L-asparaginase immobilization in supramolecular nanogels of PEG-grafted poly HPMA and bis(α-cyclodextrin) to enhance pharmacokinetics and lower enzyme antigenicity.
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| 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.
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| Authors | Maryam Monajati, Ali Mohammad Tamaddon, Samira Sadat Abolmaali, Gholamhossein Yousefi, Sanaz Javanmardi, Sedigheh Borandeh, Reza Heidari, Negar Azarpira, Rassoul Dinarvand |
| Journal | Colloids and surfaces. B, Biointerfaces (Colloids Surf B Biointerfaces) Vol. 225 Pg. 113234 (May 2023) ISSN: 1873-4367 [Electronic] Netherlands |
| PMID | 36934612 (Publication Type: Journal Article) |
| Copyright | Copyright © 2023. Published by Elsevier B.V. |
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