ApoE3 Mediated Poly(butyl) Cyanoacrylate Nanoparticles Containing Curcumin: Study of Enhanced Activity of Curcumin against Beta Amyloid Induced Cytotoxicity Using In Vitro Cell Culture Model

• Published in: Molecular pharmaceutics Vol. 7; no. 3; pp. 815 - 825
• Main Authors: Mulik, Rohit S, Mönkkönen, Jukka, Juvonen, Risto O, Mahadik, Kakasaheb R, Paradkar, Anant R
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 07-06-2010
• Subjects: Alzheimer Disease - drug therapy; Alzheimer Disease - metabolism; Amyloid beta-Peptides - metabolism; Amyloid beta-Peptides - physiology; Apolipoprotein E3 - chemistry; Apoptosis - drug effects; Caspase 3 - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Curcumin - chemistry; Curcumin - therapeutic use; Enbucrilate - chemistry; Flow Cytometry; Humans; Models, Theoretical; Nanoparticles - chemistry; Polymers - chemistry; Reactive Oxygen Species - metabolism; X-Ray Diffraction; targeted nanoparticles; Beta amyloid; apolipoprotein E3; Alzheimer’s disease; apoptosis; cytotoxicity; curcumin
• ISSN: 1543-8384; 1543-8392
• DOI: 10.1021/mp900306x

Beta amyloid plays a main role in the pathophysiology of Alzheimer’s disease by inducing oxidative stress in the brain. Curcumin, a natural antioxidant, is known to inhibit beta amyloid and beta amyloid induced oxidative stress. However, low bioavailability and photodegradation are the major concerns for the use of curcumin. In the present study, we have formulated apolipoprotein E3 mediated poly(butyl) cyanoacrylate nanoparticles containing curcumin (ApoE3−C-PBCA) to provide photostability and enhanced cell uptake of curcumin by targeting. Prepared nanoparticles were characterized for particle size, zeta potential, entrapment efficiency and in vitro drug release. The entrapment of curcumin inside the nanoparticles was confirmed by X-ray diffraction analysis. Physicochemical characterization confirmed the suitability of the method of preparation. The photostability of curcumin was increased significantly in nanoparticles compared to plain curcumin. In vitro cell culture study showed enhanced therapeutic efficacy of ApoE3−C-PBCA against beta amyloid induced cytotoxicity in SH-SY5Y neuroblastoma cells compared to plain curcumin solution. Beta amyloid is known to induce apoptosis in neuronal cells, therefore antiapoptotic activity of curcumin was studied using flow cytometry assays. From all the experiments, it was found that the activity of curcumin was enhanced with ApoE3−C-PBCA compared to plain curcumin solution suggesting enhanced cell uptake and a sustained drug release effect. The synergistic effect of ApoE3 and curcumin was also studied, since ApoE3 also possesses both antioxidant and antiamyloidogenic activity. It was found that ApoE3 did indeed have activity against beta amyloid induced cytotoxicity along with curcumin. Hence, ApoE3−C-PBCA offers great advantage in the treatment of beta amyloid induced cytotoxicity in Alzheimer’s disease.