Immunotoxicology Research Group, Department of Pharmacology, National University of Colombia, Bogotá, Colombia.
Immunopharmacol Immunotoxicol. 2013 Jun;35(3):321-8. doi: 10.3109/08923973.2013.768635. Epub 2013 Mar 11.
Owing to its biocompatibility properties and its ability to promote the scar healing process, chitosan is employed in tissue engineering for the manufacture of formulations. To control the characteristic skin ulcers of cutaneous leishmaniasis (CL), the use of a biopolymeric system that favors the scar healing process and releases an active agent such as meglumine antimoniate may be a better option. For these reasons, here we analyzed the cytotoxic capabilities of excipients [medium molecular weight chitosan (MMWC), lactic acid (LA) and polyvinylpyrrolidone (PVP)], used for the formulation of a film-based therapeutic system that releases meglumine antimoniate and were evaluated on human macrophages [monocyte-derived macrophages (MDMs)], L929 fibroblasts and parasites (Leishmania major promastigotes and intracellular amastigotes). The ability of excipients to modulate the cytokines production involved in the scar healing process was compared with film-based therapeutic system. The efficiency of a film-based therapeutic system loaded with meglumine antimoniate was compared with conventional formulation (Albiventriz(®)). We found that MMWC was toxic for two parasite forms. In contrast, measurement of interleukin levels did not show any evidence of preferential secretion as a side effect of treating human macrophages with MMWC. Finally, the efficiency of a polymeric film-based therapeutic system that was loaded with meglumine antimoniate could not be determined due to the high degree of toxicity observed in infected MDMs; moreover, these compounds do not induce any apparent immunomodulatory effects. Our findings suggest that the final concentrations of each excipients (MMWC, LA and PVP) that were used in the polymeric film were suitable vehicles for active pharmaceutical compound delivery and did not selectively affect (enhancing or diminishing immune activity) macrophages.
由于其生物相容性和促进疤痕愈合过程的能力，壳聚糖被用于组织工程制造配方。为了控制皮肤利什曼病（CL）的特征性皮肤溃疡，使用有利于疤痕愈合过程并释放活性物质如葡甲胺锑的生物聚合物系统可能是更好的选择。出于这些原因，我们在这里分析了用于制备释放葡甲胺锑的基于膜的治疗系统的赋形剂（中分子量壳聚糖（MMWC）、乳酸（LA）和聚乙烯吡咯烷酮（PVP））的细胞毒性能力，并在人巨噬细胞（单核细胞衍生的巨噬细胞（MDMs））、L929 成纤维细胞和寄生虫（利什曼原虫前鞭毛体和细胞内无鞭毛体）上进行了评估。赋形剂调节参与疤痕愈合过程的细胞因子产生的能力与基于膜的治疗系统进行了比较。载有葡甲胺锑的基于膜的治疗系统的效率与常规制剂（Albiventriz（®））进行了比较。我们发现 MMWC 对两种寄生虫形式都有毒。相比之下，白细胞介素水平的测量没有显示出任何偏向性分泌的证据，这是用 MMWC 处理人巨噬细胞的副作用。最后，由于观察到感染的 MDMs 中存在高度毒性，因此无法确定载有葡甲胺锑的聚合物基于膜的治疗系统的效率；此外，这些化合物不会诱导任何明显的免疫调节作用。我们的研究结果表明，聚合物膜中使用的每种赋形剂（MMWC、LA 和 PVP）的最终浓度适合作为活性药物化合物的输送载体，并且不会选择性地影响（增强或减弱免疫活性）巨噬细胞。
