(351a) Fabrication of Superporous Cyclodextrin Cryogels Embedded Poly(cyclodextrin) Microgels

Antimicrobial resistance (AMR) occurs when germs like bacteria no longer respond to the drugs that are designed to kill them. Antimicrobial-resistant infections require frequent and therapeutic doses of drug administration. AMR especially threatens people receiving health care and those with weakened immune systems are often at higher risk of getting an infection. Extended drug release is advantageous to maintain a constant concentration of drug in plasma over a prolonged period to improve the therapeutic index of antibiotics. Therefore, polymeric micro/nano-carriers are found to be the most suitable system due to the tunable sizes, surface properties, modifiable properties, and biocompatible nature to attain desired drug release kinetics. Alpha (α-), beta (β-), and gamma (γ-) cyclodextrins (CDs) containing 6, 7, and 8 glucopyranose units, respectively, are natural macrocyclic molecules obtained from the biodegradation of starch. CDs can form inclusion complexes with a wide variety of drug molecules and improve their bioavailability. Earlier, we reported the polymeric particles of α-, β-, and γ-CDs as p(α-CD), p(β-CD), and p(γ-CD), respectively were synthesized by a one-step micro-emulsion polymerization method. Also, the corresponding cryogel networks of CDs via cryo-crosslinking polymerization technique were reported by our group. SEM analyses confirmed that p(CD) particles were spherical in the size range of a few hundred nanometers to tens of micrometers and p(CD) cryogels had interconnected homogeneous pore distribution with the pore sizes range of 5-100 µm. Polymeric CD-based microgels and their corresponding super porous cryogels up to 1.0 mg/mL concentrations were found to be biocompatible on L929 fibroblast cell line and hemocompatible on red blood cells. Here, p(α-, β-, γ-CD) microgels embedded within the superporous poly(α-, β-, γ-CD) cryogels were prepared and characterized. The biocompatibility studies of p(CD) based materials performed on L929 fibroblast cell line and hemocompatibility studies showed that p(CD) microgel embedding superporous p(CD) cryogels are highly biocompatible at 1.0 mg/mL concentrations. Moreover, two antibiotic drugs belonging to different classes of antibiotics separately were loaded into p(CD)microgel embedding superporous p(CD) cryogel and in vitro drug release studies were performed at physiological pH conditions (pH 7.4). It was found that the p(CD) cryogels embedding p(CD) microgel can afford a sustained drug release profile which can reduce dose frequency, AMR-related disease burden and antibiotic expenditure. Antibacterial activity of p(CD) microgel embedded p(CD) cryogels were tested also against Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa; and Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus.