Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4 minutes) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded PLGA nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model. Here we demonstrate the influence of PLGA polymer, stabilizer loading and molecular weight as well as sonication time on the characteristics, including DSF release and the cytotoxicity of 10% w/w DSF-loaded PLGA nanoparticles. The paper demonstrates that the choice of PLGA as no significant influence on the characteristics of the nanoparticles apart from their DSF release, which is due to the differing degradation rates of the polymers. However, increasing the loading and molecular weight of the stabilizer as well as the sonication time reduced the size of the nanoparticles, reduced their ability to protect the DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity. Additionally, increasing the sonication time resulted in the premature degradation of the PLGA, which increased the permeability of the nanoparticles further decreasing their ability to protect DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity.

The present work aimed at design and development of subcutaneous implantable drug delivery systems containing progesterone for continuous administration of drug to promote estrus synchronization. With the help of Galaxy extruder the implants were fabricated by extrusion method using polymers ethyl cellulose, cellulose acetate and their combination. The prepared implants were characterized for diameter, uniformity of weight, drug content uniformity, sterility testing, short term stability study and in vivo histopathological study. The in vitro release study in phosphate buffer pH 7.4 at 37 0 C was conducted from the implant matrix as function of concentration of the polymers in implants formulations over a period of 14 to 21 days. The progesterone implants having high polymer concentration releasing less amount of the incorporated drug, compared to drug released from implants having low polymer concentration. Thus polymer concentration effectively controls the amount of drug released. Short term stability of progesterone implants revealed that the implants formulations were stable, and there were no significant changes in physical appearance and drug content of the implants formulations. In vivo histopathological study of prepared progesterone implants in rabbits shows that the polymers used in implants are compatible with the tissues. Data suggest that the implants prepared from cellulose acetate and ethyl cellulose would be promising and interesting non-biodegradable systems for sustained delivery of progesterone for livestock.

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