MANNOSYLATED MULTIWALLED CARBON NANOTUBES ASSISTED ARTESUNATE DELIVERY FOR CEREBRAL MALARIA
MULTIWALLED CARBON NANOTUBES ASSISTED ARTESUNATE DELIVERY
Keywords:Carbon Nanotubes, Cerebral malaria, Artesunate
Objective: The present investigation focused on the novel approach using artesunate (AS) loaded mannosylated conjugated multi-walled carbon nanotubes (M-MWCNTs) for site-specific delivery to the brain in the treatment of cerebral malaria (CM).
Methods: The raw MWCNTs were purified by selective oxidation method and then exposed to sequential chemical functionalization according to the following steps: carboxylation, acylation, amine modification and finally, D-mannose conjugation. The AS was loaded via the equilibrium dialysis method in the molar ratio 1:3 of various functionalized sonicated MWCNTs. The functionalized MWCNTs were characterized for elemental analysis, FTIR, TEM, zeta potential and percentage drug entrapment efficiency. The in vitro drug release study was performed on AS conjugated purified MWCNTs (AS-P-MWCNT) and AS conjugated M-MWCNTs. Bio-distribution study was performed on albino rat for quantitative measurement of AS in different organs and blood.
Results: The TEM images of M-MWCNTs indicated their open tubular nature and AS-M-MWCNTs suggests the entrapment of AS. The percent drug entrapment of AS-M-MWCNT was found to be 80.29±3.4 %. In vitro AS release from AS-M-MWCNTs was found in a controlled manner at pH 7.4. The bio-distribution studies clearly indicate the superiority of the AS-M-MWCNTs, as compared to the plain drug towards increasing the accumulation of AS in brain.
Conclusion: The results suggest that AS-M-MWCNTs could be employed as an efficient nano-carrier for antimalarial therapy in cerebral malaria.
Simner P. Medical parasitology taxonomy update. J Clin Microbiol 2017;55:43-7.
Golenser J, McQuillan J, Hee L, Mitchell AJ, Hunt NH. Conventional and experimental treatment of cerebral malaria. Int J Parasitol 2006;36:583-93.
Gay F, Zougbede S, N'Dilimabaka N, Rebollo A, Mazier D, Moreno A. Cerebral malaria: what is known and what is on research. Rev Neurol (Paris) 2012;168:239-56.
Iijima S. Helical microtubules of graphitic carbon. Nature 1991. p. 56-8.
Davis JJ, Coleman KS, Azamian BR, Bagshaw CB, Green ML. Chemical and biochemical sensing with modified single walled carbon nanotubes. Chem Eur J 2003;9:3732-9.
Martin CR, Kohli P. The emerging field of nanotube biotechnology. Nat Rev Drug Discovery 2003;2:29-37.
Sajid MI, Jamshaid U, Jamshaid T, Zafar N, Fessi H, Elaissari A. Carbon nanotubes from synthesis to in vivo biomedical applications. Int J Pharm 2016;501:278-99.
Shen J, Huang W, Wu L, Hu Y, Ye M. Thermo-physical properties of epoxy nanocomposites reinforced with amino-functionalized multi-walled carbon nanotubes. Composites Part A: Appl Sci Manufacturing 2007;38:1331-6.
Lodhi N, Mehra NK, Jain NK. Development and characterization of dexamethasone mesylate anchored on multi-walled carbon nanotubes. J Drug Target 2013;21:67-76.
Pruthi J, Mehra NK, Jain NK. Macrophages targeting of amphotericin B through mannosylated multiwalled carbon nanotubes. J Drug Target 2012;20:593-604.
Gong B, Ikematsu A, Waki K. Impacts of structure defects and carboxyl and carbonyl functional groups on the work function of multiwalled carbon nanotubes. Carbon 2017;114:526-32.
Jain AK, Dubey V, Mehra NK, Lodhi N, Nahar M, Mishra DK, et al. Carbohydrate-conjugated multiwalled carbon nanotubes: development and characterization. Nanomedicine 2009;5:432-42.
Jain AK, Kumar Mehra N, Lodhi N, Dubey V, Mishra DK, Jain PK, et al. Carbon nanotubes and their toxicity. Nanotoxicology 2007;1:167-97.
Nahar M, Jain NK. Preparation, characterization and evaluation of targeting potential of amphotericin B-loaded engineered PLGA nanoparticles. Pharm Res 2009;26:2588-98.
Ma PC, Kim JK, Tang BZ. Functionalization of carbon nanotubes using a silane coupling agent. Carbon 2006;44:3232-8.
Wu W, Wieckowski S, Pastorin G, Benincasa M, Klumpp C, Briand JP, et al. Targeted delivery of amphotericin B to cells by using functionalized carbon nanotubes. Angewandte Chemie International Edition 2005;44:6358-62.
Jain A, Agarwal A, Majumder S, Lariya N, Khaya A, Agrawal H, et al. Mannosylated solid lipid nanoparticles as vectors for site-specific delivery of an anti-cancer drug. J Controlled Release 2010;148:359-67.
Liu Z, Winters M, Holodniy M, Dai H. siRNA delivery into human t cells and primary cells with carbon‐nanotube transporters. Angewandte Chemie International Edition 2007;46:2023-7.