Shah Pranav, Lalan Manisha, Barve Kalyani
Maliba Pharmacy College, Uka Tarsadia University, Surat, India.
Shobhaben Pratapbhai Patel School of Pharmacy and Technology Management, SVKM's Narsee Monjee Institute of Management Studies, Mumbai, Maharashtra, India.
Front Pharmacol. 2022 Aug 30;13:974666. doi: 10.3389/fphar.2022.974666. eCollection 2022.
The etiologies of several cardiovascular, inflammatory, neurological, hereditary disorders, cancer, and infectious diseases have implicated changes in the genetic set up or genetic mutations as the root cause. Nucleic acid based therapeutics (NBTs) is a new class of biologics that are known to regulate gene expression at the transcriptional and post-transcriptional level. The NBTs include oligonucleotides, nucleosides, antisense RNA, small interfering RNAs, micro RNA etc. In recent times, this new category of biologics has found enormous potential in the management of cardiovascular, inflammatory, neurological disorders, cancer, infectious diseases and organ transplantation. However, the delivery of NBTs is highly challenging in terms of target specificity (intracellular delivery), mononuclear phagocyte system uptake, stability and biodistribution. Additionally, management of the above mentioned disorders require regular and intrusive therapy making non-invasive routes preferable in comparison to invasive routes like parenteral. The nasal route is garnering focus in delivery of NBTs to the brain in the management of several CNS disorders due to the associated merits such as non-invasiveness, possibility of chronic delivery, improved patient compliance, avoidance of hepatic and gastrointestinal metabolism as well as ability to bypass the BBB. Hence in recent times, this route has been sought by the reserachers as an alternative to parenteral therapy for the delivery of several NBTs. This review shall focus on an array of NBTs delivered through nasal route, their challenges, applications and opportunities. The novel delivery systems for incorporating NBTs; their targeting strategies shall be critically reviewed. The challenges towards regulatory approvals and commercialization shall also be discussed at large. Comparison of learnings derived from the success and barriers in nasal delivery of NBTs will help in identification of futuristic opportunities for their translation from bench to bedside.
多种心血管疾病、炎症性疾病、神经系统疾病、遗传性疾病、癌症和传染病的病因都表明，基因组成的改变或基因突变是根本原因。基于核酸的疗法（NBTs）是一类新型生物制剂，已知可在转录和转录后水平调节基因表达。NBTs包括寡核苷酸、核苷、反义RNA、小干扰RNA、微小RNA等。近年来，这类新型生物制剂在心血管疾病、炎症性疾病、神经系统疾病、癌症、传染病和器官移植的治疗中发现了巨大潜力。然而，NBTs的递送在靶标特异性（细胞内递送）、单核吞噬细胞系统摄取、稳定性和生物分布方面极具挑战性。此外，上述疾病的治疗需要定期且侵入性的治疗，与非肠道等侵入性途径相比，非侵入性途径更可取。由于具有非侵入性、慢性递送的可能性、患者依从性提高、避免肝脏和胃肠道代谢以及绕过血脑屏障的能力等优点，鼻腔途径在治疗多种中枢神经系统疾病时将NBTs递送至大脑方面正受到关注。因此，近年来，研究人员寻求将该途径作为几种NBTs非肠道治疗的替代方法。本综述将聚焦于通过鼻腔途径递送的一系列NBTs、它们面临的挑战、应用和机遇。将对用于纳入NBTs的新型递送系统及其靶向策略进行严格审查。还将广泛讨论监管批准和商业化面临的挑战。比较从NBTs鼻腔递送的成功经验和障碍中获得的经验教训，将有助于确定将其从实验室转化为临床应用的未来机遇。
