S. Dhivya*, DR. A. N. Rajalakshmi
Department of Pharmaceutics,
Mother Theresa Post Graduate and Research Institute of Health Sciences,
Gorimedu, Puducherry, India


ABSTRACT: Design and development of herbal nanoparticles has become a frontier research in the nanoformulation arena. Curcumin, a hydrophobic polyphenol (diferuloyl methane) is a potent phytomolecule obtained from turmeric (Curcuma longa, Family-Zingiberaceae) has a wide range of biological activities in chronic diseases and has wide therapeutic efficacy. But the clinical application of curcumin was limited due to its poor water solubility, rapid metabolism and rapid elimination which ultimately results in poor bioavailability upon oral administration. Therefore introduction of nanotechnology provides a solution towards increased bioavailability of curcumin. In this review, an overview of curcumin nanoparticles is discussed.

Reference Id: PHARMATUTOR-ART-2544

PharmaTutor (Print-ISSN: 2394 - 6679; e-ISSN: 2347 - 7881)

Volume 5, Issue 12

Received On: 02/08/2017; Accepted On: 14/08/2017; Published On: 01/12/2017

How to cite this article: Dhivya S, Rajalakshmi AN;Curcumin Nano drug delivery systems: A Review on its type and therapeutic application; PharmaTutor; 2017; 5(12); 30-39

Curcumin (also known as curcumin-I) [1], is the principle curcuminoid found in Indian curry spice turmeric (Curcuma longa, Family-Zingiberaceae). The other curcuminoids present in turmeric are demethoxycurcumin (curcumin-II) [2], bisdemethoxycurcumin (curcumin-III) [3] and recently cyclocurcumin [4] is identified. Curcumin is a potent phytomolecule with a wide range of biological activities [5]. Curcumin is a principle nutraceutical molecules along with other curcuminoids and it has been used in the food and pharmaceuticals industries[6]. Its clinical applications are limited largely due to its poor solubility and rapid metabolism, which results in poor bioavailability.  Curcumin is characterized with extremely low solubility in water (11ng/ml) and significant presystemic biotransformation, mainly via glucuronide and sulfate conjugation. The maximum oral dose of 8 gm/day of curcumin does not produce any toxic effects [7].

With the ongoing development of nanotechnology, the nanoparticles have its own importance in novel drug delivery system. The emergence of nanoscience, which is the creation and utilization of materials and tools on nanometer scale, has exerted a deep influence on numerous industries and particularly the pharmaceutical industry. The application of nanoparticle formulation will deliver new approaches for enhancement of solubility, stability, bioavailability and pharmacological activity and ability to avoid physical and chemical degradation. Therefore introduction of nanotechnology in curcumin provides a solution towards increased bioavailability and therapeutic efficacy.

Today, due to technological innovations nontoxic, biocompatible, inexpensive and biodegradable nanoparticles with various colloidal dimensions are being developed to enhance the penetration ability, reduce the frequency of doses, toxicity and to improve the therapeutic efficacy [8-10].


Chemical Structure of curcuminoids

Need of novel drug delivery system for curcumin
Curcumin is highly unstable in acidic pH of the stomach and degraded at alkaline pH before reaching to the blood and other constituents might be metabolized by the liver. Resulting, the optimum quantity of the curcumin may not reach the blood resulting in no/less therapeutic effect. Nanocarriers applying to curcumin will carry optimum amount of the drug to their site of action bypassing all the barriers such as acidic pH of stomach, liver metabolism and increase the prolonged circulation of the drug into the blood due to their small size. So curcumin was selected as feasible drug candidate for delivery through a nano delivery system because of the following properties

• To improve the solubility
• To enhance the bioavailability
• To reduce the dose.
• To target the site of action.
• To control the release of the drug

Types of Curcumin Nano drug delivery systems
• Liposomes
• Polymeric Nanoparticles
• Solid lipid nanoparticals
• Polymeric micelles
• Magnetic nanoparticals
• Nanogels
• Gold Nanoparticles
• Silver Nanoparticles

Liposomes: Liposomes are closed spherical vesicles consisting of a lipid bilayer that encapsulates an aqueous phase in which drugs can be entrapped [11]. With the advantages of high biocompatibility, easy preparation, chemical versatility, and simple modulation of their pharmacokinetic properties by changing the chemical composition of the bilayer components, they have been used to improve the therapeutic activity and safety of drugs for many years [12]. So, liposomes have found wide application in enhancing curcumin’s bioavailability and efficacy. In this regard, to enhance the solubility of curcumin, Rahman et al., prepared beta-cyclodextrin curcumin inclusion complexes that entrapped both native curcumin and the complexes separately into liposomes. All curcumin-containing formulations were effective in inhibiting cell proliferation in in vitro cell culture [13]. Chen et al., reported the effects of different liposomal formulations on curcumin stability in phosphate buffered saline, human blood, plasma, and culture medium. Liposomal curcumin showed a higher stability than free curcumin in phosphate buffered saline (PBS) [14].

Polymeric Nanoparticles:  Due to the small size and excellent biocompatibility, polymeric nanoparticles can circulate in the bloodstream for a longer time; thus, specific therapy can be achieved [15]. The widely researched synthetic polymers include chitosan [16,17], poly(D,L-lactideco-glycolide) (PLGA)[18-20], and PEG [21] for the cucrcumin nanoparticle formation. Moreover, polymers can be combined to form copolymers, which could be a promising drug carrier for the site targeting and sustained action.
Solid Lipid Nanoparticles (SLNs): SLNs are made of natural or synthetic lipid or lipoid, such as lecithin and triglycerides, which are solid at human physiological temperature [22]. SLNs offer unique properties such as smaller size, larger surface area, interaction of phases at the interfaces, and these are attractive for their ability to improve performance of neutraceuticals, pharmaceuticals and other materials. Solid lipid nanoparticles possess a solid lipid core matrix that can solubilize Lipophilic molecules. The lipid core is stabilized by surfactants (emulsifiers). For pharmaceutical applications, all formulation excipients must have Generally Recognized as Safe (GRAS) status to achieve and maintain a solid lipid particle upon administration, the lipid nanoparticles melting point must exceed body temperature (37 °C) [23]. Kakkar et al., prepared curcumin-loaded solid lipid nanoparticles (C-SLNs) for the improvement of its oral bioavailability [24]. Dadhaniya et al., examined the adverse effects of a new solid lipid curcumin particle in rats [25].

Polymer Micelles: Micelles are lipid molecules that arrange themselves in a spherical form in aqueous solutions with a very narrow range from 10 to 100 nm in size, which makes them more stable towards dilution in biological fluids [26]. The functional properties of micelles are based on amphiphilic block copolymers, which come together to form a nanosized core/shell structure in aqueous media. Polymeric micelles can serve as transporters of water-insoluble drugs such as curcumin, which can augment the drug’s efficiency by targeting definite cells or organs; therefore, fewer drugs accumulate in healthy tissues and their toxicity reduces, and occasionally higher doses can be administered [27]. In this regard, to overcome the poor water solubility of curcumin, Liu et al., prepared curcumin loaded biodegradable self-assembled polymeric micelles for sustained release[28]. In addition, the preparation of curcumin-loaded micelles based on amphiphilic Pluronic/ polycaprolactone block copolymer was investigated by Raveendran et al., which proved to be efficient in enhancing curcumin’s aqueous solubility [29]. Thus the micellar system is efficient for solubilization, stabilization, and controlled delivery of curcumin.

Magnetic Nanoparticles: Magnetic drug targeting, in which a drug is conjugating with a magnetic material under the action of the external magnetic field. Drug-loaded magnetic nanoparticles can accumulate in target tissue areas under the action of the external magnetic field; the drug then releases from the particles in a controllable way [30]. Yallapu et al., [31] introduced magnetic drug carriers with a pluronic polymer (F127) shell for controlled delivery of curcumin. A nanosized magnetofluorescent water-dispersible Fe3O4-curcumin conjugate with chitosan or oleic acid asits outer shell and entrapped curcumin was designed by Tran et al., [32]. The Fe3O4-curcumin conjugate exhibited a high-loading cellular uptake that was distinctly observed by magnetic and fluorescent methods and was also shown to be a good candidate for a dual (optical and magnetic) imaging probe.

Nanogels: Nanogels are cross-linked three-dimensional polymer chain networks which are created through covalent linkages and can be customized to gel networks with biocompatible and degradable properties. Nanogels demonstrate excellent potential for systemic drug delivery that should have a few common features including a smaller particle size (10–200 nm), biodegradability and/or biocompatibility, prolonged half-life, high stability, higher amount of drug loading and/or entrapment, and molecules protection from immune system. Goncalves et al., [33] applied a self-assembled dextrin nanogel as curcumin delivery system by using dynamic light scattering and fluorescence measurements. Various nanogel properties can be attained by altering the chemical functional groups, cross-linking density, and surface-active and stimuli-responsive elements. Wu et al., [34] designed a class of water-dispersible hybrid nanogels for intracellular delivery of hydrophobic curcumin.

Gold nanoparticles: With the optical and electrochemical uniqueness, gold nanoparticles have proven to be a potent apparatus in nanomedicinal requests [35].  Moreover, the stability of AuNPs and their capability to combine with biomolecules are their other outstanding properties. AuNPs are studied broadly as imperative drug delivery vectors due to some of their characteristic aspects, such as low cytotoxicity, tunable surface features, and stability in in vivo conditions, and can be easily synthesized and functionalized.  Rajesh et al., [36] used polyvinyl pyrrolidone (PVP) as a proven drug carrier to curcumin conjugation with AuNPs to enhance solubility of curcumin. In a study by Singh et al., [37] curcumin was bound on the surface of AuNPs in order to increase the bioavailability of it. Manju and Sreenivasan [38] also formulated a simple method for the fabrication of water-soluble curcumin conjugated AuNPs to target various cancer cell lines. AuNPs also cause targeting and sustained release of curcumin and an excellent antioxidant activity.

Silver Nanoparticles: Silver is usually utilized as an incredibly efficient material for antimicrobial utility [39]. Silver nanoparticles are identified for their brilliant optoelectronic properties originated from surface plasmon resonance. They have shown excellent antimicrobial activity compared to other available silver antimicrobial agents. Sodium carboxylmethyl cellulose silver nanocomposite films were attempted for antibacterial applications, so, to improve their applicability, novel film-silver nanoparticle curcumin complexes have been developed [40]. In addition, silver nanoparticles could protect cells against HIV1 infection and help with the wound healing process and also have essential function as an anti-inflammation, an antiviral, and an anticancer agent [41]. So, the combination of silver nanoparticles and curcumin, besides prolonged therapeutic outcomes and sustained release, has several other useful effects such as anti-inflammatory, anti-infection, anticancer, and wound healing.



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