Freie Universität Berlin, Pharmacology and Toxicology, Berlin, Germany.
Handb Exp Pharmacol. 2024;284:389-411. doi: 10.1007/164_2023_696.
High molecular weight actives and cell-based therapy have the potential to revolutionize the prophylaxis and therapy of severe diseases. Yet, the size and nature of the agents - proteins, nucleic acids, cells - challenge drug delivery and thus formulation development. Moreover, off-target effects may result in severe adverse drug reactions. This makes delivery and targeting an essential component of high-end drug development. Loading to nanoparticles facilitates delivery and enables targeted mRNA vaccines and tumor therapeutics. Stem cell therapy opens up a new horizon in diabetes type 1 among other domains which may enhance the quality of life and life expectancy. Cell encapsulation protects transplants against the recipient's immune system, may ensure long-term efficacy, avoid severe adverse reactions, and simplify the management of rare and fatal diseases.The knowledge gained so far encourages to widen the spectrum of potential indications. Co-development of the active agent and the vehicle has the potential to accelerate drug research. One recommended starting point is the use of computational approaches. Transferability of preclinical data to humans will benefit from performing studies first on validated human 3D disease models reflecting the target tissue, followed by studies on validated animal models. This makes approaching a new level in drug development a multidisciplinary but ultimately worthwhile and attainable challenge. Intense monitoring of the patients after drug approval and periodic reporting to physicians and scientists remain essential for the safe use of drugs especially in rare diseases and pave future research.
高分子量活性物质和基于细胞的疗法有可能彻底改变严重疾病的预防和治疗。然而，这些药物的大小和性质——蛋白质、核酸、细胞——给药物输送带来了挑战，也因此给制剂开发带来了挑战。此外，脱靶效应可能导致严重的药物不良反应。这使得输送和靶向成为高端药物开发的重要组成部分。将药物装载到纳米颗粒中有助于输送，并使靶向 mRNA 疫苗和肿瘤治疗成为可能。干细胞疗法在 1 型糖尿病等领域开辟了新的前景，可能提高生活质量和预期寿命。细胞封装可以保护移植免受受体免疫系统的攻击，确保长期疗效，避免严重的不良反应，并简化对罕见和致命疾病的管理。迄今为止获得的知识鼓励扩大潜在适应症的范围。活性药物和载体的共同开发有可能加速药物研究。一个推荐的起点是使用计算方法。将临床前数据转化为人类数据将受益于首先在经过验证的反映目标组织的人类 3D 疾病模型上进行研究，然后在经过验证的动物模型上进行研究。这使得在药物开发方面达到一个新的水平成为一个多学科的挑战，但最终是值得的和可实现的。药物批准后对患者进行密集监测，并定期向医生和科学家报告，对于安全使用药物，特别是在罕见疾病方面，仍然是至关重要的，为未来的研究铺平了道路。
