Dual drug delivery of cyclodextrin cross-linked artemether and lumefantrine nanosponges for synergistic action using 23 full factorial designs

To improve the physicochemical properties of artemether and lumefantrine, cyclodextrin-based carriers like nanoparticle, microcomplex, nanosponges, etc. play a significant role in the development of dosage forms. The current study focused on the formulation of cyclodextrin-based artemether and lumefantrine-loaded nanosponges to improve the solubility and stability of actives with controlled-release profile. Nanosponges were synthesized using solvent evaporation method and statistically optimized using 2(3) full factorial designs. Nanosponges showed mean particle size of 316.4 +/- 8.5 nm and % entrapment efficiencies of 70.6 +/- 1.5 % and 88.3 +/- 2.5 % for artemether and lumefantrine, respectively. SEM and TEM analysis revealed the spherical structure of nanosponges with porous surfaces. In-vitro release study of nanosponges showed controlled-release of actives fill 24 h. In-vitro antimalarial study showed significant action of nanosponges towards RKL-9 strains in comparison to MRC-2 strains. The pharmacokinetic study of nanosponges showed that the parameters (Cmax and AUC) were under the acceptable limits with increased mean residence time of actives in the blood circulation. The data of stability study demonstrated that nanosponges were stable at 40 degrees C for 3 months. Thus, hypercross-linked cyclodextrin nanosponges advance as a novel nanocarrier system for controlled-release formulations of BCS class II and IV drugs.