In‐vivo Testing of Coated Hydroxypropylmethylcellulose Granules Containing an Antineoplastic Glycan (PS4) Using Caco‐2 Tumour Cells
1996
Complex polysaccharides (glycans) with antineoplastic activity have previously been isolated from Mycobacterium tuberculosis and attenuated M. bovis (Bacillus Calmette Guerin, BCG vaccine). This present communication reports the formulation and activity of a new antineoplastic glycan isolated from M. vaccae, a rapidly growing non-virulent organism which may offer an alternative source of these potentially useful immunopotentiators.
The formulation consisted of a Eudragit S-100-coated hydroxypropylmethylcellulose (HPMC) granule that is believed from a parallel investigation to target the colorectal region of the gastrointestinal tract of the rat. No in-vitro activity of PS4 could be detected against the human colon adenoma Caco-2 cell line growing on collagen in tissue culture. However, when Caco-2 cells were implanted into the flanks of athymic nude mice, growth was initially slow but tumours could be palpated and measured in most animals 28 days after implantation. A preliminary experiment comparing 5-flurouracil and PS4 suggested that both materials were effective antineoplastics but scatter around the means rendered the data statistically insignificant. Refinement of the experiment by selecting only those animals in which tumours could be palpated at 28 days improved the reproducibility. Doses of 1 or 10 μg/mouse PS4 were administered by direct injection of a solution into the mouse flank or by oral intubation of a suspension of the coated HPMC granules at 28 days and again at 42 days post-implantation. Measurement of the tumour sizes for a further 42 days demonstrated that there was significant inhibition of the tumour growth rate relative to that of the control group (n = 7) at a dose of 10 μg/mouse, and a significant decrease in tumour size at 1 μg/mouse. There was no significant difference due to the route of administration.
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