Nanocurcumin: a novel antifilarial agent with DNA topoisomerase II inhibitory activity.
OBJECTIVE
The aim of this study is to evaluate the antifilarial, antiwolbachial and DNA topoisomerase II inhibitory activity of nanocurcumin (nano-CUR).


METHODS
Nano-CUR formulations (F1-F6) were prepared using free radical polymerization and were characterized by particle size, morphology, encapsulation efficiency and in vitro release kinetics. Antifilarial potential was evaluated in vivo against Brugian filariasis in an experimental rodent model, Mastomys coucha, by selecting the formulation that maximized parasite elimination characteristics. Wolbachial status was determined by PCR and a relaxation assay was used to estimate DNA topoisomerase II inhibitory activity.


RESULTS
Nano-CUR (F3) having a 60 nm diameter and 89.78% entrapment efficiency showed the most favorable characteristics for the elimination of filarial parasites. In vivo pharmacokinetic and organ distribution studies demonstrate significantly greater C(max) (86.6 ± 2.56 ng ml(-1)), AUC0-∞ (796 ± 89.8 ng d ml(-1)), MRT (19.5 ± 7.82 days) and bioavailability of CUR (70.02%) in the organs from which the adult parasites were recovered. The optimized nano-CUR (F3) (5 × 5 mg/kg, orally) significantly augmented the microfilariciadal and adulticidal action of CUR over free CUR (5 × 50 mg/kg, orally) or Diethylcarbamizine (50 mg/kg, orally) against the Brugia malayi Mastomys coucha rodent model. The PCR results showed complete elimination of wolbachia from the recovered female parasites. Interestingly, nano-CUR was also found to be a novel inhibitor of filarial worm DNA topoisomerase II, Setaria Cervi in vitro.


CONCLUSIONS
This study recognizes the beforehand antimicrofilarial, antimacrofilarial, anti-wolbachial activity of nano-CUR (F3) over free forms and additionally its strong inhibitory action against the major target filarial parasite enzyme DNA topoisomerase II in vitro.
Nanomedicine Lab, Hamdard Nanobiotechnology Center for Advanced Research, Faculty of Engineering & Interdisciplinary Sciences , Hamdard University, New Delhi , India .
Mohammad
M
Ali
Mohammad
M
Afzal
Sekh
S
Abdul Nasim
Istaq
I
Ahmad
D000818:Animals; D002009:Brugia / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D003474:Curcumin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000469:parasitology; D005369:Filaricides / Q000008:administration & dosage / Q000627:therapeutic use*; D006790:Host-Parasite Interactions / Q000502:physiology; D008297:Male; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D051381:Rats; D013499:Surface Properties; D014018:Tissue Distribution; D059005:Topoisomerase II Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
D004337:Drug Carriers; D005369:Filaricides; D059005:Topoisomerase II Inhibitors; D003474:Curcumin
Brugia malayi; DNA topoisomerase II; diethylcarbamizine; lymphatic filariasis; nanocurcumin; wolbachia