NAHA, a Novel Hydroxamic Acid-Derivative, Inhibits Growth and Angiogenesis of Breast Cancer In Vitro and In Vivo

BACKGROUND: We have recently synthesized novel N-alkylated amino acid-derived hydroxamate, 2-[Benzyl-(2-nitro-benzenesulfonyl)-amino]-N-hydroxy-3-methyl-N-propyl-butyramide (NAHA). Here, we evaluate the anticancer activity of NAHA against highly invasive human breast cancer cells MDA-MB-231 in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Cell growth was evaluated by MTT and soft agar assays. Protein expression was determined by DNA microarray and Western blot analysis. Metastatic potential was evaluated by cell adhesion, migration, invasion, capillary morphogenesis, and ELISA assays. The anticancer activity in vivo was evaluated in mouse xenograft model. NAHA inhibited proliferation and colony formation of MDA-MB-231 cells together with the down-regulation of expression of Cdk2 and CDC20 proteins. NAHA inhibited cell adhesion, migration, and invasion through the suppression of secretion of uPA. NAHA suppressed secretion of VEGF from MDA-MB-231 cells and inhibited capillary morphogenesis of human aortic endothelial cells (HAECs). Finally, NAHA at 50 mg/kg was not toxic and decreased tumor volume and tumor weight in vivo. This suppression of tumor growth was associated with the inhibition of mitotic figures and induction of apoptosis, and the reduction of CD31 and VEGF positive cells in tumors. CONCLUSION: NAHA could be a novel promising compound for the development of new drugs for the therapy of invasive breast cancers

Glyceryl Laurate Tablets: Effect of the Excipients and Granule Size on the Tablet Quality

Glyceryl laurate (GL) is a natural or synthetic surfactant with antiviral and antimicrobial activity and is not only effective in common colds or flu, but also against swine flu, herpes simplex, shingles, or chronic fatigue. The study aimed to formulate the GL granules as a semi-product for the compression of tablets and evaluate the influence of the substitution of sucrose laurate (Ryoto®) with sucrose ester (Sisterna®) in the composition of the granules and the effect of granule size on the quality of the compressed tablets. Four types of granules, varying in grain size and the type of additional surfactant, were prepared by melt granulation. The traditional pharmacopoeia tests were used to assess tablets’ quality. The granule size significantly affected all evaluated parameters: hardness, uniformity of mass, friability, and disintegration. The replacement of sucrose laurate with sucrose ester caused a slight decrease in tablet strength and a shortening of disintegration. However, it did not significantly impact friability and uniformity of mass. For this reason, the excipient, sucrose ester, can be evaluated as an adequate replacement in the composition of GL tablets

Technological Processing of Dried Powdered Rosehips to Tablets Through Wet Granulation

The pseudo-fruits of Dog Rose are a rich source of L-ascorbic acid and several other active substances, which means their high supportive therapeutic potential. The study aimed to examine the impact of the chosen technological procedure for the preparation of tablets containing rosehip powder on the amount of L-ascorbic acid in the final pharmaceutical form. Drying of the plant drug was performed at room temperature to avoid possible thermal degradation of this heat-sensitive compound. Similarly, drying of the granules after wet granulation in the oven was replaced by natural drying at room temperature. The composition of two types of prepared granule formulations differed in the filler – lactose (LAC) or microcrystalline cellulose (MCC). Apart from the disintegration test, they meet the technological requirements for granules or tablets. Lactose was confirmed as a more suitable filler, which despite the unsuccessful disintegration of the granules, ensures the disintegration of tablets within 15 minutes even without the addition of a special excipient acting as a disintegrant. The content of L-ascorbic acid detected using isotachophoresis – capillary zone electrophoresis was 87.16 ± 5.06 µg in LAC tablets and 63.33 ± 2.83 µg in MCC tablets