Abstract
Protease inhibitors such as lopinavir have negligible permeability to the CNS due to blood-brain and blood-cerebrospinal fluid interfaces. An attempt has been made to develop solid lipid nanoparticles to increase the availability of lopinavir in the CNS. Solid lipid nanoparticle formulations exhibited a Cmax and T(max) of 632.86 +/- 81.61 ng/ml and 25 +/- 7.75 min, respectively, with a significant increase in bioavailability in a rat model compared with a free-drug suspension. An appreciable increase in cerebrospinal fluid concentration was detected with solid lipid nanoparticle formulations. Compritol-based solid lipid nanoparticles with a poloxamer coating can be effectively absorbed through the lymphatic system, prolong the circulation of drug in blood by acting as a reservoir and can effectively target the drug to the CNS due to the combined effect of lipophilicity and surface charge. The high biocompatibility, biodegradability and nontoxicity of compritol make the compritol-based solid lipid nanoparticles an excellent carrier for enhanced CNS delivery of lopinavir.
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