Compatibilized Biopolymer-based Core-shell Nanoparticles: A New Frontier in Malaria Combo-therapy

Purpose Nano-sized biopolymer-based strategies such as spatio-temporal co-delivery of bioactives could be employed to overcome low bioavailability of antimalarial drugs delivered by conventional dosage forms in malaria combo-therapy. This work reports on the development of core-shell nanocarrier using a biocomposite containing Prosopis africana gum (PG) and microcrystalline cellulose (MCC) for spatio-temporal delivery of artemether and lumefantrine (AL) to enhance oral malaria treatment. Methods The biocomposite was prepared by pH-dependent temperature-controlled coacervation and characterized by differential scanning calorimetry, thermogravimetric measurements, and time-domain nuclear magnetic resonance relaxometry. Nanocarrier containing AL was produced using the combination of high-shear homogenization and nanoprecipitation techniques, characterized regarding physicochemical performance, in-vitro dissolution and stability. In-vivo studies were performed in mice infected with Plasmodium berghei parasite. Results Biocomposite containing 1:1 ratio of PG:MCC gave the best physicochemical properties. The nanoparticles were spherical with a smooth surface, gave encapsulation efficiency of 81.23 +/- 1.54% and 57.15 +/- 0.86% for artemether and lumefantrine, respectively, and exhibited an average size of 208.29 +/- 0.94 nm, a low polydispersity index value (0.141 +/- 0.02) indicating a narrow size distribution and a positive charge of 34.51 +/- 1.05 mV. The nanoparticles provided a quick release for artemether and a slow release for lumefantrine within 8 h, indicating the suitability for spatio-temporal drug delivery in malaria combo-therapy. Optimized AL-loaded nanoformulation was stable, histopathologically safe on major organs implicated in malaria and exhibited greater antimalarial activity than marketed AL. Conclusion These results postulate the developed core-shell nanocarrier as versatile drug co-delivery nanoplatform and potential alternative approach to improve the pharmacodynamics of AL combo-therapies in malaria treatment.