**9. A glimpse to future of nanosize drug delivery systems**

binds with receptor EGFR. Also mixing cationic lipids with plasmid DNA leads to the formation of lipoplexes where the process is driven by electrostatic interactions [66]. The negatively charged genetic material (e.g. plasmid) is not encapsulated in nanoliposomes but complexed with cationic lipids by electrostatic interactions. Plasmid liposome complexes can enter the disease cells by infusion with the plasma or endosome membrane. Allovectin-7 (gene transfer product) is composed of a plasmid containing the gene for the major histocompatibility complex antigene HLA-B7 with B2 microglobulin formulated with the cytofectin [67]. The nature of a composed lipid decides the unloading of the gene from nanoliposomes which enables control over the mode of release, doping of nanoliposomes with neutral lipids such as 1,2-Dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) which helps in endosomal mem‐ brane fusion by recognizing and destabilizing the phospholipids in a flip flop manner which paves way for the liposomes to integrate in the membrane with the dissociation of nucleic acid

Viral system based gene carrier had the ability to overcome the biological barriers in the body and then access to the host nucleus replicative machinery which resulted in the exploitations of the system for drug delivery using nanotechnology [64]. The develop‐ ment of a non-viral method for *in vivo* gene transfer was designed where the vector was packed into compact nanoparticles by successive additions of oppositely charged polyelec‐ trolytes including an incorporation of ligands into the DNA-polyelectrolyte shells which were mixed with Pluronic F127 gel serving as a biodegradable adhesive to keep shells in

A novel method of gene delivery is with viruses such as adeno associated virus (AAV) which have their virulent genes removed with lentiviruses, clearly showing their efficiency [64].

The viral nanoparticles (VNPs) consist of protein core which ranges in complexity from small capsid-protein homomers to larger protein-based heteromers capable of internalizing oligo‐ nucleotides and being enveloped by lipids. Chemical modification process and genetic mutation provide the viral coat proteins with receptor binding domain that helps in cell specific targeting of VNPs [69]. Even fusion of terminal / internal proteins on the surface or inside the VNPs can be utilized for introduction of heterologous peptides, and in some cases entire proteins. VNPs can be genetically engineered by inserting amino acids for bioconjugation, peptide based affinity tags and peptides as targeting ligands for stimulation of immune

High sequence variability due to the influence of the immune system in viral life-cycles is often seen on the surface loops of viral capsid proteins. This variability makes the loops highly susceptible to insertion of foreign sequences. VP1, the major coat protein of viruses of Polyo‐ maviridae family, when expressed in insect cells, yeast and *Escherichia coli* self-assembles as protein cages and shows natural affinity for a cell surface glycoprotein with a terminal a 2,3 linked N-acetylneuraminic acid and attaches to a4h1-integrin receptors [71]. Virus like particle

**8. Drug delivery with the help of empty virus capsid**

into the cytoplasm [64].

536 Application of Nanotechnology in Drug Delivery

response. [70].

contact with the targeted vessel [68].

Advancement of nanosize drug delivery systems establishes a new paradigm in pharmaceut‐ ical field. Convergence of science and engineering leads a new era of hope where medicines will act with increase efficacy, high bioavailability and less toxicity. Several nanoscale drug delivery systems are currently in clinical trials and few of them are already commercially available. Examples of such products are Abeicet (for fungal infection), Doxil (antineoplastic), Abraxane (metastatic breast cancer), Emend (antiemetic) etc. Despite the impressive progress in the field, very few nanoformulations have been approved by US-FDA (United States Food and Drug Administration) and even reached market in recent years. Although nanocarriers have lots of advantages because of the unique properties they have, there are many clinical, toxicological and regulatory aspects which are the matters of concern too. The biocompatibility of nanomaterials is of atmost importance because of the effect of the nanomaterials in the body ranging from cytotoxicity to hypersensitivity [8]. With the advancement of nanotechnology, the biological phenomenon such as host response to a specific nanomaterial should also be clinically transparent [9]. Therefore it is quite essential to introduce cost effective, better and safer nanobiomaterials which will provide efficient drug loading and controlled drug release of some challenging drug moieties for which there is no other suitable delivery available yet.

Nanoliposomes are well developed and presently possess the highest amount of clinical trials among other nanomaterials with some formulations currently in the market. This may be due to the fact that other materials have not been investigated for the same duration and are relatively newer in comparison. However polymer based nanomaterial, carbon nanotubes, gold nanoparticles etc. should not be overlooked because of less number of clinical trials [7].

Genexol-PM is an example which was undergone recent clinical trial. This is an amphiphilic diblock co-polymer (PEG-D, L-Lactic acid) that delivers paclitaxel. Clinical trial currently is in phase IV using Genexol-PM for recurrent breast cancer and phase III for breast cancer. Fungal infections associated with acute leukemia and for central line fungal infections, amphotericin B containing nanoliposomes are in phase IV clinical trial. ThermoDox (Doxorubicin loaded nanoliposome) is currently in phase III trials for hepatocellular carcinoma. Similarly Caelyx, a doxorubicin HCl loaded nanoliposome that is pegylated, is currently in phase IV trials for ovarian neoplasms [7]. Some recent clinical trials are shown in Table 1.

Ligand or antibody conjugated nanoformulation, bifunctional and multifunctional nanopar‐ ticles are the newer research approaches through which detection and treatment of cancerous cells can be achieved. Nanomachines are also largely in the research-and-development phase, but some primitive molecular machines have been tested. An example is nanorobot which is capable of penetrating the various biological barriers of human body to identify the cancer cells. Thus, nanodrug delivery systems have a leading role to play in nanomedicine in near future.

The global importance of trade for nanomaterials has established new international organiza‐ tions, such as the International Council on Nanotechnology (ICON), the International Organ‐ ization for Standardization (Geneva, Switzerland) etc. for sharing responsibilities in this field. In the year 1996 the NNI was established in the United States of America to coordinate governmental multi-agencies such as the Food and Drug Administration (FDA), the Depart‐ ment of Labor through the Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), and the Environmental

Current Status and Future Scope for Nanomaterials in Drug Delivery

http://dx.doi.org/10.5772/58450

539

Last few years several new technologies have been developed for the treatment of various diseases. The use of nanotechnology in developing nanocarriers for drug delivery is bringing lots of hope and enthusiasm in the field of drug delivery research. Nanoscale drug delivery devices present some advantages which show higher intracellular uptake than the other conventional form of drug delivery systems. Nanocarriers can be conjugated with a ligand such as antibody to favor a targeted therapeutic approach. The empty virus capsids are also being tried to use for delivering drugs as a new therapeutic strategy. Thus, nanoscale size drug delivery systems may revolutionize the entire drug therapy strategy and bring it to a new height in near future. However, toxicity concerns of the nanosize formulations should not be ignored. Full proof methods should be established to evaluate both the short-term and long-

, Niladri Shekhar Dey, Ruma Maji, Priyanka Bhowmik,

[1] Ochekpe NA, Olorunfemi PO, Ngwuluka NC. Nanotechnology and drug delivery part 1: background and applications. Trop J Pharm Res. 2009; 8(3): 265-274.

[2] Commission Staff Working Paper. Types and uses of nanomaterials including safety aspects accompanying the communication from the commission to the European

Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India

Protection Agency (EPA), for the development of nanoscience and technology.

term toxicity analysis of the nanosize drug delivery systems.

\*Address all correspondence to: biswajit55@yahoo.com

**10. Conclusion**

**Author details**

Biswajit Mukherjee\*

**References**

Pranab Jyoti Das and Paramita Paul


Abbreviations: PEG-Polyethylene glycol, TNF-Tumor necrosis factor, NCI-National Cancer Institute, AuNP-Gold nanoparticles

**Table 1.** Recent Nanodrug Carriers in Clinical Trials (Source: Clinicaltrials.gov)

Nanocarriers may lead to a solution to major unsolved medical problems which will aggres‐ sively enhance quality of life.

**Regulatory aspect:** One of the main areas related to the safety aspects of drug-nanocarrier systems is to encourage academic organizations, industry and regulatory governmental agencies to establish convincing testing procedures on the safety aspects of the nanomaterials. The global importance of trade for nanomaterials has established new international organiza‐ tions, such as the International Council on Nanotechnology (ICON), the International Organ‐ ization for Standardization (Geneva, Switzerland) etc. for sharing responsibilities in this field. In the year 1996 the NNI was established in the United States of America to coordinate governmental multi-agencies such as the Food and Drug Administration (FDA), the Depart‐ ment of Labor through the Occupational Safety and Health Administration (OSHA), the National Institute for Occupational Safety and Health (NIOSH), and the Environmental Protection Agency (EPA), for the development of nanoscience and technology.
