Chemotherapy based on HPMA copolymer conjugates with pH-controlled release of doxorubicin triggers anti-tumor immunity.

A novel class of anti-cancer therapeutics - polymeric conjugates of N-(2-hydroxypropyl)methacrylamide (HPMA) copolymers and doxorubicin with pH-controlled release of the drug - is highly efficient in killing tumor cells in vitro and is potent in eradicating growing tumors in vivo. Moreover, in comparison with low-molecular-weight drugs, the macromolecular therapeutics show decreased acute as well as delayed adverse side-toxicity. More importantly, the polymeric conjugates trigger the onset of specific anti-tumor immune response and this anti-tumor immunity can be transferred with splenocytes to naïve recipients.

Cytostatic and immunomobilizing activities of polymer-bound drugs: experimental and first clinical data.

An N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer carrier containing doxorubicin and human immunoglobulin as an actively/passively targeting moiety was used in four patients with generalized breast cancer resistant to standard cytotoxic chemotherapy. The dose and time schedule were deduced from a Phase I clinical trial in which doxorubicin bound to HPMA copolymer carrier (PK1) was tested. It was confirmed that the Dox-HPMA-HuIg conjugate is stable and doxorubicin remains in the peripheral blood with a small amount also in the urine, mostly in its polymer-bound form.

HPMA-hydrogels containing cytostatic drugs. Kinetics of the drug release and in vivo efficacy.

This study proposes a strategy to generate new anticancer therapy using hydrogel-based drug delivery systems to improve drug bioavailability and increase the therapeutic efficacy. We have synthesized biodegradable hydrogels based on N-(2-hydroxypropyl)methacrylamide (HPMA) with prolonged drug release. Pharmacokinetic data from in vitro studies showed that the in vitro release of hydrophilic drugs (doxorubicin, vinblastine) from HPMA-hydrogels is affected mainly by drug diffusion and only partially by hydrogel degradation.