Niven R W
Amgen, Inc., Thousand Oaks, CA 91320-1789, USA.
Crit Rev Ther Drug Carrier Syst. 1995;12(2-3):151-231. doi: 10.1615/critrevtherdrugcarriersyst.v12.i2-3.20.
The role of inhalation therapy is adapting to changes brought on by advances in several related disciplines. These range from device technology to the molecular and cell biology of the lungs. Acceptable bioavailability and efficacy have been achieved via the oral route for most traditional pharmaceuticals. Unfortunately, injection is the normal mode of delivery with biotherapeutic agents and alternative delivery approaches are needed. Many preclinical and clinical studies with inhaled proteins, peptides, and DNA have been completed and demonstrate that efficacy can be achieved within the lungs and systemically. Despite the promising results, the development of inhaled biotherapeutics is beset with unique problems that require an integrated and rational approach to development. Aqueous protein formulations are often not stable to aerosolization, while stability of powder formulations can be difficult to evaluate in the solid state. Inhaler efficiency and reproducibility are unacceptable with existing devices and, although improvements in technology have brightened the outlook, new devices are not yet available and remain untried with most biotherapeutics. Once delivered to the lungs, these molecules are also subjected to a variety of efficient clearance mechanisms that can significantly reduce the probability of them being effective. Despite these problems, the number of potential drugs being tested via inhalation continues to increase, suggesting some promise of future success. This review discusses the above issues and highlights a variety of biotherapeutics that have been administered as inhalation aerosols.
吸入疗法的作用正在适应几个相关学科进展所带来的变化。这些学科范围从设备技术到肺部的分子和细胞生物学。对于大多数传统药物而言，通过口服途径已实现了可接受的生物利用度和疗效。不幸的是，注射是生物治疗药物的常规给药方式，因此需要其他给药途径。许多关于吸入蛋白质、肽和DNA的临床前和临床研究已经完成，结果表明在肺部及全身均可实现疗效。尽管结果令人鼓舞，但吸入生物治疗药物的开发仍面临独特的问题，需要采用综合且合理的开发方法。水性蛋白质制剂通常对雾化不稳定，而粉末制剂在固态下的稳定性可能难以评估。现有设备的吸入器效率和重现性不尽人意，尽管技术改进带来了希望，但新设备尚未问世，且大多数生物治疗药物仍未进行试验。一旦这些分子进入肺部，它们还会受到多种高效清除机制的作用，这可能会显著降低其发挥作用的概率。尽管存在这些问题，但通过吸入方式进行测试的潜在药物数量仍在不断增加，这表明未来有望取得成功。本综述讨论了上述问题，并重点介绍了多种已作为吸入气雾剂给药的生物治疗药物。
