Self-assembled biotransesterified cyclodextrins as Artemisinin nanocarriers - I: formulation, lyoavailability and in vitro antimalarial activity assessment.
We recently reported a one-step transesterification of cyclodextrins (CDs) by vinyl-acyl fatty esters catalyzed by thermolysin. By using the solvent displacement method and depending on the experimental conditions, the CD derivatives grafted with decanoic alkyl chains (CD-C(10)) yielded either nanosphere or nanoreservoir-type systems with a size ranging from 70 to 220 nm. Both types of nanostructures were able to associate artemisinin (ART), a well-known antimalarial lipophilic drug. The formulation parameters were optimized to reach stable and high ART dosage corresponding to drug levels of 0.3 and 1.6 mg mL(-1) in the colloidal suspension, for the spherical and reservoir-type nanosystems, respectively. PEG surface-decorated nanoparticles were also prepared by co-nanoprecipitation of PEG fatty acid esters and CD-C(10) molecules. The integration of the PEGylated amphiphiles within the CD-C(10) nanostructures did not influence the ART lyoavailability. Both types of ART-loaded nanosystems showed a sustained in vitro release profile over 96 (nanoreservoirs) and 240 h (nanospheres). Finally, the in vitro antimalarial activity was evaluated using the lactate dehydrogenase assay. ART-containing colloidal suspensions inhibited the growth of cultured Plasmodium falciparum, both multi-resistant K1 and susceptible 3D7 strains with IC(50) values (2.8 and 7.0 ng mL(-1)) close to those of reference ART solution. These colloidal nanosystems based on CD derivatives and containing ART may provide a promising alternative formulation for injectable use of ART.
DPM, UMR CNRS 5063, ICMG FR 2607, Faculty of Pharmacy, University of Grenoble, France.
Josias B G
JB
Yaméogo
Annabelle
A
Gèze
Luc
L
Choisnard
Jean-Luc
JL
Putaux
Adama
A
Gansané
Sodiomon B
SB
Sirima
Rasmané
R
Semdé
Denis
D
Wouessidjewe
D000962:Antimalarials / Q000737:chemistry* / Q000494:pharmacology*; D037621:Artemisinins / Q000737:chemistry* / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003102:Colloids / Q000737:chemistry / Q000494:pharmacology; D003505:Cyclodextrins / Q000737:chemistry*; D004337:Drug Carriers / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry; D010316:Particle Size; D010963:Plasmodium falciparum / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry / Q000494:pharmacology; D013535:Suspensions / Q000737:chemistry / Q000494:pharmacology
D000962:Antimalarials; D037621:Artemisinins; D003102:Colloids; D003505:Cyclodextrins; D004337:Drug Carriers; D012997:Solvents; D013501:Surface-Active Agents; D013535:Suspensions; D011092:Polyethylene Glycols; C031327:artemisinin