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L-Asparaginase Immobilization in Supramolecular Nanogels of Peg-Grafted Poly Hpma and Bis(Α-Cyclodextrin) to Enhance Pharmacokinetics and Lower Enzyme Antigenicity Publisher Pubmed



Monajati M1, 2 ; Tamaddon AM1, 2, 3 ; Abolmaali SS1, 2 ; Yousefi G2, 3 ; Javanmardi S2 ; Borandeh S2 ; Heidari R4 ; Azarpira N5 ; Dinarvand R6
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Source: Colloids and Surfaces B: Biointerfaces Published:2023


Abstract

L-asparaginase (ASNase) enzyme has limited therapeutic use due to its poor pharmacokinetics and immunogenicity. To overcome these obstacles, we immobilized ASNase in biocompatible poly hydroxypropyl methacrylamide (P(HPMA))-based nanogels simply formed through the host-guest inclusion complex of ASNase-conjugated random copolymer of HPMA and polyethylene glycol (PEG) acrylate (P(HPMA-MPEGA)) and α-cyclodextrin dimer (bisCD) using cystamine as a linker. The effects of bisCD and polymer concentrations on particle size, gelation time, and recovery of enzyme activity were investigated. The ASNase-conjugated bisCD nanogels were discrete, homogeneous, and spherical with a mean projected diameter of 148 ± 41 nm. ASNase immobilized in the bisCD nanogels caused cytotoxicity on HL-60 cell line with IC50 of 3 IU/ml. In-vivo rat study revealed that the immobilized ASNase reduced the enzyme antigenicity and resulted in 8.1 folds longer circulation half-life than the native enzyme. Conclusively, immobilization of ASNase in P(HPMA-MPEGA) and bisCD supramolecular nanogels could enhance the therapeutic value of ASNase in cancer chemotherapy. © 2023
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