University Lyon, University Claude Bernard Lyon 1, Laboratoire d'Automatique et de Génie des Procédés, LAGEP UMR CNRS 5007, F-69622 Villeurbanne, France.
Int J Pharm. 2012 Jul 1;430(1-2):207-15. doi: 10.1016/j.ijpharm.2012.03.025. Epub 2012 Mar 21.
The aim of the present work is to prepare nanoparticulate systems that can target and modulate the functions of mononuclear phagocytes by local administration. All-trans retinoic acid (RA) was chosen as an immunomodulator to be encapsulated in biodegradable nanoparticles (NP). Different formulations were prepared by the nanoprecipitation method and poly(d,l)lactic acid based nanocapsules (NC) were selected to continue the study. RA-NC demonstrated a sustained release profile and an enhanced stability for 7 days. The uptake of fluorescent (NileRed) labeled NP was conducted on bone marrow derived macrophages (BMM) in vitro and xenograft glioma nude mice in vivo. Fluorescent microscopy observations and flow cytometry analysis demonstrated that NR-NC were engulfed by BMM in vitro and lasted inside over 7 days. The intratumoral injection of NR-NC confirmed that NC were efficiently uptaken by infiltrated macrophages. The effects of RA loaded NC on BMM were also evaluated by RT(2)-PCR array. Our results suggest that polymeric nanoparticles are suitable carriers to deliver RA into macrophages and can offer a new strategy in tumor macrophage-based treatment.
本工作旨在通过局部给药制备能够靶向和调节单核吞噬细胞功能的纳米颗粒系统。全反式视黄酸（RA）被选择作为一种免疫调节剂，以包裹在可生物降解的纳米颗粒（NP）中。通过纳米沉淀法制备了不同的制剂，并选择聚（DL）丙交酯纳米胶囊（NC）继续研究。RA-NC 表现出持续释放的特征，并在 7 天内增强了稳定性。在体外骨髓来源的巨噬细胞（BMM）和体内异种移植神经胶质瘤裸鼠上进行了荧光（NileRed）标记的 NP 摄取实验。荧光显微镜观察和流式细胞术分析表明，NR-NC 在体外被 BMM 吞噬，并在体内持续超过 7 天。NC 的肿瘤内注射证实 NC 被浸润的巨噬细胞有效摄取。还通过 RT(2)-PCR 阵列评估了负载 RA 的 NC 对 BMM 的影响。我们的结果表明，聚合物纳米颗粒是将 RA 递送到巨噬细胞中的合适载体，并为基于肿瘤巨噬细胞的治疗提供了一种新策略。
