Sulfonamide Based Polymeric Systems for Cancer Tumors

This monograph focuses on the design and study of
innovative polymeric drug delivery systems for
acidic solid cancer tumors. A sulfonamide-based pH-
sensitive polymer was developed to mask conventional
delivery systems such as gene carrier and polymeric
micelles, during systemic circulation and unmask
them at the acidic tumor. First a pH-sensitive
polymer (PSD-b-PEG) was evaluated in a gene delivery
model. Plasmid DNA was complexed with PEI, this
further complexed with PSD-b-PEG to construct a
nanoparticle. The nanoparticles showed low
cytotoxicity (20%) and low transfection at pH 7.4
due to shielding of PEI by PSD-b-PEG and high
cytotoxicity (80%) and high transfection at pH 6.6,
indicating deshielding. This indicated PSD-b-PEG''s
ability to discern the difference in pH between
normal and tumor tissue. Next DOX loaded micelles
using PSD-b-PEG were designed. Evaluation of the DOX
loaded PMCs in tumor bearing mice showed tumor
regression up to 33 days compared to 12 days for
regular DOX micelles.A new pH sensitive polymer,
PCBS-b-PEG, was developed next. This polymer was not
only able to mimic the PSD-b-PEG but was
biodegradable as well.

Autorentext

Dr. Vijay Sethuraman was born in Madurai, India. With a doctorate in Pharmaceutics and Pharmaceutical Chemistry , he is currently a senior scientist at Novartis Pharmaceuticals and lives with his wife in San Francisco, California. Dr. You Han Bae has been a full professor at the University of Utah at Salt Lake City, Utah since 2002.

Klappentext

This monograph focuses on the design and study of innovative polymeric drug delivery systems for acidic solid cancer tumors. A sulfonamide-based pH-sensitive polymer was developed to mask conventional delivery systems such as gene carrier and polymeric micelles, during systemic circulation and unmask them at the acidic tumor. First a pH-sensitive polymer (PSD-b-PEG) was evaluated in a gene delivery model. Plasmid DNA was complexed with PEI, this further complexed with PSD-b-PEG to construct a nanoparticle. The nanoparticles showed low cytotoxicity (20%) and low transfection at pH 7.4 due to shielding of PEI by PSD-b-PEG and high cytotoxicity (80%) and high transfection at pH 6.6, indicating deshielding. This indicated PSD-b-PEG's ability to discern the difference in pH between normal and tumor tissue. Next DOX loaded micelles using PSD-b-PEG were designed. Evaluation of the DOX loaded PMCs in tumor bearing mice showed tumor regression up to 33 days compared to 12 days for regular DOX micelles.A new pH sensitive polymer, PCBS-b-PEG, was developed next. This polymer was not only able to mimic the PSD-b-PEG but was biodegradable as well.