Goli Veera Venkata Nishanth, Tatineni Spandana, Hani Umme, Ghazwani Mohammed, Talath Sirajunisa, Sridhar Sathvik Belagodu, Alhamhoom Yahya, Fatima Farhat, Osmani Riyaz Ali M, Shivaswamy Umamaheshwari, Chandrasekaran Vichitra, Gurupadayya Bannimath
Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru 570015, India.
Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.
Pharmaceuticals (Basel). 2024 Apr 6;17(4):466. doi: 10.3390/ph17040466.
Cerebral malaria (CM), a severe neurological pathology caused by infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood-brain barrier (BBB) efficiently. Therefore, finding effective treatments remains challenging. The novelty of the treatment proposed in this study lies in the feasibility of intranasal (IN) delivery of the nanostructured lipid carrier system (NLC) combining microRNA (miRNA) and artemether (ARM) to enhance bioavailability and brain targeting. The rational use of NLCs and RNA-targeted therapeutics could revolutionize the treatment strategies for CM management. This study can potentially address the challenges in treating CM, allowing drugs to pass through the BBB. The NLC formulation was developed by a hot-melt homogenization process utilizing 3% (/) precirol and 1.5% (/) labrasol, resulting in particles with a size of 94.39 nm. This indicates an effective delivery to the brain via IN administration. The results further suggest the effective intracellular delivery of encapsulated miRNAs in the NLCs. Investigations with an experimental cerebral malaria mouse model showed a reduction in parasitaemia, preservation of BBB integrity, and reduced cerebral haemorrhages with the ARM+ miRNA-NLC treatment. Additionally, molecular discoveries revealed that nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) and Interleukin-6 (IL-6) levels were reduced in the treated groups in comparison to the CM group. These results support the use of nanocarriers for IN administration, offering a viable method for mitigating CM through the increased bioavailability of therapeutics. Our findings have far-reaching implications for future research and personalized therapy.
脑型疟疾（CM）是一种由感染引起的严重神经病理学疾病，对全球健康构成重大威胁，死亡率很高。传统疗法无法有效穿过血脑屏障（BBB）。因此，寻找有效的治疗方法仍然具有挑战性。本研究提出的治疗方法的新颖之处在于，通过鼻内（IN）递送结合微小RNA（miRNA）和蒿甲醚（ARM）的纳米结构脂质载体系统（NLC）来提高生物利用度和脑靶向性具有可行性。合理使用NLC和RNA靶向疗法可能会彻底改变CM治疗策略。本研究有可能解决CM治疗中的挑战，使药物能够穿过血脑屏障。NLC制剂是通过热熔均质工艺开发的，使用3%（/）的Precirol和1.5%（/）的Labrasol，得到的颗粒大小为94.39nm。这表明通过鼻内给药可有效递送至大脑。结果进一步表明，NLC中封装的miRNA可有效进行细胞内递送。对实验性脑型疟疾小鼠模型的研究表明，ARM+miRNA-NLC治疗可降低寄生虫血症，保持血脑屏障完整性，并减少脑出血。此外，分子研究发现，与CM组相比，治疗组中烟酰胺腺嘌呤二核苷酸磷酸氧化酶2（NOX2）和白细胞介素-6（IL-6）水平降低。这些结果支持使用纳米载体进行鼻内给药，为通过提高治疗药物的生物利用度来减轻CM提供了一种可行的方法。我们的发现对未来的研究和个性化治疗具有深远意义。
