ORIGINAL ARTICLE A comparative study of PNIPAM nanoparticles of curcumin, demethoxycurcumin, and bisdemethoxycurcumin and their effects on oxidative stress markers in experimental stroke Niyaz Ahmad & Sadiq Umar & Mohammad Ashafaq & Mohd Akhtar & Zeenat Iqbal & Mohd Samim & Farhan Jalees Ahmad Received: 21 March 2013 / Accepted: 23 May 2013 # Springer-Verlag Wien 2013 Abstract Oxidative stress and inflammatory damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The development of new strategies for enhancing drug delivery to the brain is of great importance in diagnostics and therapeutics of central ner- vous diseases. The present study examined the hypothesis that intranasal delivery of nanoformulation of curcuminoids would reduce oxidative stress-associated brain injury after middle cerebral artery occlusion (MCAO). The rats were subjected to 2 h of MCAO followed by 22 h reperfusion, after which the grip strength, locomotor activity was performed. The effects of treatment in the rats were assessed by grip strength, locomotor activity and biochemical studies (glutathione perox- idase, glutathione reductase, lipid peroxidation, superoxide dismutase, and catalase) in the brain. Pretreatment with poly- meric N-isopropyl acryl amide (PNIPAM) nanoparticles for- mulation of all three curcuminoids (curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC)) at doses (100 μg/kg body weight) given intrana- sally was effective in bringing significant changes on all the parameters. While nanoformulation of curcumin at a dose of 100 μg/kg body weight was most active in the treatment of cerebral ischemia as compared to others nanoformulation of curcuminoids. The potency of antioxidant activity significant- ly decreased in the order of PNIPAM nanoformulation of Cur > DMC >> BDMC, thus suggesting the critical role of methoxy groups on the phenyl ring. Keywords Curcumin . Demethoxycurcumin . Bisdemethoxycurcumin . MCA occlusion . Oxidative stress . PNIPAM nanoparticles Introduction Stroke is a global public health concern and one of the leading cause of mortality and morbidity, with astro- nomical financial repercussions on health systems worldwide (Allen and Bayraktutan 2009 ; Ashafaq et al. 2012). Cerebral ischemic insult usually causes irreversible deterioration of the central nervous system (CNS) (Kim et al. 2007). After the onset of cerebral ischemia, inflammatory process triggers the acceleration of the early onset and functions as a determinant factor in severity of cerebral damage, morbidity, and mortality (Berner et al. 2005). Oxidative stress has always been implicated in the machinery of ischemia–reperfusion Handling Editor: Damjana Drobne N. Ahmad : Z. Iqbal : F. J. Ahmad (*) Nanomedicine lab, Department of Pharmaceutics, Faculty of Pharmacy, Hamdard University, New Delhi 110062, India e-mail: farhanja2000@gmail.com N. Ahmad e-mail: niyazpharma@gmail.com S. Umar : M. Ashafaq Department of Medical Elemental and Toxicology, Faculty of Science, Hamdard University, New Delhi 110062, India M. Akhtar Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi 110062, India M. Samim Department of Chemistry, Faculty of Science, Hamdard University, New Delhi 110062, India Protoplasma DOI 10.1007/s00709-013-0516-9