**1. Introduction**

[191] Apostolopoulos V, McKenzie I, Wilson IA. Getting into the groove: unusual features of peptide binding to MHC class I molecules and implications in vaccine design.

Frontiers in bioscience: a journal and virtual library. 2001;6:D1311-20.

342 Application of Nanotechnology in Drug Delivery

Nanotechnology is the science of manipulating matter where at least one dimension is in the nano-scale. Nanotechnology is a very promising field to the medicinal and pharmaceutical sectors, hence, it plays an important role in enhancing humanity's quality of life. Nanotech‐ nology has many applications in the medical sector, including diagnosis and therapeutic. However, therapeutic uses are considered the main application of nanotechnology in the health sector. Nanotechnology has an important impact on improving therapeutics by facilitating drug delivery, increasing the efficacy of the drug, improving its circulation and stability in addition to decreasing its toxic side effects [1]. Most active compounds that are proven to have certain effects to treat certain ailments or alleviate pain can be categorized as organic compounds. Most active organic compounds are insoluble in aqueous media, have poor bioavailability, instable and most of the time are toxic.

Herbal medicines, or active compounds derived from natural sources suffer from the same limitations of many other drugs [2]. However, in the case of synthesized drugs, many of these problems can be overcome by preparing derivatives of these drugs that retain some of their activities and at the same time enhancing their physical properties to a more suitable form for pharmaceutical formulations. However, herbal medicines are still the main source of drugs and their side effects are much lower than their synthetic counterparts, add to this a deep and strongly rooted trust in many societies in their efficacy to heal or prevent diseases, even though most of the time not proven in a scientific and systematic way. In order to overcome such limitations, many techniques have been employed such as solubilization in a non-polar solvent, preparing them as an injection and/or converting the active ingredients into their salt form in order to enhance their solubility in aqueous medium. However, these methodologies also suffer from various disadvantages. These include the toxicity of the solubilizing agent,

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the actual or real activity of the salt form, the need for further studies to insure the presence of the bioactive form of the drug and the extent of its bioavailability. In this aspect, nanotech‐ nology is a very promising tool for enhancing the use of herbal medicines, or in more accurate words, to re-discover their full potential in pharmaceutical formulation. Extensive libraries of nanoparticles-that can be used for the delivery of natural bioactive compounds to a certain target-have been studied. These different nanoparticles can be designed, prepared in different shapes, sizes, compositions, functionalized and modified chemically/physically to suite specific properties depending on the characteristics of both the drug and the targeted organ. These nanoparticles can be anything from emulsion and micro-emulsions, dendrimers, fullerenes, liquid crystals, quantum dots, nano rods, solid lipid nanoparticles (SLN), lipo‐ somes, gels and many other different types.

ent(s). The parent compound is phenol but most of these naturally occurring compounds are polyphenolics, which to date, exceeds 8000 structurally identified compounds. Plant polyphe‐ nolics are grouped into different classes depending on their chemical structure. Flavanoids are the largest and most important group of natural polyphenolics with more than 6000 molecules identified so far. Other classes include phenolic quinones, lignans, xanthones, coumarines, polymeric lignins and tanins [5]. Within each class of compounds, the variations around the basic chemical skeleton essentially concern the degrees of oxidation, hydroxylation, methyla‐ tion, glycosylation and the possible connections to other molecules (primary metabolites such

Nanoflora — How Nanotechnology Enhanced the Use of Active Phytochemicals

http://dx.doi.org/10.5772/58704

345

Polyphenols were the focus of special attention as a result of the so-called Mediterranean diet rich in fruits and vegetables. This diet appears to protect against cardiovascular diseases in addition to potential beneficial health properties, as evidenced by several epidemiological studies showing that diets rich in fruits and vegetables are generally associated with a lower cancer incidence and other diseases, such as inflammatory or cardiovascular pathologies [7].

The bioavailability of the orally administrated polyphenols is very low due to their low water solubility, poor absorption, extensive and rapid metabolism. To overcome these problems, several bioactive polyphenols were formulated into various pharmaceutical formulations that

Among the types of naturally occurring polyphenols, flavonoids (Figure 1) are a large and a highly diverse group of structurally related secondary metabolites produced by plants. The main flavonoids subclasses include flavones (Figure 1a), flavonols (Figure 1b), flavans (Figure 1c), flavanones (Figure 1d) in addition to dihidroflavanols (Figure 1e), isoflavons (Figure 1f)

**O**

**O**

**O**

**a b c**

**OH**

**O**

**d e f**

Flavonoids received considerable attention due to their wide biological activities. Many of them are known to possess hepatotoxic, antiinflammatory, antimicrobial, antiviral, anti-allergic and anti-ulcer effects. Also, flavonoids are known to be potent antioxidants with free radical scavenging abilities [9, 10]. Some flavonoids are known to provide protection against cardiovascular mortality. Moreover, they have been shown to inhibit the growth of various cancer cell lines *in vitro*, and reduce tumor development in experimental animals [11]. Flavanoids, as natural compounds have several great advantages over therapeutic agents because many diets are rich in polyphenolic

Flavonoids received considerable attention due to their wide biological activities. Many of them are known to possess hepatotoxic, anti-inflammatory, antimicrobial, antiviral, anti-

Lignans (Figure 2) are among the important polyphenolic compounds that are recognized with a wide spectrum of biological activities. These compounds generally represent a group of dimeric phenylpropanoids where two C6-C3 are attached by its central carbon C-8.

Lignans are known for their antiviral, anticancer, cancer prevention, anti-inflammatory, antimicrobial and antioxidant activities. Also, lignans are known for their immunosuppressive, hepatoprotective and osterporosis prevention effects. Podophyllotoxin (Figure 3) has long been known to possess anti-mitotic activity with early clinical trials indicating its high efficacy. Unfortunately, this compound is known to be toxic limiting its direct application as a drug **[**12**]**. To solve the problem of toxicity, several modifications were made to the podophyllotoxin structure in hope of obtaining compounds with low toxicity but retain the desired activities of the parent compound.

**1**

**7 8 9**

**3 2**

**5 6**

**4**

**a b**

**OH**

**O**

**O**

**O**

**1'**

**7' 8' 9'**

**2' 3'**

**6' 5'**

**4'**

5

as carbohydrates, lipids, proteins, or phenolic secondary metabolites [6].

could improve their bioavailability.

**O**

**O**

**O**

**O**

**Figure 1.** Basic structures of some flavonoids' backbone

**Figure 2.** Basic structure of lignans: a) Phenylpropanoid unit; b) Lignan structure

**1**

**7**

**8**

**9**

**6**

**2**

**5**

**3 4**

compounds [9]. The therapeutic potential of flavonoids makes them valuable targets for drug design [8].

**Figure 1.** Basic structures of some flavonoids' backbone

and biflavones. [8].

In this chapter, a brief focus on herbal medicines, nanotechnological approaches to enhance their promised action will be reviewed and discussed. At the end, successful stories of nanoparticle loaded active phytochemicals that reached the market will be presented as case studies in this field.
