title: 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.
authors.affiliation: H. K College of Pharmacy, Jogeshwari West, Mumbai, MH, India, arnapadii@yahoo.com.
authors.forename: Jaya
authors.initials: J
authors.lastname: Agnihotri
authors.forename: Shubhini
authors.initials: S
authors.lastname: Saraf
authors.forename: Sobhna
authors.initials: S
authors.lastname: Singh
authors.forename: Papiya
authors.initials: P
authors.lastname: Bigoniya
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D037621:Artemisinins / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000077332:Artesunate; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D016503:Drug Delivery Systems; D065546:Drug Liberation; D004912:Erythrocytes; D005260:Female; D008297:Male; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry; D051381:Rats
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D003692:Delayed-Action Preparations; D000077332:Artesunate