**2. Lipids and surfactants**

Lipids fulfill various functions in life as membrane constituents, for energy storage, or signaling molecules. Lipids are structurally and functionally diverse organic compounds including fats, oil, and hormones that do not interact appreciably and are insoluble in polar solvents [12]. Lipids are hydrophobic and some of them are amphipathic, which represent a part as hydrophilic and another as hydrophobic. These amphipathic lipids demonstrate

*Lipid Nanoparticulate Drug Delivery Systems: Approaches toward Improvement in Therapeutic… DOI: http://dx.doi.org/10.5772/intechopen.104510*

a unique behavior in water that spontaneously form ordered molecular aggregates with their hydrophilic ends on the outside, in contact with the water, and their hydrophobic part on the inside, shielded from the water. Though biological lipids are similar in chemical linking to polymeric materials used for the delivery of active moiety, however they are not large macromolecules. Lipids are classified in several ways and among them, the major groups classified are fatty acids, fatty acid derivatives, cholesterol, and their derivatives, with lipoproteins. The fatty acids are available in abundant in complexed with fats and phospholipids (**Figure 4**). Fatty acids are also known as carboxylic acids composed of a hydrocarbon chain linked with one terminal of the carboxylic group. However, the fragment of a carboxylic acid lacks a hydroxyl group, known as the acyl group. Moreover, fatty acids in the aqueous phase of physiological condition lose a hydrogen ion (H+ ) to generate an anionic charged carboxylate group (COO− ) and due to a common biosynthetic pathway within the organism, which involves the linking of the two-carbon unit together produces an even number of carbon atoms within fatty acids [13]. These fatty acid lipids are further classified as saturated, unsaturated, monosaturated (MUFA), and polyunsaturated fatty acids (PUFA). The saturated fatty acids specify the bonding of the maximum possible numbers of hydrogen atoms to each carbon in the molecules. Whereas, unsaturated fatty acids indicate one or more double-bonded carbon–carbon molecules. The number of double bonds attributes to mon or polyunsaturated molecules with one double bond and two or more double bonds, respectively. Common saturated and unsaturated fatty acids are lauric acids, myristic acids, palmitic acids, stearic acid, behenic acid, lignoceric acid and palmitoleic acid, oleic acid, gadoleic acid, erucic acid, and nervonic acid, respectively [14]. Furthermore, frequently polyunsaturated fatty acids used are linoleic acid, linolenic acid, and arachidonic acids. Fatty acids are alternatively also obtained from the hydrolysis of hard animal fats, coconut, palm kernel, soybean oils, and from the fractional distillation of crude tall oil. Other fatty acids are derived from petroleum. Physically, most of these fatty acids are liquid at room temperature. The difference in properties is to a large extent related to the presence of saturation and unsaturation within the molecules. Commonly, solid fats are indicated by the dominance of saturated fatty acids and liquid oils are indications of a high level of unsaturated fatty acids [15]. Cholesterol in the free and combined


## **Table 1.**

*Classification of lipoproteins [17].*

state is the most widely occurring sterol in animal tissue. It is an essential compound in the body's production of steroids hormones and bile. It is also an important component for normal skin function. Cholesterol is an important functional excipient used in several pharmaceutical formulations including solid lipid nanoparticles, parenteral mRNA–based drug delivery, vesicular drug delivery, etc. As a part of lipid coating that protects the active drug moiety, and could modulate drug release, enhance the ability of the drug formulation to penetrate cell membranes, and provide a stabilization effect. Recently plant-derived cholesterol including Phytochol®, SyntheChol®, etc., gained significant attention among the researcher due to multifunctional application with lower adverse effects. Lipoproteins are substances made of proteins and fat that carry cholesterol through the bloodstream. Moreover, lipoproteins are complex particles that have a central hydrophobic core of non-polar lipids, primarily cholesterol, ester, and triglycerides [16]. This hydrophobic core is surrounded by a hydrophobic membrane consisting of phospholipids, free cholesterol, and apolipoprotein. Additionally, lipoprotein is a biochemical assembly whose primary function is to transport hydrophobic lipid molecules in water, as in blood plasma or other extracellular fluid. The lipoproteins are broadly classified into several classes, however cholesterol is broadly classified into two categories based on lipoproteins such as highdensity lipoprotein (HDL) and low-density lipoprotein (LDL) (**Table 1**). High-density lipoproteins are generally assumed as "good" and low density as "bad" cholesterol [18].

Surfactants have been diligently associated with humans as early as 2800 BC and continue to be a necessity in day-to-day life with great usage in solubility and entrapment efficacy of drugs used within nanocarriers. The earliest record on the usage of surfactant was recorded as sopay traces in clay cylinders at the Babylonian archeological site in Mesopotamia in 2800 BC [19, 20]. The word "Surfactant" is an abbreviation for "surfaceactive agent", classified as an amphiphilic compound due to the presence of both hydrophilic and hydrophobic groups. Considering hydrophilic group surfactants are broadly classified into four categories such as cationic, anionic, zwitterionic, and non-ionic surfactants. Cationic surfactants contain alkylamine or quaternary ammonium salts that can be absorbed on the negatively charged interface, with the antistatic and disinfectant application. Anionic surfactants contain carboxylic acids salts, sulfonates, sulfate salts, sulfate esters, or phosphate within hydrophobic groups, that offers detergency, foaming, and penetrability use. Zwitterion surfactants contain carboxy betaine, imidazolium betaine, amino ethyl glycine salt, or amine oxide within the hydrophobic structure. They are often used as auxiliary materials to enhance the effectiveness of other surfactants. Non-ionic surfactants have non-dissociable chemical structures in their hydrophilic groups, which are generally used in cosmetics, food emulsifiers, and skin cleaners due to low irritation and toxicity. A wide range of spontaneous, self-assembling surfactants structures in the size range spanning from a few nanometers to tens of micrometers has been reported. Moreover, the role of surfactants in the fabrication of nanocarriers has been proven in various aspects including drug loading, colloidal suspension stability, and *Lipid Nanoparticulate Drug Delivery Systems: Approaches toward Improvement in Therapeutic… DOI: http://dx.doi.org/10.5772/intechopen.104510*

## **Figure 5.**

*Percentage of instances for different surfactants found in the composition of the investigational bioactive incorporated dosage form [21].*

most important formulation stability on long-term storage. The percentage instances for different surfactants found in the compositions of the investigational bioactive incorporated dosage form are presented in **Figure 5**.
