Sinefungin-PLGA nanoparticles: drug loading, characterization, in vitro drug release and in vivo studies.

Cryptosporidiosis, the leading cause of endemic and epidemic diarrhoeal disease worldwide is due to Cryptosporidium parvum, a spore-forming protozoan. Anticryptosporidial pharmacological and/or immunological agents were initially tested in immunodeficient models of cryptosporidiosis, and sinefungin exhibited a significant dose dependent curative and preventive activity. Shedding relapses observed after discontinuation of sinefungin therapy lead to identify the bile ducts as a protected reservoir that may sustain chronic infection. The MIC50 of the sinefungin observed in vitro studies is 14.5 microg/ml. It is a hydrophilic drug lowly absorbed when orally administered and nephrotoxic after IV injection. To avoid this toxic effect, Neal's team prepared sinefungin loaded microspheres and proved that encapsulated sinefungin was 10 times more effective than free sinefungin. This optimistic result led us to study the nanoparticles as drug carrier for sinefungin. In this study, we prepared optimal sinefungin loaded PLGA nanoparticles. Physico-chemical characterization, in vitro drug release and in vivo studies were assessed. Negative surface-charged (-56.1 mV) sinefungin loaded PLGA nanoparticles were prepared with a homogenous size of 200 nm. Optimal formulation led to a drug content of 9.18% w/w (4.59 mg) and a drug entrapment of 15.16%. Dilution technique was used to study the release of sinefungin in vitro. 93.03% of sinefungin were released from dilution 1:5 to 1:20. This burst effect could probably due to the adsorption of the drug on the surface of the nanoparticles. A second step with a lower release was observed from dilution 1:20 to 1:100 which may correspond to the diffusion out of the drug solution from the nanoparticles into the bulk release medium. Investigations in rats showed that only 1.23 mg of sinefungin loaded in PLGA nanoparticles led to a decrease of sinefungin in the urine (0.23 mg vs. 4.27 mg for IV administration of free sinefungin) and to an increase of sinefungin concentration in the bile (6.63 microg/ml vs. 3.89 microg/ml for IV administration of free sinefungin). But the biliary concentration of encapsulated sinefungin (6.63 microg/ml) is still nearly 2 times lower than the MIC50.

Investigations on topically applied vitamin A loaded amphiphilic cyclodextrin nanocapsules.

A new cholesteryl-cyclodextrin derivative, obtained by grafting a single cholesterol on a cyclodextrin, was proved suitable for the manufacture of nanocapsules. The chemical structure of Chol-betaCD-Ac was assessed using high resolution 1H-NMR. These nanocapsules were loaded with a lipophilic drug, i.e., vitamin A propionate (PRVA) which is a highly unstable and poorly water soluble molecule with a real interest in therapeutic. The oily nature of vitamin A propionate leads to the formation of nanocapsules with a reproductible size distribution and a long term stability. The colloidal suspension can be used to form a gel which allow to achieve penetration in the skin of the PRVA encapsulated.