Nutritional chemoprevention is particularly suitable for prostate cancer. Gnetin C, a resveratrol dimer found abundantly in the melinjo plant (Gnetum gnemon), may possess more potent biological properties compared to other stilbenes. We examined the effects of gnetin C in a high-risk premalignant transgenic mouse model overexpressing tumor-promoting metastasis-associated protein 1 (MTA1) on the background of Pten heterozygosity (R26MTA1; Pten+/f; Pb-Cre+). Mice were fed diets supplemented with the following compounds: pterostilbene (70 mg/kg diet); gnetin C, high dose (70 mg/kg diet); and gnetin C, low dose (35 mg/kg diet). Prostate tissues were isolated after 17 weeks and examined for histopathology and molecular markers. Serum was analyzed for cytokine expression. Gnetin C-supplemented diets substantially delayed the progression of preneoplastic lesions compared to other groups. Prostate tissues from gnetin C-fed mice showed favorable histopathology, with decreased severity and number of prostatic intraepithelial neoplasia (PIN) foci, reduced proliferation, and angiogenesis. A decreased level of MTA1, concurrent with the trend of increasing phosphatase and tensin homolog expression and reduced interleukin 2 (IL-2) levels in sera, were also detected in gnetin C-fed mice. Importantly, gnetin C did not exert any visible toxicity in mice. Our findings demonstrate that a gnetin C-supplemented diet effectively blocks MTA1-promoted tumor progression activity in high-risk premalignant prostate cancer, which indicates its potential as a novel form of nutritional interception for prostate cancer chemoprevention.
In today’s world with increasing patient population, the demand for pharmaceutical medications is increasing enormously. However, poor solubility of drug substances and underdeveloped manufacturing process are affecting the revenue of the pharmaceutical industries. Improving the solubility and establishing a robust manufacturing process is the primary prerequisite of the developmental scientists. Among various approaches amorphous solid dispersion has gained a tremendous response for improving the solubility of the drug substances. In addition, the process of hot melt extrusion has attracted the investigators from regulatory agencies and industries. The process of hot melt extrusion involves application of thermal and mechanical energy on to the processing material. The process requires no solvent and is referred as “green technique.” Various factors need to be taken into consideration for developing amorph amorphous solid dispersions. The miscibility of drug and polymer, solubility of drug in polymer, drug-polymer interactions, glass transition temperature, storage conditions majorly influence the stability of the amorphous solid dispersions systems. Though hot melt extrusion is most widely employed for developing amorphous solid dispersions still a lot of research is warranted for developing strategies to formulate high drug loading medications with improved stability. This review article mainly focuses on the instrumentation, and process for developing amorphous solid dispersions by hot melt extrusion with a small note on the various advantages and limitations.
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