Biodegradable super porous inulin cryogels as potential drug carrier

Abstract

Here, chemically crosslinked super porous inulin cryogels were synthesized by the cryogelation method using divinyl sulfone (DVS) at various mol ratios of 75% to 150% inulin repeating units. Inulin cryogel prepared at 75 mol% DVS crosslinking showed a maximum swelling capacity of 1842 ± 159% in phosphate buffer saline (PBS, pH 7.4). The hydrolytic degradation of inulin cryogels prepared at different ratios were investigated at 37.5 Cat pH 1, 7.4, and 9. Depending on the degree of crosslinking, it was found that inulin cryogels were completely degraded in 1 to 6 days at pH 1, and the degradation continued at pH 7.4 and 9 for up to 21 days. Inulin cryogel with 75 mol% crosslinker had 61% ± 7% and 45% ± 2% weight losses at pH 7.4 and pH 9, respectively, at end of 21 days. Also, 75% crosslinked inulin cryogel was conjugated with amoxicillin trihydrate (AMX) drug and released 65.15 ± 5.35 mg/g of AMX at pH 1 at end of 24 hours. At pH 7.4 and 9, the AMX released amount were determined as 64.83 ± 6.19 and 55.57 ± 4.00 mg/g, respectively, in 120 hours. Furthermore, inulin cryogels were determined to be blood compatible materials via hemolytic tests with hemolysis ratio of 1.08% ± 0.14% and a blood clotting index of 80.67% ± 1.86%. K E Y W O R D S biodegradable polymer network, blood compatible drug carrier, inulin cryogel 1 | INTRODUCTION Inulin is a plant-based linear biopolymer naturally occurring in many plants such as chicory, asparagus, wheat, onion, garlic, banana, etc. It is an important agricultural by-product and commonly used in the food sector, drug transport systems, tissue engineering, pharmaceutical and cosmetic products. 1-5 In the food sector, it is used as dietary fiber to increase the nutritional value of products and is one of the most beneficial natural probiotics. 6-11 Additionally, inulin can be considered a renewable material in bioprocesses for biofuel production. The biocompatible, biodegradable, renewable, and hydrophilic structure, along with natural and plant-based origin, make inulin a very attractive material for diverse applications. 12-14 Cryogels are distinctive types of hydrogels with faster response time to external stimuli due to their highly macro porous interconnected matrices that can be obtained by crosslinking monomeric or polymeric precursors in the partially frozen phase under cryogenic conditions. 15,16 The size and the extent of pores in cryogels can be controlled by various parameters, for example, the amount of water, cooling rate, the reaction temperature, monomer/polymer concentration, the amount of crosslinker, the amount of catalyst, etc. 17-21 Ascryogels exhibit faster response time and mechanical strength compared to normal hydrogels, they offer many advantages in common applications including environmentally related, that is, separation, actuation, and sensors, tissue engineering and as cell carrier in biotechnology due to their super-porous structures. 22-27 Moreover, because it is possible to prepare cryogels from natural sources and they are biodegradable, they can...

Design and Assessment of Biodegradable Macroporous Cryogels as Advanced Tissue Engineering and Drug Carrying Materials

“…For example, the degradation rate of the HEMA-lactatedextran-co-NIPA scaffold increased with temperature due to the hydrolysis of lactate spacer and was higher for scaffolds with a large proportion of HEMA-lactate-dextran component [151]. The degradation of inulin cryogels was dependent on the concentration of cross-linker, DVS, and pH [85]. The degradation of inulin cryogels was examined in different buffer solutions to predict drug release properties of the materials under different biological conditions, such as pH 1, pH 7.4 and pH 9 and a temperature of 37.5 • C. The full degradation of inulin cryogels was observed at pH 1, and it took between one and six days depending on the degree of cross-linking.…”

“…Facilitates cancer cell invasion, migration and proliferation allowing for comprehensive characteristic of tumor cell behavior and testing the activity of anticancer drugs [29] Hyaluronic acid-PEG Immobilized biomimetic ligands offer control over cellular response resulting in enhanced spreading with RGD and formation of 3D cell spheroids with IKVAV [161] HEMA-Alginate-Gelatin 3D culturing of prostate cancer cells and spheroids to study their progression and behavior [188] Poly(ethylene glycol) diacrylate and type I collagen semi-interpenetrating polymer network cryogels Tunable off-the-shelf platforms for 3D cancer cell [112] Drug delivery HEMA-Gelatin pH-responsive release of doxorubicin with increased rate in more acidic conditions mimicking tumor environment [30] Inulin cryogel Release of amoxicillin trihydrate [85] Alginate beads Release of quercetin as antioxidant [19] Chitosan, hydroxyapatite, heparin, and polyvinyl alcohol composite Release of bone morphogenic protein 2 and support of the differentiation of rat bone marrow mesenchymal stem cells.…”

“…In vitro degradation is usually studied in a buffer or simulated biological media by analyzing the mass loss of the scaffold over time [ 48 , 85 , 151 ]. The simulated degradation conditions may involve chemical hydrolysis, such as in the case of PLLA scaffold [ 151 , 170 ], or induced by adding enzymes [ 69 ].…”

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“…Often, hydrolytically cleavable bonds such as simple and ester bonds are used to conjugate the drug with the matrix. These types of bonds provide a long-term drug release profile and increase the half-life of drugs in the body [60].…”

Synthesis and Characterization of Hierarchical Zeolites Modified with Polysaccharides and Its Potential Role as a Platform for Drug Delivery

“…Generally, there is little work involving the synthesis of porous materials modified with the aforementioned compounds. Examples of the synthesis of such materials were published by Ojeda et al [ 24 ] and Ari and Sahiner [ 25 ]. The first group proposed the synthesis of metal-modified mesoporous starches using a simple microwave-assisted method involving gelation of the parent polysaccharide and addition of the metal precursor, followed by solvent exchange and drying [ 24 ].…”