Pharmacokinetics study of arteether loaded solid lipid nanoparticles: An improved oral bioavailability in rats

• Published in: International journal of pharmaceutics 2014-05, Vol.466 (1-2), p.321-327
• Main Authors: Dwivedi, Pankaj, Khatik, Renuka, Khandelwal, Kiran, Taneja, Isha, Raju, Kanumuri Siva Rama, Wahajuddin, Paliwal, Sarvesh Kumar, Dwivedi, Anil Kumar, Mishra, Prabhat Ranjan
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Antimalarials - administration & dosage; Antimalarials - blood; Antimalarials - chemistry; Antimalarials - pharmacokinetics; Arteether; Artemisinins - administration & dosage; Artemisinins - blood; Artemisinins - chemistry; Artemisinins - pharmacokinetics; Biological Availability; Cell Line, Tumor; Cell Survival - drug effects; High pressure homogenizer; LC-MS; Lipids - chemistry; Male; Mice; Nanoparticles - administration & dosage; Nanoparticles - chemistry; Pharmacokinetics; Rats, Sprague-Dawley; SLN; Surface-Active Agents - chemistry
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2014.03.036

[Display omitted] Arteether (ART), an artemisinin derivative, is a life saving drug for multiple drug resistant malaria. It has a deliverance effect in Falciparum malaria and cerebral malaria. We have prepared solid lipid nanoparticles (SLN) by high pressure homogenization (HPH) technique. ART-loaded SLN (ART-SLN) has been produced reproducibly with homogeneous particle size. ART-SLN was characterized for their size measured by Zetasizer Nano-ZS, Malvern, UK and by high resolution transmission electron microscopy (HR-TEM) and which was found to be 100±11.2nm. The maximum percentage entrapment efficiency (%EE) determined with the high-performance liquid chromatography (HPLC) has been found to be 69±4.2% in ART-SLN-3. The release pattern from ART-SLN revealed that the release of ART is slow but time-dependent manner, which is desirable as it will help to protect the acid degradation of ART in stomach. The percentage cytotoxicity of blank SLN has been found within the acceptable range. The pharmacokinetics results indicated that ART-SLN-3 absorption has been significantly enhanced in comparison to ART in aqueous suspension and ART in ground nut oil (GNO) in rats. The % relative bioavailability (RB%) of ART-SLN to the ART in GNO and ART in aqueous suspension in rats was 169.99% and 7461%, respectively which was found to be significantly high in both the cases. From the results, it can be concluded that ART-SLN offers a new approach to improve the oral bioavailability of ART.