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Transcript 
Chitosan
Polymer
Science
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
1953
Staudinger’s Nobel
Prize
Polymer
Science
Watson and Crick’s
theory about the
structure of DNA
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
Mescaline-N-vinylpyrolidine conjugate
• One of the first polymer-drug conjugates
Polymer
Science
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
Polymer
Science
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
http://www.nektar.com/wt/page/advanced_pegylation
Polymer
Science
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
Polymer
Science
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
HPMA copolymer conjugate of doxorubicin
• Treats cancer
PEG-α-interferon
• Treats chronic hepatitis C and hepatitis B
Albumin-entrapped paclitaxel
• Treats metastatic breast cancer
Polymer
Science
Cancer and
hepatitis
treatment
PEGylation
Polymer-drug
conjugates
EPR
Advantages
Increased protein solubility and stability
Reduced protein immunogenicity
Prolonged plasma half-life
Compound
Status
Indications
PEG-adenosine deaminase
Market
SCID syndrome
PEG-l-asparaginase
Market
Acute lymphoblastic leukaemia
PEG-GCSF
Market
Prevention of neutropaenia associated
with cancer chemotherapy
PEG-α-interferon 2a
Market / Phase I/II
PEG-α-interferon 2b
Market / Phase I/II
PEG-arginine deiminase
Phase I
Hepatitis B and C / Melanoma, chronic
myeloid leukaemia and renal-cell
carcinoma
Hepatitis C / Melanoma, multiple
myeloma and renal-cell carcinoma
Hepatocellular carcinoma
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-camptothecin
Phase II
Various cancers.
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-camptothecin
Phase II
Various cancers.
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-camptothecin
Phase II
Various cancers.
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-camptothecin
Phase II
Various cancers.
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-camptothecin
Phase II
Various cancers.
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-α-camptothecin
Phase II
Various cancers.
Polymer-drug conjugates
Compound name
Status
Indications
HPMA copolymer-doxorubicin
Phase II
Various cancers, particularly lung and breast
cancer
HPMA copolymer-doxorubicingalactosamine
Phase I/II
Particularly hepatocellular carcinoma.
HPMA copolymer-camptothecin
Phase I
Various cancers.
HPMA copolymer-paclitaxel
Phase I
Various cancers.
HPMA copolymer-carboplatin
platinate
Phase I/II
Various cancers.
HPMA copolymer-DACH-platinate
Phase I/II
Various cancers.
PGA-paclitaxel
Phase III
Various cancers, particularly non-small cell lung
cancer; ovarian cancer
PGA-camptothecin
Phase I/II
Various cancers.
Dextran-doxorubicin
Phase I
Various cancers.
Modified dextran-camptothecin
Phase I
Various cancers.
PEG-camptothecin
Phase II
Various cancers.
Particular characteristics
Biocompatibility
Biodegradability
Low toxicity
Stability
Particular characteristics
Biocompatibility
Biodegradability
Low toxicity
Stability
Particular characteristics
Biocompatibility
Biodegradability
Low toxicity
Stability
Particular characteristics
Biocompatibility
Biodegradability
Low toxicity
Stability
Particular characteristics
Biocompatibility
Biodegradability
Low toxicity
Stability
Chitosan
Glucosamine Units
A free amino group
Hyaluronic Acid
D-glucuronic acid
N-acetylglucosamine
Dextran
Polysaccharide
Derived from sucrose
Gellan
High molecular
weight
Exopolysaccharide
(EPS)
Theory
• Progress
Practice
• Toxicity
• Clinical
Testing
Prof. Leonilde Moreira
• DEQB (IST)
Duncan, R. 2003. The dawning era of polymer therapeutics. Nat Rev Drug Discov
2:347-60.
Biotechnology. PEGylation. Accessed in November, 26, 2008. Biotecnology:
http://www.biology.iupui.edu/biocourses/Biol540/3DrugCaseStudies2k7.htm
Duncan, R. 2006. Polymer conjugates as anticancer nanomedicines. Nat Rev Cancer
6:688-701.
Duncan, R., H. Ringsdorf, and R. Satchi-Fainaro. 2006. Polymer therapeutics polymers as drugs, drug and protein conjugates and gene delivery systems: past,
present and future opportunities. J Drug Target 14:337-41.
Duncan, R. 2007. Designing polymer conjugates as lysosomotropic nanomedicines.
Biochem Soc Trans 35:56-60.
J. Vinsova and E. Vavrikova. 2008. Recent Advances in Drugs and Prodrugs Design of
Chitosan. Current Pharmaceutical Design, 14: 1311-1326
Kogan, G., L. Soltes, R. Stern, and P. Gemeiner. 2007. Hyaluronic acid: a natural
biopolymer with a broad range of biomedical and industrial applications. Biotechnol
Lett 29:17-25.
Arsenio M. Fialho, Leonilde M. Moreira, Ana Teresa Granja, Alma O. Popescu, Karen
Hoffmann and Isabel Sá-Correia. 2008. Occurrence, production, and applications of
gellan: current state and perspectives. Appl Microbiol Biotechnol. 79:889–900.
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