Polymeric drug conjugates

Poly-(L)-Glutamic Acid-Paclitaxel (CT-2103) [XYOTAXT , a Biodegradable Polymeric Drug Conjugate... 

Zalipsky, S., Seltzer, R., and Nho, K. (1991) Succinimidyl carbonates of polyethylene glycol Useful reactive polymers for preparation of protein conjugates. In Polymeric Drugs and Drug Delivery Systems (R.L. Dunn, and R.M. Ottenbrite, eds.), pp. 91-100. American Chemical Society, Washington, D.C. 

Figure 1.3. Structure of PKl (HPMA copolymer doxorubicin), a 28-kDa polymeric carrier-drug conjugate investigated for its anti-tumour activity in a phase I clinical study. Adapted from reference [15].

The MTT assay was initially developed as a quantitative assay for cell survival and proliferation, not as an in vitro assay for chemosensitivity testing. Further study was required to ascertain if the method accurately predicted the in vivo antitumor activities of anticancer agents. Shimoyama et al. [189] studied the predictability of the MTT assay with respect to a clonogenic assay (Sect. 4.1.1.3.) and showed excellent reproducibility and a close correlation to the in vivo predictability rate of the clonogenic assay. Another study [190] also showed that the MTT assay closely approximated (90%) the clinical activity of anticancer agents. Many authors have since utilized the MTT assay to determine the efficacy of polymeric anticancer drug conjugates. 

The above mentioned effects were observed with different inert polymeric carriers. The results obtained with HPMA copolymer-drug conjugates are discussed in Sect. 5.3., the decrease of the immunogenicity of proteins after PEG modification in Sec. 2.1.1.1. 

Polymer-based delivery systems (Fig. 11.1) include polymer-protein conjugates, polymer-drug conjugates, micelles consisting of polymeric surfactants, and complexes of cationic polymers and DNA (polyplexes).26... 

This is an extension of the polymeric drug concept in which the drug can be conjugated to a polymeric matrix and... 

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