BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 TEM of nanoparticles Release properties of diblock particles 000000 Tine(days) 6. Release profles of BSA from PLGA(O Increased t in blood: Altered biodistribution 当125 日 PLGA Nanoparticles a PEG-PLGA Nanoparticles 0.75 型0.5 06888 5025 0 in。 20 Time after intravenous injection (hr) Fig. 7. Blood clearance curves of [I]BSA in PLGA (O)and PEG-PLGA(O) nanoparticle (Li et aL., 2001) uncloaking PEGylated carriers Use of cleavable PEG-carrier linkages to 'unmask carrier at selected site/time Allow full drug activity at site of action Example stealth'Carriers in clinical Use4, 5 Pegademase(Dagen o Pegylated adenosine deaminase(enzyme) Treatment of severe combined immunodeficiency(SCID)-hereditary lack of adenosine deaminase Pegaspargase(Oncaspar o Pegylated asparaginase(enzyme) o Treatment of leukemia Leukaemic cells cannot synthesize asparagines: asparaginase kills cells by depleting extracellular sources of this amino acid Pegylated IFN-a2a(Pegasys) o Treamtent of hepatitis c Doxil(Alza) o Pegylated liposomes carrying anti-cancer drug doxorubicin o Improves treatment from daily 30min injections for 5 days every 3 weeks to once-a-month single injections o Approved for treatment of Karposi's sarcoma Lecture15-‘ stealth’ particles 7 of 8BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 15 – ‘stealth’ particles 7 of 8 (Li et al., 2001) TEM of nanoparticles Release properties of diblock particles Increased t1/2 in blood: Altered biodistribution: uncloaking PEGylated carriers ƒ Use of cleavable PEG-carrier linkages to ‘unmask’ carrier at selected site/time ƒ Allow full drug activity at site of action ƒ Example: ‘Stealth’ Carriers in Clinical Use4,5 ƒ Pegademase (Adagen) o Pegylated adenosine deaminase (enzyme) o Treatment of severe combined immunodeficiency (SCID)- hereditary lack of adenosine deaminase ƒ Pegaspargase (Oncaspar) o Pegylated asparaginase (enzyme) o Treatment of leukemia ƒ Leukaemic cells cannot synthesize asparagines; asparaginase kills cells by depleting extracellular sources of this amino acid ƒ Pegylated IFN-α2a (Pegasys) o Treamtent of hepatitis C ƒ Doxil (Alza) o Pegylated liposomes carrying anti-cancer drug doxorubicin o Improves treatment from daily 30min injections for 5 days every 3 weeks to once-a-month single injections o Approved for treatment of Karposi’s sarcoma