ABSTRACT

Introduction

Therapeutic enzymes are currently used in the treatment of several diseases. In most cases, the benefits are limited due to poor in vivo stability, immunogenicity, and drug-induced inactivating antibodies. A partial solution to the problem is obtained by masking the therapeutic protein by chemical modifications. Unfortunately, this is not a satisfactory solution because frequent adverse events, including anaphylaxis, can arise.

Area covered

Among the delivery systems, we focused on red blood cells for the delivery of therapeutic enzymes. Erythrocytes possess a long circulation time, a reduced immunogenicity, there is no need of chemical modifications and the encapsulated enzyme remains active because it is protected by the cell membrane. Here we discuss some representative applications of the preclinical developments of the field. Some of these are currently in clinic, others are approaching the clinic and others are illustrative of the development process. The selected examples are not always the most recent, but they are the most useful for a comparative approach.

Expert opinion

The results discussed confirm the central role that red blood cells can play in the treatment of several conditions and suggest the benefit in using a natural cellular carrier in terms of pharmacokinetic, biodistribution, safety, and efficacy.

中文翻译：

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负载酶的红细胞的临床前开发。

摘要

介绍

治疗性酶目前用于治疗几种疾病。在大多数情况下，由于体内稳定性，免疫原性和药物诱导的失活抗体较差，因此收益受到限制。通过化学修饰掩盖治疗性蛋白，可以部分解决该问题。不幸的是，这不是令人满意的解决方案，因为可能会出现频繁的不良事件，包括过敏反应。

覆盖面积

在输送系统中，我们集中于红细胞输送治疗性酶。红细胞的循环时间长，免疫原性降低，不需要化学修饰，并且被包囊的酶保持活性，因为它被细胞膜保护。在这里，我们讨论该领域临床前开发的一些代表性应用。其中一些目前在诊所中，其他一些正在诊所中，其他一些则说明了开发过程。所选示例并非总是最新的，但对于比较方法而言它们是最有用的。

专家意见

讨论的结果证实了红细胞可以在多种疾病的治疗中发挥核心作用，并从药代动力学，生物分布，安全性和有效性方面提出了使用天然细胞载体的益处。