title: Development of artemether-loaded nanostructured lipid carrier (NLC) formulation for topical application.
abstract: NLC topical formulation as an alternative to oral and parenteral (IM) delivery of artemether (ART), a poorly water-soluble drug was designed. A Phospholipon 85G-modified Gelucire 43/01 based NLC formulation containing 75% Transcutol was chosen from DSC studies and loaded with gradient concentration of ART (100-750 mg). ART-loaded NLCs were stable (-22 to -40 mV), polydispersed (0.4-0.7) with d90 size distribution range of 247-530 nm without microparticles up to one month of storage. The encapsulation efficiency (EE%) for ART in the NLC was concentration independent as 250 mg of ART loading achieved ∼61%. DSC confirmed molecular dispersion of ART due to low matrix crystallinity (0.028J/g). Ex vivo study showed detectable ART amounts after 20h which gradually increased over 48h achieving ∼26% cumulative amount permeated irrespective of the applied dose. This proves that ART permeates excised human epidermis, where the current formulation served as a reservoir to gradually control drug release over an extended period of time. Full thickness skin study therefore may confirm if this is a positive signal to hope for a topical delivery system of ART.
authors.affiliation: Drug Delivery Research Unit, Department of Pharmaceutics, University of Nigeria, Nsukka, Enugu State, Nigeria; Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany. Electronic address: petra.nnamani@unn.edu.ng.
authors.forename: Petra O
authors.initials: PO
authors.lastname: Nnamani
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Hansen
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany.
authors.forename: Maike
authors.initials: M
authors.lastname: Windbergs
authors.affiliation: Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Center for Infection Research, Saarland University, Saarbrücken, Germany; PharmBioTec GmbH, Saarbrücken, Germany; Department of Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbrücken, Germany.
authors.forename: Claus-Michael
authors.initials: CM
authors.lastname: Lehr
mesh_terms: D000287:Administration, Topical; D000962:Antimalarials / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000077549:Artemether; D037621:Artemisinins / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D005026:Ethylene Glycols / Q000737:chemistry; D005260:Female; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D008055:Lipids / Q000737:chemistry*; D046529:Microscopy, Electron, Transmission; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D010713:Phosphatidylcholines / Q000737:chemistry; D012867:Skin / Q000378:metabolism*; D012869:Skin Absorption / Q000187:drug effects; D012995:Solubility; D013499:Surface Properties; D014280:Triglycerides / Q000737:chemistry
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004337:Drug Carriers; D005026:Ethylene Glycols; D008055:Lipids; D010713:Phosphatidylcholines; D014280:Triglycerides; C507309:gelucire 43-01; C010111:carbitol; D000077549:Artemether
keywords: Artemether; Ex vivo skin permeation; Malaria; Nanostructured lipid carrier; Particle characterization; Topical formulation