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Transferrin-conjugated Solid Lipid Nanoparticles for Enhanced Delivery of Quinine Dihydrochloride to the Brain

Transferrin-conjugated Solid Lipid Nanoparticles for Enhanced Delivery of Quinine Dihydrochloride to the Brain

Yashwant Gupta, Anekant Jain, Sanjay K Jain

J Pharm Pharmacol. 2007 Jul;59(7):935-40.

PMID: 17637187

Abstract:

Transferrin (Tf)-conjugated solid lipid nanoparticles (SLNs) were investigated for their ability to deliver quinine dihydrochloride to the brain, for the management of cerebral malaria. SLNs were prepared by an ethanol injection method using hydrogenated soya phosphatidyl choline (HSPC), triolein, cholesterol and distearylphosphatidylethanolamine (DSPE). Coupling of SLNs with Tf was achieved by incubation of Tf with quinine-loaded SLNs in the presence of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) hydrochloride in phosphate buffered saline (pH 7.4) as a cross-linker. SLNs were characterized for shape, particle size, polydispersity and percentage drug entrapment. The SLNs were 108-126 nm in size, and maximum drug entrapment was 38.4-42.7%. Average size increased on coupling with Tf but percentage drug entrapment was reduced. The in-vitro release profile was determined using a dialysis technique; non-conjugated SLNs released comparatively more drug than Tf-SLNs. Fluorescence studies revealed enhanced uptake of Tf-SLNs in brain tissue compared with unconjugated SLNs. In in-vivo performance studies, quinine plasma level and tissue distribution after intravenous administration of drug-loaded Tf-SLNs and unconjugated SLNs was compared with that of free drug. Intravenous administration of quinine dihydrochloride solution resulted in much higher concentrations of drug in the serum than with SLNs. Conjugation of SLNs with Tf significantly enhanced the brain uptake of quinine which was shown by the recovery of a higher percentage of the dose from the brain following administration of Tf-coupled SLNs compared with unconjugated SLNs or drug solution.

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