**8.22 Monoclonal antibodies**

In the early 1980s two monoclonal antibodies MRK-16 and MRK-17 were discovered to alter the resistance part developed by P-gp in both *in vitro* and *in vivo* studies [75]. MRK-16 was proven with their ability to inhibit the efflux of the drugs actinomycin-D and vincristine where the MRK-17 was proven with their ability to inhibit the MDR cell proliferation. The enhancement in the anticancer activity can be achieved by conjugating the monoclonal antibodies with the P-gp inhibitors. Euhertner Roninson developed a monoclonal antibody UIC2 from the mouse which has the ability to bind with the extracellular parts of the P-gp. In turn it has the ability to decrease the efflux of P-gp substrates which in turn increases the cytotoxicity of P-gp substrates [76].

#### **8.23 Non substrate development**

The MDR in cancer cells are towards a broad spectrum of anticancer drugs, hence there is a need to develop a new anticancer drug which have less predictable by the ABC transporter family proteins. Hence a new strategy is followed where the structural modification or the conjugation is made for the discovery of the new molecule which is less familiar to the P-gp as a substrate and which are structurally similar to the compounds which act as P-gp inhibitors.

### **8.24 MDR and nanotechnology**

Nanoparticles are having a broad range of activity in the field for delivery of the anti-infective, anti-cancer and anti-inflammatory drugs. The nanoparticles are usually found in the range from 1 to 100 nm. The categories of nanoparticles include metals, solid lipid, micelles, liposome, polymers, dendrimers, and quantum dots [77–80]. The assembly of the nanoparticles are usually multilayered and the coatings of the nanoparticles are usually done to overcome the problems such as solubility, stability and specificity [81]. The issues related with the macromolecules such as low specificity, cell toxicity, high dose and cellular uptake can be limited by incorporating the drugs in the nanoparticles, even it have the ability to overcome the MDR related issues with P-gp and can enhance the therapeutic value of the parent drug [82].

#### **8.25 Liposomes**

Liposomes are extensively used for the delivery of the drugs which are impotent for the diffusion over the membrane layers. These can be modelled in phosphor lipid bi-layer and also in a micelle shapes which helps in encapsulating the soluble drugs and can hold on to their natural action. Thus nanoparticles mediate an appropriate activity in the management of MDR. For instant the activity of the Doxil encapsulated liposomal nanoparticles have the ability to manage the MDR part in the cancer cell lines [83].
