Many of new chemical discovered in pharmaceutical industry are hydrophobic compounds. Various techniques have been used to overcome solubility problems of hydrophobic drugs in aqueous media. In the meantime, dendrimers have been considered for sustainability, nanoscale size, high carry capacity, tunable terminal functional groups in terms of drug delivery and solubility. In this work, we have synthesized poly(propylene imine) (PPI) dendrimer up to fifth generation using reduction of nitrile groups after Michael addition and also, polyamidoamine (PAMAM) dendrimer up to fourth generation using Michael addition and amidation reactions. fourth and fifth generations of PPI dendrimer and fourth and third generations of PAMAM dendrimer in different concentrations were used to evaluate the solubility of two hydrophobic drugs (tetracycline and dexamethasone). Furthermore, cytotoxicity of dendrimers and dendrimers/drugs hybrids was studied. The results showed that with increasing concentrations and also the generation of dendrimers, the solubility of these two hydrophobic drugs was increased. Cytotoxicity study through MTT assay against Osteoblast‐like cell line (MG‐63 cells) showed that dendrimers were relatively cytotoxic where adding dexamethasone caused higher cytotoxicity. However, tetracycline showed no significant effect on cytotoxicity whereas prevented cell proliferation.

中文翻译：

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聚（丙烯亚胺）和聚酰胺胺树枝状大分子对四环素和地塞米松溶解度改善的比较研究：对细胞毒性和细胞增殖的洞察。

制药工业中发现的许多新化学物质都是疏水性化合物。已使用多种技术来克服疏水性药物在水性介质中的溶解性问题。同时，树枝状大分子因其可持续性、纳米级尺寸、高承载能力、在药物递送和溶解性方面的可调末端官能团而被考虑。在这项工作中，我们使用迈克尔加成后的腈基还原合成了高达第五代的聚（丙烯亚胺）（PPI）树枝状聚合物，并且使用迈克尔加成和酰胺化反应合成了高达第四代的聚酰胺胺（PAMAM）树枝状聚合物。用不同浓度的第四代和第五代PPI树枝状聚合物和第四代和第三代PAMAM树枝状聚合物来评价两种疏水性药物（四环素和地塞米松）的溶解度。此外，研究了树枝状聚合物和树枝状聚合物/药物杂交体的细胞毒性。结果表明，随着浓度的增加和树枝状大分子的产生，这两种疏水性药物的溶解度增加。通过 MTT 测定对成骨细胞样细胞系（MG-63 细胞）的细胞毒性研究表明，树枝状大分子具有相对的细胞毒性，而添加地塞米松会导致更高的细胞毒性。然而，四环素对细胞毒性没有显着影响，而能阻止细胞增殖。结果表明，随着浓度的增加和树枝状大分子的产生，这两种疏水性药物的溶解度增加。通过 MTT 测定对成骨细胞样细胞系（MG-63 细胞）的细胞毒性研究表明，树枝状大分子具有相对的细胞毒性，而添加地塞米松会导致更高的细胞毒性。然而，四环素对细胞毒性没有显着影响，而能阻止细胞增殖。结果表明，随着浓度的增加和树枝状大分子的产生，这两种疏水性药物的溶解度增加。通过 MTT 测定对成骨细胞样细胞系（MG-63 细胞）的细胞毒性研究表明，树枝状大分子具有相对的细胞毒性，而添加地塞米松会导致更高的细胞毒性。然而，四环素对细胞毒性没有显着影响，而能阻止细胞增殖。