{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:35:42Z","timestamp":1792089342020,"version":"4.4.0"},"reference-count":56,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,4,6]],"date-time":"2024-04-06T00:00:00Z","timestamp":1712361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Indian Council of Medical Research","award":["114\/2022-ECD-II"],"award-info":[{"award-number":["114\/2022-ECD-II"]}]},{"name":"Indian Council of Medical Research","award":["RGP. 1\/399\/44"],"award-info":[{"award-number":["RGP. 1\/399\/44"]}]},{"name":"King Khalid University","award":["114\/2022-ECD-II"],"award-info":[{"award-number":["114\/2022-ECD-II"]}]},{"name":"King Khalid University","award":["RGP. 1\/399\/44"],"award-info":[{"award-number":["RGP. 1\/399\/44"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Cerebral malaria (CM), a severe neurological pathology caused by Plasmodium falciparum infection, poses a significant global health threat and has a high mortality rate. Conventional therapeutics cannot cross the blood\u2013brain 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% (w\/w) precirol and 1.5% (w\/v) 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.<\/jats:p>","DOI":"10.3390\/ph17040466","type":"journal-article","created":{"date-parts":[[2024,4,8]],"date-time":"2024-04-08T10:11:55Z","timestamp":1712571115000},"page":"466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Pharmacokinetics and Pharmacodynamics of a Nanostructured Lipid Carrier Co-Encapsulating Artemether and miRNA for Mitigating Cerebral Malaria"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1409-5998","authenticated-orcid":false,"given":"Veera Venkata Nishanth","family":"Goli","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru 570015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-0041","authenticated-orcid":false,"given":"Spandana","family":"Tatineni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru 570015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4643-0922","authenticated-orcid":false,"given":"Umme","family":"Hani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3555-4268","authenticated-orcid":false,"given":"Mohammed","family":"Ghazwani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2334-2332","authenticated-orcid":false,"given":"Sirajunisa","family":"Talath","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, RAK College of Pharmacy, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9100-2508","authenticated-orcid":false,"given":"Sathvik Belagodu","family":"Sridhar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy & Pharmacology, RAK College of Pharmaceutical Sciences, RAK Medical and Health Sciences University, Ras Al Khaimah 11172, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8368-9047","authenticated-orcid":false,"given":"Yahya","family":"Alhamhoom","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5783-9363","authenticated-orcid":false,"given":"Farhat","family":"Fatima","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-0817","authenticated-orcid":false,"given":"Riyaz Ali M.","family":"Osmani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru 570015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0365-5080","authenticated-orcid":false,"given":"Umamaheshwari","family":"Shivaswamy","sequence":"additional","affiliation":[{"name":"Department of Microbiology, JSS Academy of Higher Education and Research, Mysuru 570015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vichitra","family":"Chandrasekaran","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru 570015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7590-5160","authenticated-orcid":false,"given":"Bannimath","family":"Gurupadayya","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, JSS College of Pharmacy, JSS Academy of Higher Education and Research, Shivarathreeshwara Nagara, Mysuru 570015, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Song, X., Wei, W., Cheng, W., Zhu, H., Wang, W., Dong, H., and Li, J. 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