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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.
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.