Zein and Fish Gelatin as Stabilizers for Lumefantrine and Delamanid Nanoparticles

Abstract

Lumefantrine, an antimalarial drug, and Delamanid, an antituberculosis drug, have low bioavailability due to their hydrophobic characters. Therefore, higher doses of these drugs are needed to achieve effective plasma concentrations. Finding a low cost nanoparticle formulation and a way to improve the bioavailability and the long term stability of these drugs is of interest so that they can be delivered to and stored in underdeveloped countries under sub-optimal conditions and be more effective at lower doses. In this work, the flash nanoprecipitation process was used to prepare Lumefantrine and Delamanid nanoparticles using either zein and casein or fish gelatin/high molecular weight (HMW) fish gelatin as outer layers. Either spray drying or lyophilization was applied and the release kinetics and stability of the nanoparticles were tested. Stability after spray drying was shown in the formulation involving Lumefantrine and zein as the outer layer. It was observed that the lyophilized nanoparticles in the Lumefantrine formulation involving fish gelatin as the outer layer released more quickly in the FaSSGF, FaSSIF, and FeSSIF than the lyophilized nanoparticles in the formulation involving HMW fish gelatin as the outer layer as well as the spray dried samples with fish gelatin. The formulation with Delamanid and zein as the outer coating was shown to be stable for three hours. However, no stable formulation involving Delamanid with fish gelatin/HMW fish gelatin outer layer was found.