PMID- 36145567
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230918
IS  - 1999-4923 (Print)
IS  - 1999-4923 (Electronic)
IS  - 1999-4923 (Linking)
VI  - 14
IP  - 9
DP  - 2022 Aug 29
TI  - Peg-Grafted Liposomes for L-Asparaginase Encapsulation.
LID - 10.3390/pharmaceutics14091819 [doi]
LID - 1819
AB  - L-asparaginase (ASNase) is an important biological drug used to treat Acute 
      Lymphoblastic Leukemia (ALL). It catalyzes the hydrolysis of L-asparagine (Asn) 
      in the bloodstream and, since ALL cells cannot synthesize Asn, protein synthesis 
      is impaired leading to apoptosis. Despite its therapeutic importance, ASNase 
      treatment is associated to side effects, mainly hypersensitivity and 
      immunogenicity. Furthermore, degradation by plasma proteases and immunogenicity 
      shortens the enzyme half-life. Encapsulation of ASNase in liposomes, 
      nanostructures formed by the self-aggregation of phospholipids, is an attractive 
      alternative to protect the enzyme from plasma proteases and enhance 
      pharmacokinetics profile. In addition, PEGylation might prolong the in vivo 
      circulation of liposomes owing to the spherical shielding conferred by the 
      polyethylene (PEG) corona around the nanostructures. In this paper, ASNase was 
      encapsulated in liposomal formulations composed by 
      1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) or 
      1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) containing or not different 
      concentrations of 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N [methoxy 
      (polyethylene glycol)-2000] (DSPE-PEG). Nanostructures of approximately 142-202 
      nm of diameter and polydispersity index (PDI) of 0.069 to 0.190 were obtained and 
      the vesicular shape confirmed by Transmission Electron Microscopy (TEM and 
      cryo-TEM). The encapsulation efficiency (%EE) varied from 10% to 16%. All 
      formulations presented activity in contact with ASNase substrate, indicating the 
      liposomes permeability to Asn and/or enzyme adsorption at the nanostructures' 
      surface; the highest activity was observed for DMPC/DSPE-PEG 10%. Finally, we 
      investigated the activity against the Molt 4 leukemic cell line and found a lower 
      IC(50) for the DMPC/DSPE-PEG 10% formulation in comparison to the free enzyme, 
      indicating our system could provide in vivo activity while protecting the enzyme 
      from immune system recognition and proteases degradation.
FAU - de Souza Guimaraes, Marina
AU  - de Souza Guimaraes M
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Cachumba, Jorge Javier Muso
AU  - Cachumba JJM
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Bueno, Cecilia Zorzi
AU  - Bueno CZ
AUID- ORCID: 0000-0003-2365-5301
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Torres-Obreque, Karin Mariana
AU  - Torres-Obreque KM
AUID- ORCID: 0000-0003-1911-385X
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Lara, Grace Veronica Ruiz
AU  - Lara GVR
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Monteiro, Gisele
AU  - Monteiro G
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Barbosa, Leandro Ramos Souza
AU  - Barbosa LRS
AD  - Department of General Physics, Institute of Physics, University of Sao Paulo, Sao 
      Paulo 05508-000, SP, Brazil.
AD  - Brazilian Synchrotron Light Laboratory (LNLS), Brazilian Center for Research in 
      Energy and Materials (CNPEM), Campinas 13083-100, SP, Brazil.
FAU - Pessoa, Adalberto Jr
AU  - Pessoa A Jr
AUID- ORCID: 0000-0002-5268-8690
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
FAU - Rangel-Yagui, Carlota de Oliveira
AU  - Rangel-Yagui CO
AUID- ORCID: 0000-0003-4221-9505
AD  - Department of Biochemical and Pharmaceutical Technology, School of Pharmaceutical 
      Sciences, University of Sao Paulo, Sao Paulo 05508-000, SP, Brazil.
LA  - eng
GR  - 2013/08617-7, 2014/10456-4, 2015/15822-1, 2018/15104-0/Sao Paulo Research 
      Foundation/
GR  - 301832/2017-0, 309418/2021-6, 309224/2019-5/National Council for Scientific and 
      Technological Development/
GR  - 001/Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior/
PT  - Journal Article
DEP - 20220829
PL  - Switzerland
TA  - Pharmaceutics
JT  - Pharmaceutics
JID - 101534003
PMC - PMC9503594
OTO - NOTNLM
OT  - L-asparaginase
OT  - acute lymphoblastic leukemia
OT  - liposome
OT  - nanocarrier
OT  - nanoreactor
OT  - pegylated liposome
COIS- The authors declare no conflict of interest, financial or otherwise.
EDAT- 2022/09/24 06:00
MHDA- 2022/09/24 06:01
PMCR- 2022/08/29
CRDT- 2022/09/23 01:42
PHST- 2022/07/27 00:00 [received]
PHST- 2022/08/17 00:00 [revised]
PHST- 2022/08/24 00:00 [accepted]
PHST- 2022/09/23 01:42 [entrez]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2022/09/24 06:01 [medline]
PHST- 2022/08/29 00:00 [pmc-release]
AID - pharmaceutics14091819 [pii]
AID - pharmaceutics-14-01819 [pii]
AID - 10.3390/pharmaceutics14091819 [doi]
PST - epublish
SO  - Pharmaceutics. 2022 Aug 29;14(9):1819. doi: 10.3390/pharmaceutics14091819.