**2.1 Liposome-based nanomedicines**

Liposome-based nanomedicine is a type of drug formulation where a drug is encapsulated inside the phospholipid bilayer structure to enhance its bioavailability and therapeutic activity. Liposome formulations are one of the oldest nanomedicines with a well-established technique. Many research efforts were focused on using liposomes to encapsulate several cargos like small molecules such as doxorubicin, nucleic acid such as RNAs, and biological molecules such as vaccines for hepatitis A virus. Furthermore, administration of the liposomes without an encapsulated drug is also a possibility if the liposome subunits have a certain therapeutic effect such as sphingomyelin and cholesterol. PEGylation is an option to consider while using liposomes due to its importance in adding stealth to the delivery system. Most of the approved liposome-based nanomedicines are used for the treatment of cancer diseases. They take a large place in research as 10 out of the 29 approved nanomedicines are liposome-based.

#### **Figure 4.**

*Clinically approved and investigated nanomedicines including organic nanoparticles and inorganic nanoparticles.*

## **2.2 Lipid-based nanomedicines**

Lipid nanosystems including nanoemulsions and solid lipid-based nanoparticles are another form of nanomedicine, which are usually used to encapsulate hydrophobic cargos to improve permeation and control release profile. Usually, a surfactant is used to ensure a uniform dispersion. Lipid nanomedicine can also encapsulate some gene therapeutics such as siRNA or contrast agents used for imaging such as F-butane. Generally, lipid nanomedicine can improve the pharmacological effect by enhancing drug accumulation in targeted tissues beside its biocompatibility. However, there are several drawbacks like rapid clearance due to reticuloendothelial system (RES) uptake and some limitations for administration routes and challenges regarding system stability [5, 6]. Unlike liposomal-based nanomedicines, lipid-based nanomedicines are not limited for cancer diseases only. Some of the diseases that are treated by lipid-based nanomedicines are amyloidosis, hepatitis B, and hepatic fibrosis. Furthermore, several types of nanoemulsion were loaded with drugs like simvastatin, cinnarizine, coenzyme Q10, and cyclosporine, which used as antihyperlipidemia, antihistaminic, antioxidant, and immunosuppressants, respectively.

### **2.3 Albumin-based nanomedicines**

Albumin-based nanomedicines are another form of nanosystems, where albumin, especially human serum albumin (protein), is used as a carrier. Albumin nanosystems can be loaded with different cargos via a simple self-assembly procedure of albumin in aqueous solution with simple crosslinking step. The main advantage of albumin is biocompatibility. Despite that, only 2 out of the 29 listed approved nanomedicines and 2 out of the 65 nanomedicines under clinical trials are albumin-based. It is currently used in imaging and delivering drugs that treat cancer diseases.

#### **2.4 Micelle-based nanomedicines**

Micelles are self-assembled nanosystem by amphiphilic molecules that have a hydrophilic part and a hydrophobic one. They have several advantages like high permeability and solubility, which improve drug bioavailability. However, they still have some drawbacks like insufficient control to drug release and cytotoxicity due to amphiphilic molecule use, which interact with cell membrane [5, 7]. Although several reports used block copolymeric micelles to reduce clearance and increase bioavailability of chemotherapeutic agents and other types of drugs, there are no approved micelle-based nanomedicines. However, there are currently nine micellebased nanomedicines undergoing clinical trials. Majority of them are used for cancer treatment.

#### **2.5 Polymeric-based nanomedicines**

Polymeric nanoparticles are one of the most commonly used nanosystems for drug delivery. Several polymers have been used like ethyl cellulose, poly(lacticco-glycolic acid), polylactic acid, cyclodextrin, alginate, and chitosan. Depending on the nature of the polymer, either hydrophilic or hydrophobic, there are several techniques that have been used to prepare polymeric nanoparticles. Several advantages like relative stability and prolonged duration of action make polymeric nanoparticles a promising platform for the market. However, there are no marketed products based on polymeric nanoparticles. Only three products are currently on clinical trials for cancer.

**7**

*Introductory Chapter: Overview on Nanomedicine Market*

are currently on clinical trials for treating cancer.

**3. Nanomedicines pharmacokinetic and regulations**

Inorganic-based nanomedicines have several subtypes. Due to degradability and biocompatibility issues, few types have been used for therapeutic purpose, while other types for diagnostic purpose like imaging agents. One of these subtypes are metal oxide nanoparticles such as hafnium oxide nanoparticles which enhance tumor cell death via electron production through their stimulation with external radiation. Another subtype is in the form of colloids such as iron dextran colloids, iron gluconate colloid, and other similar derivatives that are usually used for the treatment of iron-deficiency anemia. The last subtype mentioned is iron−/silica−/ gold-based nanomedicines, either as nanoparticles with drugs arranged on the surface for the treatment of cancer or as nanoshells/nanoparticles used for thermal ablation of tumors. There are 12 products in the market that belong to this type. Eight products used iron-replacement therapies. On the other hand, four products

The pharmacokinetic parameters of nanomedicines are similar to free drugs with addition phase after drug administration, which is the liberation phase beside the standard absorption, distribution, metabolism, and excretion (ADME). This new phase is controlled by particle nature, size, shape, and surface properties. It is worth to mention that particle size is very important for absorption and elimination. Particles with particle size <5 nm is easily excreted from the kidney, while larger particle size could be eliminated by the liver or engulfed by mononuclear-phagocyte

system. Moreover, particle size and shape can affect particle accumulation in targeted tissues like ellipsoidal shape that has better distribution and retention in tumor tissue than spherical one. Surface modification of nanoparticles can affect particle uptake and elimination. Many nanoparticles are coated for active and passive targeting. Passive targeting is a non-specific retention in target tissue like solid cancer tissue by enhanced permeability and retention mechanism. Active targeting is the selective uptake of nanomedicine by specific cells. Target moieties could be protein, antibody, or small molecule selective to specific tissues or cells. This mecha-

nism is mainly controlled by homing to overexpressed cell surface receptors. The Food and Drug Administration classified nanoscale materials to nanomaterials as "materials used in the manufacture of nanomedicine" or nanomedicine as "final products," The FDA approved 51 nanomedicines by the year 2016, 40% of which were in clinical trials between 2014 and 2016. According to the FDA evaluation of nanomedicines, it includes the physicochemical properties, followed by pharmacokinetics evaluation of nanomedicines. The pharmacokinetics evaluation includes (1) rate and amount of absorption, (2) retention in circulation, (3) half-life and complete elimination, (4) bioavailability differences, (5) distribution or accumulation to the body or specific tissue for active targeting, (6) decomposition or metabolism, (7) elimination, and (8) toxicity assessment of nanomedicines. On the other hand, the European Medicines Agency defined nanomedicines as "drugs composed of nanomaterials 1–100 nm in size, and these are classified into liposomes, nanoparticles, magnetic nanoparticles, gold NPs, quantum dots, dendrimers, polymeric micelles, viral and non-viral vectors, carbon nanotubes, and fullerenes." EMA has approved eight commercially available nanomedicines as first-generation nanomedicines. Currently, there are 48 nanomedicines in clinical trials (Phases 1–3) in the EU. EMA evaluates the pharmacokinetics and pharmacodynamics of nanomedicines through investigation of their chemical composition and physicochemical properties [8].

*DOI: http://dx.doi.org/10.5772/intechopen.91890*

**2.6 Inorganic-based nanomedicines**
