The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update.
The expanding role of aerosols in systemic drug delivery, gene therapy and vaccination: an update.
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DOI：
10.1186/2213-0802-2-3
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Laube BL
中科院分区：
文献类型：
--
作者：
Laube BL
直到20世纪90年代末，气雾剂治疗包括β 2-肾上腺素能激动剂、抗胆碱能药物、类固醇和非类固醇药物、粘液溶解剂和抗生素，用于治疗哮喘、COPD和囊性纤维化患者。从那时起，吸入疗法已经成熟，包括药物：（1）旨在治疗肺外疾病，其目标是体循环（2）递送导致基因构建体或蛋白质编码序列在细胞群体中永久表达的核酸（基因治疗）;和（3）提供针对疾病的无针免疫（雾化接种）。在这些先进应用的发展过程中，还需要开发新的设备，以提高给药效率并减少输送过程中的损失。本次审查将介绍这些新应用程序及其设备的成功更新。雾化系统给药的早期承诺及其未来成功的前景将得到强调。此外，雾化基因治疗的挑战和需要适当的基因载体将进行讨论。最后，将介绍雾化疫苗接种的发展进展。未来气雾剂治疗作用的持续扩展将取决于：（1）提高全身递送药物的生物利用度;（2）开发能够有效穿透粘液屏障和细胞膜、导航细胞质并将DNA物质有效转移到细胞核的基因治疗载体;（3）改善基因载体和疫苗向婴儿的递送;和（4）开发对急性和慢性给药安全的制剂。
Until the late 1990s, aerosol therapy consisted of beta2-adrenergic agonists, anti-cholinergics, steroidal and non-steroidal agents, mucolytics and antibiotics that were used to treat patients with asthma, COPD and cystic fibrosis. Since then, inhalation therapy has matured to include drugs that: (1) are designed to treat diseases outside the lung and whose target is the systemic circulation (systemic drug delivery); (2) deliver nucleic acids that lead to permanent expression of a gene construct, or protein coding sequence, in a population of cells (gene therapy); and (3) provide needle-free immunization against disease (aerosolized vaccination). During the evolution of these advanced applications, it was also necessary to develop new devices that provided increased dosing efficiency and less loss during delivery. This review will present an update on the success of each of these new applications and their devices. The early promise of aerosolized systemic drug delivery and its outlook for future success will be highlighted. In addition, the challenges to aerosolized gene therapy and the need for appropriate gene vectors will be discussed. Finally, progress in the development of aerosolized vaccination will be presented. The continued expansion of the role of aerosol therapy in the future will depend on: (1) improving the bioavailability of systemically delivered drugs; (2) developing gene therapy vectors that can efficiently penetrate the mucus barrier and cell membrane, navigate the cell cytoplasm and efficiently transfer DNA material to the cell nucleus; (3) improving delivery of gene vectors and vaccines to infants; and (4) developing formulations that are safe for acute and chronic administrations.