Hydrogel from Linum usitatissimum L.: Isolation, modification, characterization and pharmaceutical applications.

Abstract

Linseed hydrogel (LSH) was isolated from linseeds (Linum usitatissimum L.) using hot water extraction method, characterized and used in various formulation designs. Characterization of LSH was carried out using Fourier transform infrared (FTIR), powdered X-ray diffraction (PXRD), nuclear magnetic resonance (NMR), scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). LSH was also modified by acetylation and structures obtained were thoroughly characterized. Stimuli responsive swelling of LSH was evaluated at gastrointestinal pHs (1.2, 6.8 and 7.4) and in deionized water and also in different molar concentrations of NaCl and KCl solutions. Swelling-deswelling (on-off) response of LSH against environmental conditions was also observed. LSH has shown high swelling at pH 6.8, 7.4 and deionized water while negligible swelling was seen at pH 1.2 indicating potential of LSH as intestine targeting drug delivery system. Swelling behaviour of LSH at various pHs of gastrointestinal tract (GIT) has followed the second order kinetics. Inverse relation between swelling of LSH and molar concentrations (0.1, 0.2, 0.3, 0.4, 0.5, 1.0 and 2.0 M) of NaCl and KCl were observed. Moreover, the water swollen LSH when immersed in normal saline, shrinking was observed. A more abrupt shrinking of water swollen LSH was observed on immersing in ethanol. Similarly, swelling-deswelling response was also observed in buffer of pH 7.4 and 1.2, respectively. These results have revealed that LSH is a smart material and can be used to make intelligent drug delivery systems. High swelling and water holding capability of LSH were used to develop the sustained release formulation of diclofenac sodium. Drug release data from LSH tablets was compared with commercially available product (Voltral®) and found better results. It was observed that the release of diclofenac sodium from LSH matrix tablets was dependent on the concentration of LSH and followed the anomalous transport mechanism. Therefore, LSH can be used as a release retarding agent in sustained release formulation. LSH-caffeine and LSH-diacerein tablets were prepared to analyze the stimuli (pH, salt solution and ethanol) responsive swelling and swelling-deswelling (pH 7.4/1.2, water/normal saline and water/ethanol) behaviour of LSH when used in tablet formulation. Although, stimuli responsive properties of LSH remain the same even after compression in tablet form but less swelling capacity was observed after compression. This might be due to the packing arrangements of LSH and also less exposed area to the swelling medium in tablet form as compared to powder form. LSH appeared as a novel material for stimuli responsive and pH dependent release of NSAIDs in gastrointestinal tract. The elongated porous structure arranged in uniformly distributed layers were seen in FE SEM analysis of swollen then freeze dried powder sample of LSH. Similar pattern of porous channels was also observed even in tablet formulations of LSH. High swelling and water holding capability of LSH are due to these porous channels. Docetaxel loaded LSH Pluronic F-68 nanoparticles (DLP-NPs) were synthesized by core shell formation. Drug loaded core of LSH was protected and stabilized by Pluronic F-68. Size and morphological analysis of DLP-NPs was performed by dynamic light scattering (DLS), PXRD and TEM. Results indicated that DLP-NPs are spherical in shape having size range of 220-335 nm. In vitro drug release study has shown a prolong release pattern for more than 4 days. Cell viability study of LSH and DLP-NPs has proved even better results when compared with free docetaxel. Cell uptake behaviour of DLP-NPs was monitored using Nile red and high concentration of DLP-NPs was accumulated in the cytoplasmic region of the cell. Therefore, DLP-NPs have shown a promising anticancer drug delivery system. LSH was used as a reducing and capping agent for the green synthesis of Ag NPs. Aqueous suspension of LSH were mixed with silver nitrate solution and exposed to sunlight. Formation of Ag NPs was monitored by noting the colour of solution and through UV spectrophotometer. UV absorptions were observed from 410-437 nm. TEM images revealed the formation of spherical Ag NPs in the range of 10-35 nm. Face centered cubic array of Ag NPs was confirmed by characteristic diffraction peaks in PXRD spectrum. Significant antimicrobial activity was observed when microbial cultures (bacteria and fungi) were exposed to the synthesized Ag NPs. Wound healing studies revealed that Ag NPs impregnated in LSH thin films could have potential applications as an antimicrobial dressing in wound management procedures. Acute toxicity study of LSH was conducted on albino mice and albino rabbits. Three groups of mice were exposed to a single oral dose of LSH (1, 5 and 10 g/kg). For eye irritation study and dermal toxicity study, rabbits were exposed to LSH. After day 14, the haematological and biochemical testing were performed and the values obtained were within the normal range. Furthermore, the histopathological evaluation of the vital organs has not shown any abnormalities. After acute toxicity study, LSH was found safe up to the dose of 10g/kg of the body weight of the animal. Overall, LSH has shown itself as a highly swellable and smart biomaterial having stimuli responsive swelling-deswelling properties both in powder form and tablet formulation. Furthermore, the preparation of DTX loaded LSH NPs has proved its utilization in the development of novel drug delivery system for cancer treatment. Ag NPs embedded LSH matrix is a new biocomposite for wound dressing and wound healing. Therefore, LSH has proved as a potential material with wide range of pharmaceutical applications.