Development and evaluation of anti-malarial bio-conjugates: artesunate-loaded nanoerythrosomes

Abstract

Biodegradable cellular carrier has desired properties for achieving effective long-term controlled release of drugs having short half life. To reduce the undesired effects of drug, advanced drug delivery systems are needed which are based on specific cell targeting module. Artesunate (ART) conjugation on nanoerythrosomes (NE) can have controlled delivery to avoid drug leakage, increase the stability, and reduce cost and toxicities. In this study nanosized lipoprotein membrane vesicles bearing ART were prepared by extrusion method. Developed ART-NE conjugate formulations were optimized on the basis of vesicle morphology, size and size distribution, polydispersity index, integrity of membrane, loaded drug concentration, drug leakage, effect of temperature and viscosity, syringeability, in vitro release profile and in vivo plasma concentration estimation studies. Fourier transform infrared (FTIR) spectroscopy reveals that lipid chain order of RBCs are insignificantly affected in moderate conditions after ART loading. The formulated ART-NE carrier revealed non aggregated, uniformly sized particles with smooth surfaces. The maximum drug loading was found to be 25.20 ± 1.3 μg/ml. ART-NE formulation was best fit for zero order kinetics and was found to be capable of controlled release of drug for 8 hrs. ART-NE formulation showed good redispersibility with desirable properties for parenteral administration. Formulation was stable when subjected to stress by centrifugal force of 7500 rpm and could bear turbulence shock of 15 passes from hypodermic needle of size 23 gauges. The ART-NE formulation administered intravenously showed higher plasma concentration compared to free drug signifying not only controlled release but higher rate of in vivo release. The developed formulation exhibited zero order release profile as per kinetic study analysis suggesting the suitability of carrier for the sustained and targeted delivery of ART. The developed ART-NE drug delivery system offers improved pharmacokinetic profile with assurance of increased therapeutic efficacy.

Red blood cells as an efficient in vitro model for evaluating the efficacy of metallic nanoparticles

“…In vitro studies prove that the nanoerythrosomes are successful prototype to carry loaded cytotoxic agents as anticancer therapy (Désilets et al 2001). It is also reported that nanoerythrosomes, hybrid RBCs was the successful in delivering anti-malarial agents as compared to free drug in the rat model (Agnihotri et al 2015).…”

Nanoparticle Delivery of Artesunate Enhances the Anti-tumor Efficiency by Activating Mitochondria-Mediated Cell Apoptosis

“…To enhance the anti-tumor effects of Ats, many new techniques were attempted to increase the drug’s distribution in tumor cells or to improve the targeted delivery of drugs into cell organelles to induce cell death [21–23]. Nanoparticles (NPs) as a key tool in targeted cancer treatment have been widely investigated, and they have shown promising potential.…”

Red blood cells: Supercarriers for drugs, biologicals, and nanoparticles and inspiration for advanced delivery systems

“…Notwithstanding, this DDS apparently had not been pursued to the level of systematic studies in vivo , perhaps due to very rapid clearance from blood, as this formulation lost biocompatibility [181]. In one recent study, nanoerythrosomes filled with anti-malarial agents were cleared in rats within a few hours (although slightly slower than free drug) [182]. …”