*3.5.1.1 Skin as a barrier and penetration pathways through the skin*

The human body is protected from external harm such as chemical and micro-organism intrusion, UV exposure, dryness and mechanical damage by a natural barrier, the skin.

Hence the multi-layered skin serves as the first line of body defense. The external and internal layers of the skin mainly include the stratum corneum (composed of dead keratinized cells) and below the stratum corneum are the epidermis, dermis and the subcutaneous tissue. The excellent barrier properties of the skin are due to the presence of lipid matrix (containing ceramides, fatty acids, cholesterol and cholesteryl esters) among the keratinized cells which has cement like property [28].

When a drug or an active ingredient is topically applied on the skin surface, there theoretically three different ways through which the drug/active ingredient can penetrate through the skin. These are known as 'The Penetration Pathways'. The penetration pathways are:


The intercellular pathway: This is the most widely known pathway. In this pathway, diffusion of the active ingredient occurs through the stratum corneum via the lipid layers surrounding the corneocytes.

The hair follicle pathway: The hair follicles are surrounded by a dense network of blood capillaries which support efficient penetration. These serve as reservoir for the topically applied active compound.

The transcellular pathway: This is the less understood pathway. Here the drugs are directly transported through the lipid layers and corneocytes to the living cells (**Figure 8**).

#### **Figure 8.**

*Penetration pathways of the active ingredient through the skin. (1) Represents the intercellular pathway, (2) represents the hair follicle pathway and (3) represents the transcellular pathway [28].*

**79**

**4. Conclusions**

*An Update on Nanoemulsions Using Nanosized Liquid in Liquid Colloidal Systems*

molecules they are carrying from degradation and elimination.

grafted to the gel which induces the release insulin by deswelling [44].

also useful for anti-aging, skin care and moisturizing creams [31].

While nanoemulsions are an efficient vehicle for transferring and administering topical drugs into the body, they have some limitations. These are low viscosity, spreadability constraints due to skin as a barrier and rheological properties.

To overcome these problems associated with nanoemulsions, a hydrophilic gelling system was integrated with nanoemulsions to increase the efficiency of transdermal drug delivery. These integrated systems are termed as nano emulgels [43]. Nanoemulgel are usually three-dimensional, spherical gels composed of a cross-linked network of polymeric (natural or synthetic substances) [44]. They are highly preferred over other nanomaterials for drug delivery due to their unique and advantageous features. The most important ones being biocompatibility, stimuli–response behavior softness, their ability to swell up to achieve a controlled, triggered response at the target site. They also protect the guest molecules i.e., the

The versatility of their architecture allows for incorporation of a plethora of guest molecules ranging from inorganic nanoparticles to biomacromolecules like proteins and DNA with suitable modifications of the materials used for their construction without compromising their gel behavior. This multi-functionality and stability is hard to find in other types of nanoparticulate systems [43, 45, 46]. Nanogel properties can be used in various fields to achieve biomedical

Stimuli response behavior: This involves the response of the nanogels to the external environment in the body such as pH, temperature, redox reactions, enzyme concentration etc. It employs the unique ability of the gel network to swell and unwell for this purpose. The nanogels can be composed of different materials depending on the type of response to be initiated. The deswelling and swelling occurs in the presence of changes in pH and concentration of the surrounding environment. For example, a gel network made of polysaccharide functionalized with PBA (aminophenyl boronic acid) is used to detect the fluctuations in glucose concentration, pH, concentration of the cationic and anionic groups bound to the gel and the PBA

Another very important feature is protecting the cargo molecules from degradation and elimination and early clearance carrying small molecules for drug delivery by retaining them within the gel via hydrogen-bonding and hydrophobic interactions. Cationic gel polymers are also useful in carrying molecules of opposite charges such as oligonucleotides, proteins, RNA molecules or a combination of them to achieve multitarget drug delivery. This has been proven to be useful for cancer treatment in animals. These hydrogels show immense amount of versatility, biocompatibility and fluid like transport properties which make them ideal carriers for imaging probes and scanning techniques such as optical imaging and multi-modal scanning [46]. It is

Nanoemulsions are a relatively new class of dispersions which have gained popularity due to their high efficiency in delivery. There have been a lot of efforts and research to develop the preparation methods of nanoemulsions. This emerging component of nanotechnology has become an irreplaceable part and parcel of the cosmetic and pharmaceutical industries. Further research and development in this field can prove to be very crucial for these industries. Nanoemulsions have a huge potential to change the approaches to many fields as discussed in this chapter and

*DOI: http://dx.doi.org/10.5772/intechopen.84442*

*3.5.2 Nanogels*

applications.

*An Update on Nanoemulsions Using Nanosized Liquid in Liquid Colloidal Systems DOI: http://dx.doi.org/10.5772/intechopen.84442*

### *3.5.2 Nanogels*

*Nanoemulsions - Properties, Fabrications and Applications*

natural barrier, the skin.

like property [28].

(**Figure 8**).

penetration pathways are:

• The intercellular pathway

• The hair follicle pathway

• The transcellular pathway

the lipid layers surrounding the corneocytes.

the topically applied active compound.

*3.5.1.1 Skin as a barrier and penetration pathways through the skin*

The human body is protected from external harm such as chemical and micro-organism intrusion, UV exposure, dryness and mechanical damage by a

Hence the multi-layered skin serves as the first line of body defense. The external and internal layers of the skin mainly include the stratum corneum (composed of dead keratinized cells) and below the stratum corneum are the epidermis, dermis and the subcutaneous tissue. The excellent barrier properties of the skin are due to the presence of lipid matrix (containing ceramides, fatty acids, cholesterol and cholesteryl esters) among the keratinized cells which has cement

When a drug or an active ingredient is topically applied on the skin surface, there theoretically three different ways through which the drug/active ingredient can penetrate through the skin. These are known as 'The Penetration Pathways'. The

The intercellular pathway: This is the most widely known pathway. In this pathway, diffusion of the active ingredient occurs through the stratum corneum via

The hair follicle pathway: The hair follicles are surrounded by a dense network of blood capillaries which support efficient penetration. These serve as reservoir for

The transcellular pathway: This is the less understood pathway. Here the drugs are directly transported through the lipid layers and corneocytes to the living cells

*Penetration pathways of the active ingredient through the skin. (1) Represents the intercellular pathway, (2)* 

*represents the hair follicle pathway and (3) represents the transcellular pathway [28].*

**78**

**Figure 8.**

While nanoemulsions are an efficient vehicle for transferring and administering topical drugs into the body, they have some limitations. These are low viscosity, spreadability constraints due to skin as a barrier and rheological properties.

To overcome these problems associated with nanoemulsions, a hydrophilic gelling system was integrated with nanoemulsions to increase the efficiency of transdermal drug delivery. These integrated systems are termed as nano emulgels [43].

Nanoemulgel are usually three-dimensional, spherical gels composed of a cross-linked network of polymeric (natural or synthetic substances) [44]. They are highly preferred over other nanomaterials for drug delivery due to their unique and advantageous features. The most important ones being biocompatibility, stimuli–response behavior softness, their ability to swell up to achieve a controlled, triggered response at the target site. They also protect the guest molecules i.e., the molecules they are carrying from degradation and elimination.

The versatility of their architecture allows for incorporation of a plethora of guest molecules ranging from inorganic nanoparticles to biomacromolecules like proteins and DNA with suitable modifications of the materials used for their construction without compromising their gel behavior. This multi-functionality and stability is hard to find in other types of nanoparticulate systems [43, 45, 46].

Nanogel properties can be used in various fields to achieve biomedical applications.

Stimuli response behavior: This involves the response of the nanogels to the external environment in the body such as pH, temperature, redox reactions, enzyme concentration etc. It employs the unique ability of the gel network to swell and unwell for this purpose. The nanogels can be composed of different materials depending on the type of response to be initiated. The deswelling and swelling occurs in the presence of changes in pH and concentration of the surrounding environment. For example, a gel network made of polysaccharide functionalized with PBA (aminophenyl boronic acid) is used to detect the fluctuations in glucose concentration, pH, concentration of the cationic and anionic groups bound to the gel and the PBA grafted to the gel which induces the release insulin by deswelling [44].

Another very important feature is protecting the cargo molecules from degradation and elimination and early clearance carrying small molecules for drug delivery by retaining them within the gel via hydrogen-bonding and hydrophobic interactions. Cationic gel polymers are also useful in carrying molecules of opposite charges such as oligonucleotides, proteins, RNA molecules or a combination of them to achieve multitarget drug delivery. This has been proven to be useful for cancer treatment in animals.

These hydrogels show immense amount of versatility, biocompatibility and fluid like transport properties which make them ideal carriers for imaging probes and scanning techniques such as optical imaging and multi-modal scanning [46]. It is also useful for anti-aging, skin care and moisturizing creams [31].
