通过纳米胶囊改善胞壁酰二肽类似物的细胞内递送。

Improved intracellular delivery of a muramyl dipeptide analog by means of nanocapsules.

作者信息

Morin C, Barratt G, Fessi H, Devissaguet J P, Puisieux F

机构信息

URA CNRS 1218, Physico-Chimie, Pharmacotechnie, Biopharmacie, Université de Paris Sud, Faculté de Pharmacie, Chatenay-Malabry, France.

出版信息

Int J Immunopharmacol. 1994 May-Jun;16(5-6):451-6. doi: 10.1016/0192-0561(94)90035-3.

DOI:10.1016/0192-0561(94)90035-3

Abstract

A lipophilic derivative of muramyl dipeptide, muramyl tripeptide cholesterol, was incorporated into poly(D,L-lactide) nanocapsules and its immunomodulating properties were assessed in vitro. The nanocapsule form was more effective than the free drug in activating rat alveolar macrophages for a cytostatic effect toward syngeneic tumor cells. Induction of NO synthase correlated with anti-proliferative activity. The time course of activation and the effect of inhibitors of endocytosis suggested that this increased efficiency was due to improved intracellular delivery by phagocytosis of nanocapsules. Such nanocapsules might be useful for immunotherapy of metastases resistant to conventional treatment, since they could overcome two problems associated with soluble muramyl peptides: rapid elimination and poor uptake by macrophages.

摘要

将一种胞壁酰二肽的亲脂性衍生物——胞壁酰三肽胆固醇，包裹于聚（D，L-丙交酯）纳米胶囊中，并在体外评估其免疫调节特性。纳米胶囊形式在激活大鼠肺泡巨噬细胞以对同基因肿瘤细胞产生细胞抑制作用方面比游离药物更有效。一氧化氮合酶的诱导与抗增殖活性相关。激活的时间进程和内吞作用抑制剂的作用表明，这种效率的提高是由于纳米胶囊被吞噬后改善了细胞内递送。这种纳米胶囊可能对传统治疗耐药的转移瘤免疫治疗有用，因为它们可以克服与可溶性胞壁酰肽相关的两个问题：快速清除和巨噬细胞摄取不良。

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