ReviewDelivery of antiinflammatory nutraceuticals by nanoparticles for the prevention and treatment of cancer
Graphical abstract
Introduction
The natural products are valuable sources of bioactive compounds [1], and have been considered the single most successful discovery of modern medicine [2]. In recent years, natural dietary agents have drawn a great deal of attention both from researchers and the general public because of their potential ability to suppress cancers as well as reduce the risk of cancer development [3]. However, a large number of natural products have never been replicated by synthetic medicinal chemistry, which illustrates the importance of drug discovery to identify active compounds and define novel pharmacophores [4]. Also because of their low solubility, many phytochemicals are poorly absorbed by human body, thus one of the most important and interesting applications for encapsulation of phytochemicals is to enhance the bioavailability of phytochemicals by changing the pharmacokinetics and biodistribution [5].
In the past decade, tremendous advancement has been made toward making nanoparticle-based therapeutic products and formulations commercially available. A 2006 European Technological Observatory survey showed that more than 150 pharmaceutical companies were developing nanoscale therapeutics [6]. The idea of controlled drug delivery has been shown to improve the therapeutic index of drugs by increasing their localization to specific tissues, organs, or cells [7], [8]. This approach tends to decrease potential side effects by leaving the normal sensitive cells unharmed. Contemporary systemically administered chemotherapeutic agents are extremely toxic to cancer cells, but can also harm normal cells leading to serious side effects [9]. Controlled drug delivery systems administer the required amount of the drug to the target site and prevent it from circulating until its half-life finishes. The career system associated with site-specific drug delivery can be modulated for better pharmacokinetics and drug bioavailability [5]. More than half of the chemotherapeutic agents currently being administered either are plant derived or semisynthetic in nature. The inevitable share of botanicals, therefore, in the development of modern chemotherapeutics is beyond doubt. Several different classes of active natural products have been documented.
According to the National Nanotechnology Initiative (NNI; http://www.nano.gov) nanotechnologic structures should be only 1–100 nm in at least one dimension. This size requirement can be achieved through various rational designs, including top-down and bottom-up approaches. Nanocarriers have the potential to modify modern drugs by increasing their efficacy, stability, and solubility; decreasing their toxicity; and sustaining their release [10]. Nanoparticulate drug delivery systems using liposomes and biodegradable polymers have attracted increasing attention in recent years. In addition to liposomes and biodegradable polymers, the most common materials for nanocarriers include dendrimers, virus nanoparticles, and magnetic nanoparticles [11] (Fig. 1). Some of the commonly used methods to characterize the nanoparticles are depicted in Fig. 2. The most noticeable nanotechnologic applications in medicine have been related to oncology [12], [13]. In this review, we discuss the recent advances made in approaches for targeting anticancer bioactive natural products in both basic research and clinical trials.
Section snippets
Inflammation, chronic diseases and cancer
A growing body of evidence suggests that many neoplasms are initiated by infections [14]. Some recent reviews have discussed intimate connection between inflammation and cancer [15], [16], [17]. Inflammation is known to contribute to physiological and pathological processes such as wound healing and infection by the activation and directed migration of leukocytes from the venous system to sites of damage [14]. Inflammation functions at all three stages of tumor development: initiation,
Antiinflammatory nutraceuticals
A wide variety of nutraceuticals, the most common of which are shown in Table 1, are known to possess antiinflammatory properties. Extensive research within the last two decades has revealed that curcumin exhibits antioxidative, antiinflammatory, antiapoptotic, antiproliferative, antiinvasive, and antiangiogenic activity [24]. Animal studies have revealed that curcumin can prevent carcinogen-induced tumorigenesis and inhibit the growth of implanted human tumors [25]. Such studies have led to
Nanotechnology
Therapeutic uses of nanotechnology typically involve the delivery of small-molecule drugs, peptides, proteins, and nucleic acids. Nanoparticles have advanced pharmacological effects compared with the therapeutic entities they contain. Active intracellular delivery and improved pharmacokinetics and pharmacodynamics of drug nanoparticles depend on various factors, including their size and surface properties. Nanoparticle therapeutics is an emerging treatment modality in cancer and other
Formulation technologies
Efficient delivery of bioactive agents and peptides and drugs to the systemic circulation and then to a target cell or organ has received considerable attention in medicine because of recent advances in biotechnology.
Role of nanotechnology for nutraceuticals
Nanoformulations of nutraceuticals essentially follow the general principles of nanotechnology. Therefore, the nanotechnology platforms are widely being used create delivery systems for bioactive natural products and nutraceuticals with poor water solubility. The market projections for these technologies suggest a multifold increase in their commercial potential over the next 5 years. Table 5 summarizes a list of nutraceuticals, the materials used for preparing nanoparticles, the size of the
In vivo pharmacokinetics
Site-specific drug delivery is an important area of research that is anticipated to increase the efficacy of drugs and reduce their potential side effects. Biodegradable polymers are currently being used as drug carriers because of their inherent properties of controlled release, enhanced distribution and overall pharmacokinetic availability. The release of loaded drugs from nanoparticles may be controlled in response to changes in environmental conditions, such as temperature and pH.
Conclusion
Overall, these studies indicate that nanotechnology has great potential for delivering nutraceuticals. To fully realize this potential, more clinical trials are needed with nano-formulated nutraceuticals. Abraxan, protein-bound paclitaxel with a mean particle size of approximately 130 nm for injectable suspension, has been approved by the Food and Drug Administration for patients with metastatic breast cancer, but it requires intravenous delivery. Oral delivery of nutraceuticals, however, is
Acknowledgments
We would like to thank Markeda Wade and Stephanie Deming for carefully editing the manuscript and providing valuable comments. We also thank Dr. Chitra Sundaram for assisting with references. This work was supported by MD Anderson's Cancer Center Support Grant from the National Institutes of Health (NIH CA-16 672), a program project grant from the National Institutes of Health (NIH CA-124787-01A2), and a grant from the Center for Targeted Therapy at The University of Texas MD Anderson Cancer
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Present address: Department of Zoology, University of Delhi, Delhi 110007, India.