formulations. Around 20% drug release from the 5-FULH was found at 1 h in an acidic media (pH1.2), whereas >65% of drug release (pH7.4) was observed at around 25 h. These findings concluded that GA crosslinked 5-FU loaded AM and AA based hydrogels would be a potential pH-sensitive oral controlled colon drug delivery carrier.

Synthesis of Novel Tamarind Gum-co-poly(acrylamidoglycolic acid)-Based pH Responsive Semi-IPN Hydrogels and Their Ag Nanocomposites for Controlled Release of Chemotherapeutics and Inactivation of Multi-Drug-Resistant Bacteria

In this paper, novel pH-responsive, semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers were synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels were used as templates for the green synthesis of silver nanoparticles (13.4 ± 3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as a reducing agent. Swelling kinetics and the equilibrium swelling behavior of the TMGA hydrogels were investigated in various pH environments, and the maximum % of equilibrium swelling behavior observed was 2882 ± 1.2. The synthesized hydrogels and silver nanocomposites were characterized via UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels were investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapsulation efficiency, i.e., 69.20 ± 1.2, was used in in vitro release studies in pH physiological and gastric environments at 37 °C. The drug release behavior was examined with kinetic models such as zero-order, first-order, Higuchi, Hixson Crowell and Korsmeyer–Peppas. These release data were best fitted with the Korsemeyer–Peppas transport mechanism, with n = 0.91. The effects of treatment on HCT116 human colon cancer cells were assessed via cell viability and cell cycle analysis. The antimicrobial activity of TMGA-Ag hydrogels was studied against Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and the inactivation of pathogenic bacteria, respectively.

Synthesis of Novel Tamarind Gum-co-Poly(Acrylamidoglycolic Acid) based pH Responsive semi-IPN Hydrogels and their Ag Nanocomposites for Controlled Release of Chemotherapeutics and Inactivation of Multi Drug Resistance Bacteria

Novel pH responsive semi-interpenetrating polymer hydrogels based on tamarind gum-co-poly(acrylamidoglycolic acid) (TMGA) polymers have been synthesized using simple free radical polymerization in the presence of bis[2-(methacryloyloxy)ethyl] phosphate as a crosslinker and potassium persulfate as a initiator. In addition, these hydrogels have been used as templates for green synthesis of silver nanoparticles (13.4±3.6 nm in diameter, TMGA-Ag) by using leaf extract of Teminalia bellirica as reducing agent. Swelling kinetics and equilibrium swelling behavior of the TMGA hydrogels have been investigated in various pH environment the maxium % equilibrium swelling behavior observed i.e., 2882±1.2. The synthesized hydrogels and silver nanocomposites have been characterized by the UV, FTIR, XRD, SEM and TEM. TMGA and TMGA-Ag hydrogels have been investigated to study the characteristics of drug delivery and antimicrobial study. Doxorubicin hydrochloride, a chemotherapeutic agent successfully encapsulated with maximum encapulstaion efficiency i.e., 69.20±1.2 and performed in vitro release studies in pH physiological and gastric environment at 37 ℃. The drug release behavior is examined with kinetic models such as zero order, first order, Higuchi, Hixson Crowell, Korsmeyer-Peppas. These release data was the best fitted with the Korsemeyer-Peppas transport mechanism with n=0.91. Treatment effect on HCT116 Cell, human colon cancer cells were assessed with cell viability and cell cycle analysis. Antimicrobial activity of TMGA-Ag hydrogels is studied against to Staphylococcus aureus and Klebsiella pneumonia. Finally, the results demonstrate that TMGA and TMGA-Ag are promising candidates for anti-cancer drug delivery and inactivation of pathogenic bacteria, respectively.

Effect of pH and temperature on swelling Behaviour of tamarind gum

Natural gum tamarind is a plant polysaccharide extracted from seeds endosperm of the plant, Tamarindus indica Linn. Thin film of the gum was prepared by direct compression method. The prepared film was investigated for the effect of pH and temperature on solvent uptake property of film by gravimetric method. Different swelling parameters such as mass swelling ratio (MSR), equilibrium swelling ratio (ESR), equilibrium swelling ratio (ESw) and the equilibrium water content (EWC) were studied. It was found that swelling parameters were influenced by different pH and temperature conditions. The results suggested that the water content in equilibrium state was similar to body fluid. The gum converted to a high viscous gel of pseudo plastic characteristics in different pH conditions and the mechanism of continuous diffusion of solvent molecules into tablet during swelling was a non fickian and followed a second order kinetics.

Competition between Osmotic Squeezing versus Friction-Driven Swelling of Gels

Some types of hydro-gels have almost the same equilibrium swelling volume in water and in ethylene glycol (EG), a highly viscous liquid completely miscible with water. Experiments showed that when a gel fully swollen with EG is immersed into a large amount of water, it temporarily swells up and then relaxes to the equilibrium volume in water. The temporary swelling is explained by the friction force exerted on the gel network from the outward EG flux In this paper, we experimentally show that the temporary swelling is suppressed by adding linear PEG (polyethylene glycol) in the outer water. Although the suppression seems to be explained by the osmotic pressure (i.e., by the same mechanism as the conventional osmotic squeezing), our theoretical analysis reveals that the effect of PEG is much stronger than that expected from the equilibrium osmotic pressure, implying that the PEG chains are condensed on the gel surface.

Experimental Verification of the Balance between Elastic Pressure and Ionic Osmotic Pressure of Highly Swollen Charged Gels

The equilibrium swelling degree of a highly swollen charged gel has been thought to be determined by the balance between its elastic pressure and ionic osmotic pressure. However, the full experimental verification of this balance has not previously been conducted. In this study, we verified the balance between the elastic pressure and ionic osmotic pressure of charged gels using purely experimental methods. We used tetra-PEG gels created using the molecular stent method (St-tetra-PEG gels) as the highly swollen charged gels to precisely and separately control their network structure and charge density. The elastic pressure of the gels was measured through the indentation test, whereas the ionic osmotic pressure was determined by electric potential measurement without any strong assumptions or fittings. We confirmed that the two experimentally determined pressures of the St-tetra-PEG gels were well balanced at their swelling equilibrium, suggesting the validity of the aforementioned relationship. Furthermore, from single-strand level analysis, we investigated the structural requirements of the highly swollen charged gels in which the elasticity and ionic osmosis are balanced at their swelling equilibrium.