(291g) Controlled Delivery of ABL in A NON-Cytotoxic REGULATION of Cancerous Cell Growth

The purpose of this work is to investigate the efficacy of ABL-loaded PLGA microspheres on the inhibition of tumor cells proliferation as a long term strategy to control the growth of a variety of cancer cell types. This strategy has the advantage over other chemical-based drugs currently used in terms of its significantly lower toxic side effects because ABL is a natural molecule obtained from mushrooms without any apparent cytotoxicity to normal and even cancerous cells. Based on the previously observed delivery rate of the different lactic to glycolic acid monomer ratio in PLGA, PLGA 5050DL was chosen as it has a 3-5 weeks release cycle. 2.5mg of ABL was encapsulated to ensure that the lowest functional concentration for controlling cancerous cell proliferation can be delivered by the PLGA. In this work, ABL as a drug is encapsulated in PLGA polymers in the form of microspheres. With this delivery method, even though ABL acts reversibly and will lose its efficacy over time, the lectin can still be used to control the growth of tumor cells for a longer period. However, this targeted anti-tumour effect does have to be reapplied when the encapsulated microspheres are depleted.

It was found that ABL can inhibit the proliferation of three different human cancer cell lines, Hep3B, KB and MCF-7, by controlling cell proliferation without being cytotoxic or killing the cells, while at the same time stimulating cell differentiation. The lectin was also found to have no effects on normal, non-cancerous cells like L929 or hMSCs, or non-human cancer cells like Neuro2a or C6 glioma cells. Therefore, an unorthodox method of controlling and limiting cancer growth through the use of ABL-encapsulated microspheres is proposed in this work, in contrast to conventional methods of killing cancer cells with cytotoxic treatments that have severe side effects. PLGA microspheres, being used as a long-term controlled release device, were thus found to prolong the therapeutic effect of ABL even at low concentrations for up to a month. Through the co-encapsulation studies, it was found that BSA was effective in protecting ABL from denaturation or degradation during the microsphere fabrication process. This system has therefore proven to be a successful drug-delivery vehicle that can overcome the limitations of ABL for cancer treatment applications.

The authors would like to acknowledge the funding by the National University of Singapore under the grant number R279000228112.