Jain Keerti, Verma Ashwni Kumar, Mishra Prabhat Ranjan, Jain Narendra Kumar
Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. H. S. Gour Central University, Sagar, India; Pharmaceutical Nanotechnology Research Laboratory, ISF College of Pharmacy, Moga, India.
Pharmaceutics Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, India.
Nanomedicine. 2015 Apr;11(3):705-13. doi: 10.1016/j.nano.2014.11.008. Epub 2015 Jan 14.
This paper describes a novel strategy for targeted delivery of amphotericin B (AmB) to macrophages with muramyl dipeptide (MDP) conjugated multimeric poly(propyleneimine) (PPI) dendrimers. Synergistic antiparasitic activity due to immunostimulation by multimeric presentation of MDP on dendrimers was anticipated. MDP conjugated 5.0G PPI (MdPPI) dendrimers were synthesized and characterized. Therapeutic activity and toxicity of dendrimeric formulation of AmB (MdPPIA) were compared with marketed formulations of AmB. Highly significant (P<0.01) reduction in toxicity was observed in hemolytic toxicity and cytotoxicity studies in erythrocytes and J774A.1 macrophage cells, respectively. Formulation MdPPIA showed appreciable macrophage targeting potential and higher or equivalent antiparasitic activity against parasite infected macrophage cell lines and in vivo infection in Balb/c mice. These results suggest the developed MDP conjugated dendrimeric formulation of AmB as a promising immunostimulant targeted drug delivery system and a safer alternative to marketed formulations. From the clinical editor: Parasitic infections remain a significant issue in the clinical setting. The authors in this article studied the use of ligand anchored dendrimeric formulation of Amphotericin B to target infected macrophages and showed reduced toxicity, high anti-leishmanial activity. This may add another treatment option to available formulations in the future.
本文描述了一种用与胞壁酰二肽（MDP）偶联的多聚体聚（丙烯亚胺）（PPI）树枝状大分子将两性霉素B（AmB）靶向递送至巨噬细胞的新策略。预计由于树枝状大分子上MDP的多聚体呈递所产生的免疫刺激作用，会产生协同抗寄生虫活性。合成并表征了与MDP偶联的5.0G PPI（MdPPI）树枝状大分子。将AmB的树枝状制剂（MdPPIA）的治疗活性和毒性与市售的AmB制剂进行了比较。在红细胞和J774A.1巨噬细胞的溶血毒性和细胞毒性研究中，分别观察到毒性显著降低（P<0.01）。制剂MdPPIA对感染寄生虫的巨噬细胞系以及Balb/c小鼠体内感染显示出可观的巨噬细胞靶向潜力和更高或相当的抗寄生虫活性。这些结果表明，所开发的与MDP偶联的AmB树枝状制剂是一种有前景的免疫刺激靶向药物递送系统，也是市售制剂的更安全替代品。临床编辑评论：寄生虫感染在临床环境中仍然是一个重要问题。本文作者研究了用配体锚定的两性霉素B树枝状制剂靶向感染的巨噬细胞，结果显示毒性降低，抗利什曼原虫活性高。这可能会在未来为现有制剂增加另一种治疗选择。
