Development and evaluation of anti-malarial bio-conjugates: artesunate-loaded nanoerythrosomes
- 246 Downloads
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.
KeywordsAnti-malarial Artesunate Cellular carrier Erythrocytes Nanoerythrocytes Targeting
The authors are thankful to Prof. Vandana B Patrawala, Department of Pharmaceutical Sciences and Technology, Institute of Chemical Technology, and lab staff for their invaluable help in handling and operating of the instruments in their laboratory for this research work.
Conflict of interest
The authors declare that there is no conflict of interest.
- 1.Anvikar AR, Arora U, Sonal GS, Mishra N, Shahi B, Savargaonkar D, et al. Anti malarial drug policy in India: Past, present and future. Ind J Med Res. 2014;139(2):205–15.Google Scholar
- 16.Gaudreault RC, Gicquaud C, Poyet P. Nanoerythrosome as bioactive agent carrier. 1997;US patent 5653999Google Scholar
- 18.Jain S, Jain NK. Engineered erythrocytes as a drug delivery system. Ind J Pharm Sci. 1997;59(6):275–81.Google Scholar
- 22.Bellemare F, Gaudreault R. Polyethyleneglycol conjugated nanoerythrosomes, method of making same and use thereof. 1998;Patent WO1998011919 A2.Google Scholar
- 23.Agnihotri J, Jain NK. Biodegradable long circulating cellular carrier for antimalarial drug pyrimethamine, Artificial Cells, Nanomedicine, and Biotechnology. 2013;41(5):309–14.Google Scholar
- 26.Merkus HG. Particle Size, Size Distribution and Shape. In: Particle Size Measurements: Fundamentals, Practice, Quality. Netherlands: Springer; 2009. p. 13 − 42Google Scholar
- 27.Particle size, Particle size distributions from sub-nanometer to millimetres. www.malvern.com. Available at: http://www.malvern.com/en/products/measurement-type/particle-size/default.aspx. Accessed on: 12th Dec. 2014.
- 28.Patravale V, Dandekar P, Jain R. Nanoparticulate Drug Delivery: Perspectives on the Transition from Laboratory to Market. In: Nanoparticulate Drug Delivery. 1st edition. UK: Woodhead Publishing Ltd; 2012. p. 65–7.Google Scholar
- 29.Liberman HA, Martin MR, Banker GS. Pharmaceutical Dosage forms Dispersed systems. Vol 2. New York: Marcel Dekker; 1996. p. 285.Google Scholar
- 30.Avis KE, Lachman L. Theory and Practice of Industrial Pharmacy. 3rd ed. Bombay: Varghese publishing; 1976. p. 654.Google Scholar
- 31.Nash RA. Formulation of pharmaceutical suspension. Part I. Drug and Cosmetic Industry. 1965;97:843.Google Scholar