Lipid nanoparticles with a solid matrix (SLN, NLC, LDC) for oral drug delivery.

Solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), and lipid-drug conjugates (LDC), commonly produced by high-pressure homogenization, are interesting vectors for oral delivery of lipophilic and, to a certain extent, hydrophilic substances. Their production can be done without the use of organic solvents. Techniques to make them a physically stable delivery system have been developed. Scaling up of the production process from lab-size to large-scale dimensions using high-pressure homogenization can be easily achieved by using a different type of homogenizer. The machines used for large-scale production often yield an even better product quality than the lab-scale types. This review article covers the methods of production, characterization, mechanisms of oral bioavailability enhancement, scale-up, final oral dosage forms, and regulatory aspects of lipid nanoparticles for oral drug delivery. It focuses mainly on high-pressure homogenization production methods.

Comparison of nanosuspensions and hydroxypropyl-beta-cyclodextrin complex of melarsoprol: pharmacokinetics and tissue distribution in mice.

The aim of this work was to develop and compare two formulations of melarsoprol (nanosuspension and hydroxypropyl-beta-cyclodextrin inclusion complex). The arsenic concentrations in the organs have been assessed on a mouse model. Since this organoarsenical drug has been proposed for the treatment of cerebral trypanosomiasis and refractory leukaemias, special emphasis has been put on the bone marrow and on the brain. The organic solution of melarsoprol (Mel B, 0.039mmol/kg), injected intravenously as control formulation, was found to concentrate significantly in the bone marrow (C(max)=1.64mmol/g), though, not surprisingly, the brain concentration was quite high (C(max)=0. 093mmol/g) and the LD(50) was 0.12mmol/kg. The hydroxypropyl-beta-cyclodextrin inclusion complex was found to concentrate much more in the brain (C(max)=0.25mmol/g) leading to a higher acute toxicity (i.e., lower LD(50); 0.056mmol/kg). Nevertheless, even if the encephalopathy risk has to be taken in to account, this could be considered as a positive point for the treatment of the cerebral trypanosomiasis, which is the main indication for this drug. On the contrary, the use of nanosuspensions allowed us to reduce the cerebral concentration (C(max)=0.02micromol/g) and the acute toxicity (LD(50)=0.25mmol/kg). Moreover, nanosuspensions, especially those prepared with polxamer 407, preserved a good in vitro antileukemic activity (IC(50)=3.34+/-0.33 after 48h on K562) with high bone marrow concentrations (C(max)=1.85micromol/g). As a consequence this formulation could be proposed for the treatment of refractory leukaemias.