102-1 食生系碩士在職專班專題討論 5101043001 何一正

Curcumin nanoformulations:a future nutraceutical for bioavaliability

Abstract

Curcumin, a natural diphenolic compound derived from turmeric Curcuma longa. In recent years, scientists has been focused on curcumin due to its varieties bio-function without side effects such as cancer, diabetes, cardiovascular diseases, arthritis, Alzheimer's disease, etc. only a few novel multifunctional and composite nanosystem strategies offer simultaneous therapy as well as imaging characteristics. The challenges to developing curcumin delivery platforms and up-to-date solutions for improving curcumin bioavailability as bioactive nanoparticle drug potential for therapy.

Nanoparticle encapsulation improves oral bioavailability of curcumin

Curcumin, a derived product from common spice turmeric that is safe and beneficial in several aliments was formulated into biodegradable nanoparticles with a view to improve its oral bioavailability [1]. The curcumin encapsulated nanoparticles prepared by emulsion technique were spherical in shape with particle size of 264 nm (polydispersity index 0.31) and 76.9% entrapment at 15% loading. Curcumin loaded PLGA nanoparticles were prepared by emulsion–diffusion– evaporation method. Of the various stabilizers screened for preparation of nanoparticles, CTABgave particles of smallest size compromising the entrapment, while those with PVA gave particles with highest entrapment but larger size. Pluronic F-68 and Vit. ETGPS produced particles of intermediate size and entrapment efficiency. Comparative in vivo plasma concentration vs. time profiles of different curcumin formulations. The in vivo pharmacokinetics revealed that curcumin entrapped nanoparticles demonstrate at least 9-fold increase in oral bioavailability when compared to curcumin administered with piperine as absorption enhancer.[2]. Recently developed curcumin organogel was used as the oil phase in the curcumin nanoemulsion formulation. Tween 20 was selected as the emulsifier on the basis of maximum in vitro bioaccessibility of curcumin in the nanoemulsion. In vitro lipolysis profile revealed that the digestion of nanoemulsion was significantly faster and more complete than the organogel. Permeation experiments on Caco-2 cell monolayers suggested that digestion-diffusion was the major absorption mechanism for curcumin in the nanoemulsion [3]. The curcumin encapsulated in casein nanoparticles had higher biological activity, as assessed by antioxidant and cell proliferation assays, than pristine curcumin, likely due to the improved dispersibility. To simplify sample preparation, sodium caseinate (NaCas), a commercially available ingredient produced by acid precipitation of caseins from bovine milk followed by neutralization using sodium hydroxide for spray-drying. This simple approach may be applied to encapsulate various lipophilic bioactive compounds [4]. The conjugated curcumin with silica nanoparticles to improve its aqueous solubility and hence to make it more bioavailable. Conjugation and loading of curcumin with silica nanoparticles was further examined with transmission electron microscope (TEM) and thermogravimetric analyzer. conjugation of curcumin with silica nanoparticles by using a simple wet chemical method. This protocol envisages good bioavailability of the curcumin molecule, keeping its therapeutic activity intact. Further, this conjugate was studied against cancerous and primary cell lines. Cytotoxicity analysis of synthesized silica:curcumin conjugate was studied against HeLa cell lines as well as normal fibroblast cell lines. This study shows that silica:curcumin conjugate has great potential for anticancer application [5].

Examination of the Permeation Mechanism of Curcumin in the Nanoemulsion

The permeation mechanism for curcumin in the organogel-based nanoemulsion was investigated using Caco-2 cell monolayers to mimic the small intestine epithelium. There are two possible mechanisms for curcumin nanoemulsion permeation: (1) Nanoemulsions would be digested by lipase and simultaneously curcumin is solubilized by bile salts-fatty acids mixed micelles. Subsequently, solubilized curcumin passively diffuses across the epithelium layer. This represents the classic digestion−diffusion route applicable for all the regular lipid-based formulations; (2) intact nanoemulsions, because of their small size, would be able to directly diffuse across the small intestine layer without digestion [2-4].

Bioactive of curcumin nanoparticles

nanoparticulate curcumin was comparatively more effective than native curcumin against different cancer cell lines under in vitro condition with time due to enhanced cellular uptake resulting in reduction of cell viability by inducing apoptosis. Molecular basis of apoptosis studied by western blotting revealed blockade of nuclear factor kappa B (NFkB) and its regulated gene expression through inhibition of IkB kinase and Akt activation. In mice, nanoparticulate curcumin was more bioavailable and had a longer half-life than native curcumin as revealed from pharmacokinetics study. Thus, the results demonstrated nanoparticulate curcumin may be useful as a potential anticancer drug for treatment of various malignant tumors [6]. ALG-CS-PF127 composite NPs have the potential to meet some of the challenges of nanoformulation of hydrophobic drugs for delivery to cancer cells. These composite NPs have a suitable size distribution, drug encapsulation efficiency, and drug release kinetics. All the three components of the composite NPs—namely ALG, CS, and PF127—have reported biocompatibility [7].

Conclusions

These varieties types of NPs have been establish to be appropriate for the encapsulation or loading of curcumin to get better its effects in bioavailability and biofunction. The characteristics of these curcumin nanoformulations can be modified according to the specific obligation for inducing cellular death by various mechanisms. Overall, our understanding from the available literature is that the use of curcumin nanoparticles in chemotherapy for cancer treatment and other disease is a facile modality that improves existing curcumin therapies by targeting tumors or proteins and by reducing the drug dose required. The safety of the various curcumin nanoformulations and their efficacy in the cell-line models draw attention to their potential for estimate in in vivo models. In the feature, the human trials need to be conducted to establish their effectiveness in clinical applications as an improved therapeutic modality for disease treatment.

102-1食生系碩專班專題討論 5101043001 何一正

References

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[2] Cui J, Yu B, Zhao Y, Zhu W, Li H, Lou H, et al. Enhancement of oral absorption of curcumin by self-microemulsifying drug delivery systems. International Journal of Pharmaceutics. 2009;371:148-55.

[3] Yu H, Huang Q. Improving the oral bioavailability of curcumin using novel organogel-based nanoemulsions. Journal of agricultural and food chemistry. 2012;60:5373-9.

[4] Pan K, Zhong Q, Baek SJ. Enhanced dispersibility and bioactivity of curcumin by encapsulation in casein nanocapsules. Journal of agricultural and food chemistry. 2013.

[5] Gangwar RK, Tomar GB, Dhumale VA, Zinjarde S, Sharma RB, Datar S. Curcumin conjugated silica nanoparticles for improving bioavailability and its anticancer applications. Journal of agricultural and food chemistry. 2013;61:9632-7.

[6] Mohanty C, Sahoo SK. The in vitro stability and in vivo pharmacokinetics of curcumin prepared as an aqueous nanoparticulate formulation. Biomaterials. 2010;31:6597-611.

[7] Das RK, Kasoju N, Bora U. Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells. Nanomedicine: Nanotechnology, Biology and Medicine. 2010;6:153-60.

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