Influence of the introduction of a solubility enhancer on the formulation of lipidic nanoparticles with improved drug loading rates.
The objective of the present paper is to develop lipidic nanoparticles (NP) able to encapsulate drugs presenting limited solubility in both water and lipids, with high loading rates, and without using organic solvents. In this goal, a solubility enhancer, a macrogolglyceride (Labrasol), was incorporated in a formulation process based on a low-energy phase inversion temperature method. From electrical conductivity through the temperature scans, it appears that presence of Labrasol does not prevent the phase inversion, and it takes part in the microemulsion structuring, probably of bicontinuous type. After screening pseudo-ternary diagrams, the feasibility of NP was established. From results of a partial least square analysis, it appears that these NP present a core-shell structure where Labrasol is well encapsulated and contributes to the formation of the oily liquid core of the NP. The diameter of the NP, assessed by dynamic light scattering, remains kinetically stable. These NP, smaller than 200 nm, spherical in shape as attested by cryo-transmission electron micrographs, are able to encapsulate a tripentone, a new anticancer agent, with drug loading rates up to 6.5% (w/w). So highly drug-loaded lipidic nanocarriers were developed without using the slightest organic solvent trace, and making it easily possible dose adjustment.
Centre d'Etudes et de Recherche sur le Médicament de Normandie, Université de Caen Basse-Normandie, Caen Cedex, France. aurelie.malzert-freon@unicaen.fr
A
A
Malzert-Fréon
G
G
Saint-Lorant
D
D
Hennequin
P
P
Gauduchon
L
L
Poulain
S
S
Rault
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D004355:Drug Stability; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D005989:Glycerides; D016018:Least-Squares Analysis; D008055:Lipids / Q000737:chemistry; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009930:Organic Chemicals / Q000737:chemistry; D010316:Particle Size; D011763:Pyrrolizidine Alkaloids / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility; D013696:Temperature
C483893:3-(3-hydroxy-4-methoxyphenyl)-8H-thieno(2,3-b)pyrrolizin-8-one; D000970:Antineoplastic Agents; D004655:Emulsions; D005079:Excipients; D005989:Glycerides; D008055:Lipids; D009930:Organic Chemicals; D011763:Pyrrolizidine Alkaloids; C440220:Labrasol