title: Artemisinin nanoformulation suitable for intravenous injection: Preparation, characterization and antimalarial activities.
abstract: More than 40 years after its discovery, artemisinin has become the most promising antimalarial agent. However, no intravenous formulation is available due to its poor aqueous solubility. Here, we report the preparation, characterization, and in vitro and in vivo biological evaluation of biodegradable albumin-bound artemisinin nanoparticles. The nanoparticles were prepared by a combination of a bottom-up and a top-down processes and characterized by different spectroscopic techniques. The preparation process was optimized to develop a nanoformulation with the smallest possible diameter and good homogeneity suitable for intravenous injection enabling direct contact of artemisinin with infected erythrocytes. Chemically and physically stable artemisinin nanoparticles were obtained with excellent entrapment efficiency. In in vitro experiments, the artemisinin nanoformulation was interestingly more effective than non-formulated artemisinin. In Plasmodiumm falciparum-infected 'humanized' mice, the nanoparticles proved to be highly effective with 96% parasitemia inhibition at 10mg/kg/day, prolonging mean survival time without recrudescence. This nanoparticulate albumin-bound system allows the intravenous administration of artemisinin for the first time without harsh organic solvents or cosolvents with 100% bioavailability.
authors.affiliation: Université de Toulouse, UPS, UMR 152 (PHARMA-DEV), F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Nehal
authors.initials: N
authors.lastname: Ibrahim
authors.affiliation: Université de Toulouse, UPS, UMR 152 (PHARMA-DEV), F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France. Electronic address: hanygamal85@hotmail.com.
authors.forename: Hany
authors.initials: H
authors.lastname: Ibrahim
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l'hôpital, F-75013 Paris, France; INSERM, U1135, CIMI-PARIS, 91 Bd de l'hôpital, F-75013 Paris, France; CNRS, ERL 8255, CIMI-PARIS, 91 Bd de l'hôpital, F-75013 Paris, France.
authors.forename: Alicia Moreno
authors.initials: AM
authors.lastname: Sabater
authors.affiliation: Sorbonne Universités, UPMC Univ. Paris 06, CR7, Centre d'Immunologie et des Maladies Infectieuses (CIMI-Paris), 91 Bd de l'hôpital, F-75013 Paris, France; INSERM, U1135, CIMI-PARIS, 91 Bd de l'hôpital, F-75013 Paris, France; CNRS, ERL 8255, CIMI-PARIS, 91 Bd de l'hôpital, F-75013 Paris, France; AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Service Parasitologie-Mycologie, Paris, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.affiliation: Université de Toulouse, UPS, UMR 152 (PHARMA-DEV), F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Valentin
authors.affiliation: Université de Toulouse, UPS, UMR 152 (PHARMA-DEV), F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Nepveu
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D037621:Artemisinins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D001682:Biological Availability; D004339:Drug Compounding; D007275:Injections, Intravenous; D016778:Malaria, Falciparum / Q000188:drug therapy* / Q000469:parasitology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D053758:Nanoparticles; D018512:Parasitemia / Q000188:drug therapy; D010316:Particle Size; D010963:Plasmodium falciparum; D012995:Solubility
chemical_list: D000962:Antimalarials; D037621:Artemisinins; C031327:artemisinin
keywords: Albumin; Artemisinin; High-pressure homogenization; Intravenous injection; Malaria; Nanoparticles