**4.1 Oral route**

As it was already said that the solubility of the drug plays an important role in bioavailability of the drug, it is important to improve the solubility so as to increase the bioavailability (**Figure 1**). When a drug is being incorporated in microemulsion, compared to conventional medications, the microemulsion can increase the absorption, increase the therapeutic efficacy and also decrease the drug toxicity [12]. Apart from the solubility, in many of the cancers, the MDR (multi drug resistance) plays an important role; it does not allow the anti-cancer drugs to produce its activity by creating an efflux system. But, the microemulsion has the capacity to overcome this efflux system and deliver the anti-cancer drug in a more efficient manner. One such study has been carried out by Ding Qu et al., in which a multicomponent microemulion has been formulated consisting of coix seed oil, ginsenoside Rh2 loaded with etoposide. This formulation has been useful in inhibiting the Pgpefflux, which may because of the use of G-Rh2 that has the capacity to interact with the Pgp-efflux and in addition, the formulation has produced a synergistic activity which may be because of the oils used in this formulation, that also possess some anti-cancer activity [48].

Apart from the normal microemulsion, the microemulsion can be used as a preconcentrate in order to improve the bioavailability as well as therapeutic effect of anti-cancer drug. As it was said already, one such form of preconcentrate is called the Self-microemulsifying drug delivery system (SMEDDS). They are also similar to

#### **Figure 1.**

*Represents the different routes of administration of microemulsion for targeting various cancers (Created with Biorender).*

*Perspective Chapter: Microemulsion as a Game Changer to Conquer Cancer with an Emphasis… DOI: http://dx.doi.org/10.5772/intechopen.101479*

that of micro-emulsion, whereas being a preconcentrate, they does not have water in their formulation. During this case a question arises in our mind stating that were does the aqueous phase come from. Well, the SMEDDS being a preconcetrae when administered, it gets emulsified with the help of Gastro intestinal fluid, thereby forming a microemulsion. This type of self-emulsifying microemulsion serves more advantage as compared to the existing microemulsion. Since, the water is not involved, enhanced physical and chemical stability can be obtained on long term storage [49]. It also has the ability to decrease the gastric irritation caused by some of the anti-cancer agents. Studies are also being carried out with SMEDDS for the rehabilitation of cancer. Triptolide obtained from *Tripterygium wilfordii* possess anti-cancer activity, at the same time they also have low solubility, gastrointestinal irritation and also poor bioavailability. Triptolide has been incorporated to SMEDDS in order to overcome the above said effects and their anticancer activity on gastric cancer has also been identified [50].

#### **4.2 Parentral route**

Microemulsion can be delivered via the parenteral route instead of suspension that is not suitable for the parenteral route. Compared to liposomes, they are having a good stability when given through parenteral route. When a microemulsion is loaded with the higher concentration of the drug, the frequency of administration can be decreased [51]. Some of the drugs have to be given through the parenteral route because in order to overcome the degradation of the drug, instability of the drug, low bioavailability of the drug, decreased therapeutic activity of the drug due to oral administration. At some instance, the parenteral route of administration of the drug itself can lead to precipitation of the drug when mixed with the infusion fluids. Thus, in those cases it is important to incorporate the drug into a suitable vehicles or carrier to obtain an improved bioavailability an increased therapeutic activity without any capillary blockade. But incorporation of more solvents or aqueous solutions may cause mild to severe side effects. In these circumstances, the microemulsion comes into play, because of their thermodynamic stability. Jayesh Jain et al. has worked on etoposide, in which they have formulated the microemulsion for parenteral administration. Since, the etoposide need to be administered slowly through the intravenous infusion, it is important to detect the changes when they are mixed with infusion fluids. As a result they observed that the microemulsion was not having a drug precipitation up to a certain concentration of drug. But as the concentration of drug increases the precipitation serves as a limitation. Thus, more study on the reason for the drug precipitation should be understood [52].

The microemulsion also serve various advantages while comparing other colloidal carriers, microemulsions can deliver the hydrophobic drugs, as they can solubilize those types of drugs and also the scale-up can be done easily compared to other carriers.

It is important to know the right excipients for the preparation of microemulsions for parenteral delivery, as the parenteral delivery deal with only few excipients. Those excipients should also be biocompatible, non- irritant and a sterilizable one. Other than these properties, the excipients that are used for preparation of microemulsion for parenteral delivery is similar to that of the normal microemulsion. They consist of oily phase, surfactant, co-surfactant and the aqueous phase. But while using these components during the formulation, certain factors should be considered like [53]:

• Long term usage of oily phase for parenteral administration should be determined.


#### **4.3 Nasal route**

Glioblastoma, or brain tumor, is the condition, which is very difficult to target by various anti-cancer drugs. The administration of drug through oral route may not guarantee that it will deliver most of drug to the target site. And also most of the available techniques for targeting brain tumors are either invasive or semi-invasive. Thus, it is important to deliver a drug in such a way that it can reach the target site without being invasive in nature and also improve the bioavailability with enhanced therapeutic activity. Nasal route of administration comes into play at these situations. It is one of the non-invasive techniques that can bypass the BBB. When a drug is being administered intranasally, they can enter into the brain or target site depending upon the nature of the drug, type of formulation and the physiological conditions. The different pathways of entry of drug are [54]:


Various flavonoids like curcumin [55] and rhein [56] are also been administered via intranasal delivery to study the effect of these compounds on glioblastoma, as they already possess various anti-cancer activity, anti-oxidant activity and antiinflammatory etc.

It has also mentioned in previous studies that the uses of microemulsion for the intranasal delivery are safe and effective. And moreover, since the nasal route helps in direct delivery of drug to the target site than entering into systemic circulation, the concentration of drug at the target site can be increased along with the use of microemulsion [57]. The concentration of various drugs have been improved at the target site with the help of microemulsion and some of them include albendazole sulfoxide that possess anti-proliferative activity [58] and teriflunomide that also possess anti-cancer activity [59–61].

The administration of drug through nasal route may be prone to mucociliary clearance. Thus, in this case the drug or the formulation may not be able to reach the target site and produce its therapeutic action. Thus, for this purpose, the mucoadhesive agents are being used that can slow down the mucociliary clearance [62]. Because of the enhanced penetration property of microemulsions through biological membranes, they are being used to deliver the drug through nasal cavity [63]. Thus, the use of mucoadhesive agents to the microemulsion can improve

the retention time and increase the absorption of drug. Julio Mena-Hernández et al. have formulated mebendazole microemulsion containing mucoadhesive agent namely sodium hyaluronate for intranasal delivery to target the glioblastoma. It was stated that the treatment with the formulation has increased the survival time in animals and also decreased nasal toxicity has been observed [64].
