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.

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