State Univ Paraiba, Grad Program Pharmaceut Sci, Rua Juvencio Arruda S-N, BR-58429600 Campina Grande, Paraiba, Brazil;Univ Sao Paulo, Dept Pharmaceut & Biochem Technol, Av Prof Linen Prestes 580,Bloco 16,Cidade Univ, BR-05508000 Sao Paulo, Brazil;Genoa Univ, Dept Civil Chem & Environm Engn, Chem Engn Pole, Via Opera Pia 15, I-16145 Genoa, Italy;Univ Sao Paulo, Dept Pharmaceut & Biochem Technol, Av Prof Linen Prestes 580,Bloco 16,Cidade Univ, BR-05508000 Sao Paulo, Brazil;Univ Fed Campina Grande, Dept Agrarian & Exact Sci, Postgrad Program Agroind Syst, Campus 4 UEPB, Pombal, Paraiba, Brazil;Univ Sao Paulo, Dept Pharmaceut & Biochem Technol, Av Prof Linen Prestes 580,Bloco 16,Cidade Univ, BR-05508000 Sao Paulo, Brazil;
Medeiros de Brito, Anna Emmanuela;Pessoa, Adalberto, Jr.;Converti, Attilio;Rangel-Yagui, Carlota de Oliveira;da Silva, Jose Alexsandro;Apolinario, Alexsandra Conceicao;
L-Asparaginase (ASNase) is an amidohydrolase used as a chemotherapeutic agent for the treatment of acute lymphoblastic leukemia (ALL). The nanoencapsulation of this enzyme is strategic to avoid its immediate immunogenic effects that lead to a decrease in the enzyme half-life. In this work, ASNase-containing nanoparticles (NPs) were prepared by double emulsification, through an ultrasonic sonicator or an Ultra-Turrax, using two copolymers of 50:50 (w/w) poly (lactic-co-glycolic acid) (PLGA) with different ranges of molecular weight (24-38 kDa and 30-60 kDa) and varying the concentration of polyvinyl alcohol (PVA) as a stabilizer (0.5, 1.0, 1.5 and 2.0%) as well as the emulsification time (30 and 60 s). Using 24-38 kDa PLGA and 1.0% PVA, we obtained by cavitation NPs with hydrodynamic diameter of 384 nm, polydispersity index of 0.143 and Zeta potential of -16.4 mV, whose ASNase encapsulation efficiency was as high as 87 +/- 2%. The encapsulated enzyme showed an activity 22% higher than that of the free enzyme, and no conformational changes were detected by circular dichroism. The enzyme release from NPs entrapped in dialysis bags (500 kDa molecular weight cut-off) allowed selecting a controlled system able to release about 60% of the enzyme within 14 days, for which the Korsmeyer-Peppas model provided the best correlation (R-2 = 0.966).