**7. Recent developments, significant route of administration and targeting strategies**

The route of administration of therapeutics is crucially important to cure the disease. Despite the invention of potential therapeutic moieties, the inefficient drug targeting by pills or injection on the appropriate site of the body limits therapeutics values to a larger extend. There are multiple barriers involve in the anatomical and physiological system to lack the drug efficiency, including enzymatic degradation in the stomach, absorption across the intestinal epithelium, hepatic clearance, and accumulation in non-targeted tissues. These barriers also involve a range of complexities from the tissue to the organelle level along with the time that mismatch the drug potency in vivo. Collectively, these conditions challenge the active utilization of potent therapeutic molecules for disease treatment or prevention. Extensive research has been carried out in the field of drug delivery to overcome these challenges and thus to contribute a significant role in the overall drug-development process. After the evolution of nanotechnology and vast increment in knowledge about the human body, advances have been achieved in the drug delivery field as targeted delivery and sustained/ controlled delivery system. By tuning the kinetic properties of therapeutics, the potentiality could be secured until it reaching the targeted organ and this factor is considered to be the most important in the field of pharmacology. Progresses in the nanomaterials development have been fruitful to fulfil the goals of drug delivery. Pharmacologically, the drug delivery is better explained based on the routes of drug administrations. Development of alternative drug delivery methods is crucially important to overcome the challenges experienced throughout the history of medicine. Scientists have been working on the creation of the smart drug delivery system and such approaches could provide an easy route of administration, ensuring patient compliance, decreasing toxicity, improving bioavailability and achieving precise therapeutic targeting. Creation of smart drug carrier as delivery systems and the discovery of new pharmacological compounds will potentially advance disease diagnosis and treatment beyond expectation. A variety of novel drug delivery systems have been developed using various nanomaterials during the last decade and several of them are already marketed. Nanotech‐ nology manipulates the multiple properties including the size and other physical characteris‐ tics and thus achieves both controlled and targeted delivery of drugs. The bio-adaptability and multi-functional properties of smart delivery system minimize the undesirable properties of drugs in various routes of administration, including oral, rectal, nasal, ocular, topical route such as transdermal, and dermal, parenteral route such as intravenous/intravascular, intra‐ muscular, subcutaneous, intradermal/intracutaneous, intraperitoneal and intrathecal. Figure 9 depicts the tremendous applications of new nanomaterials for the development of various routes of administration and targeting for therapeutics such as transdermal vaccine delivery, intranasal vaccine delivery and lung targeted delivery. Nasal mucosa offers numerous benefits as a target tissue for drug delivery, particularly for brain targeting because drug penetration through the BBB is favored by lipophilicity.

In particular, the non-invasive intranasal delivery offers large interests in the targeted route of administration. Nasal delivery helps drugs to bypass the blood-brain barrier and hence acts as an excellent platform for brain targeting. The intranasal drug delivery several approaches should be considered, attending, specifically, to the nature of pathological condition (acute or chronic) and intended effects of drug treatment (local, systemic or at CNS). Local delivery, nasal vaccines, systemic delivery and CNS delivery through nasal route is the prime route for drug administration to treat the various diseases. So the nasal vaccination is a promising alternative to the classic parenteral route because the nasal mucosa possesses abundant nasal associated lymphoid tissue (NALT), dentritic cells, large surface area, and low proteolytic enzymes that serve as a primary defense system against pathogens. It can exhibit high drug concentration, permeation, no first-pass effect and compliance administration without enzymatic destruction. Moreover, antigens encapsulated nanoparticles ensure enhanced uptake and controlled release of antigens from the nasal vasculature membrane with strong immunogenicity and improved systemic therapeutic responses. Also, the bio-nanotechnology applied to the parenteral administrations techniques such as microneedles, jet-injections, ultrasound, iontophoresis, and electrophoresis. Theses systems extend painless, patientfriendly alternatives to injections for the delivery of molecule [313-317]. Drug administration using microneedles for the transdermal delivery routes have been reported elsewhere [318-320]. Microneedles are arrays of micrometer-sized shallow needles that penetrate only into the superficial layers of skin, thereby eliminating the pain associated with standard

**Figure 9.** Schematic diagrams represent the recent developments of various significance routes of administration and

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targeting strategies

are multiple barriers involve in the anatomical and physiological system to lack the drug efficiency, including enzymatic degradation in the stomach, absorption across the intestinal epithelium, hepatic clearance, and accumulation in non-targeted tissues. These barriers also involve a range of complexities from the tissue to the organelle level along with the time that mismatch the drug potency in vivo. Collectively, these conditions challenge the active utilization of potent therapeutic molecules for disease treatment or prevention. Extensive research has been carried out in the field of drug delivery to overcome these challenges and thus to contribute a significant role in the overall drug-development process. After the evolution of nanotechnology and vast increment in knowledge about the human body, advances have been achieved in the drug delivery field as targeted delivery and sustained/ controlled delivery system. By tuning the kinetic properties of therapeutics, the potentiality could be secured until it reaching the targeted organ and this factor is considered to be the most important in the field of pharmacology. Progresses in the nanomaterials development have been fruitful to fulfil the goals of drug delivery. Pharmacologically, the drug delivery is better explained based on the routes of drug administrations. Development of alternative drug delivery methods is crucially important to overcome the challenges experienced throughout the history of medicine. Scientists have been working on the creation of the smart drug delivery system and such approaches could provide an easy route of administration, ensuring patient compliance, decreasing toxicity, improving bioavailability and achieving precise therapeutic targeting. Creation of smart drug carrier as delivery systems and the discovery of new pharmacological compounds will potentially advance disease diagnosis and treatment beyond expectation. A variety of novel drug delivery systems have been developed using various nanomaterials during the last decade and several of them are already marketed. Nanotech‐ nology manipulates the multiple properties including the size and other physical characteris‐ tics and thus achieves both controlled and targeted delivery of drugs. The bio-adaptability and multi-functional properties of smart delivery system minimize the undesirable properties of drugs in various routes of administration, including oral, rectal, nasal, ocular, topical route such as transdermal, and dermal, parenteral route such as intravenous/intravascular, intra‐ muscular, subcutaneous, intradermal/intracutaneous, intraperitoneal and intrathecal. Figure 9 depicts the tremendous applications of new nanomaterials for the development of various routes of administration and targeting for therapeutics such as transdermal vaccine delivery, intranasal vaccine delivery and lung targeted delivery. Nasal mucosa offers numerous benefits as a target tissue for drug delivery, particularly for brain targeting because drug penetration

In particular, the non-invasive intranasal delivery offers large interests in the targeted route of administration. Nasal delivery helps drugs to bypass the blood-brain barrier and hence acts as an excellent platform for brain targeting. The intranasal drug delivery several approaches should be considered, attending, specifically, to the nature of pathological condition (acute or chronic) and intended effects of drug treatment (local, systemic or at CNS). Local delivery, nasal vaccines, systemic delivery and CNS delivery through nasal route is the prime route for drug administration to treat the various diseases. So the nasal vaccination is a promising alternative to the classic parenteral route because the nasal mucosa possesses abundant nasal associated lymphoid tissue (NALT), dentritic cells, large surface area, and low proteolytic

through the BBB is favored by lipophilicity.

282 Application of Nanotechnology in Drug Delivery

**Figure 9.** Schematic diagrams represent the recent developments of various significance routes of administration and targeting strategies

enzymes that serve as a primary defense system against pathogens. It can exhibit high drug concentration, permeation, no first-pass effect and compliance administration without enzymatic destruction. Moreover, antigens encapsulated nanoparticles ensure enhanced uptake and controlled release of antigens from the nasal vasculature membrane with strong immunogenicity and improved systemic therapeutic responses. Also, the bio-nanotechnology applied to the parenteral administrations techniques such as microneedles, jet-injections, ultrasound, iontophoresis, and electrophoresis. Theses systems extend painless, patientfriendly alternatives to injections for the delivery of molecule [313-317]. Drug administration using microneedles for the transdermal delivery routes have been reported elsewhere [318-320]. Microneedles are arrays of micrometer-sized shallow needles that penetrate only into the superficial layers of skin, thereby eliminating the pain associated with standard hypodermic needles [321]. Microneedles have been made from a variety of materials and in particular the polymers have been shown to be effective. They have also been produced in solid and as well as in hollow forms. Solid microneedles are used to render skin permeable, whereas hollow microneedles actively deliver drugs into the skin at a controlled rate. In contrast, jet injectors deliver a high-velocity liquid jet stream into the skin, delivering drugs into various skin layers, depending on the jet parameters [322]. Jet injectors have a long history, particularly in the delivery of vaccines, insulin, and growth hormone. Ultrasound enhances skin permeability by cavitation, which temporarily disrupts skin structure [323]. Iontophoresis and electroporation use electric fields to alter the skin structure and/or provide additional driving force for drug penetration through the skin [324]. These new routes of administration of therapeutics with improved responses have been achieved by high drug concentration in target, permeation, no first-pass effect, high bioavailability and compliance administration without enzymatic destruction [325, 326].

**9. Future perspectives**

efficiency and minimize the unwanted effects.

and Sanghyo Kim1,2\*

\*Address all correspondence to: samkim@gachon.ac.kr

**Acknowledgements**

2013M3C1A8A01072922).

Seongnam-Si, Republic of Korea

**Author details**

Devasier Bennet1

Although there are considerable amount researches have been done in the field of drug delivery so far. In the polymeric nanoparticle based drug therapy has to be enhanced by incorporating by the combination therapies, Smart delivery has been achieved successful‐ ly in the case of cancer, but need to be concentrating more on other pathologies, also numerous challenges remain. From the material viewpoint, most of the smart delivery systems mechanism do well in vitro studies but flops the in vivo studies. So the research has to be re-considering to come up with simple, straightforward, efficient and reasona‐ bly accurate preparations with broadly applicable strategies, the pharmacologically active agent targeting to pathological sites, for the development of smart drug delivery systems. In technology vice the research has to focus into the fusion technologies. Although several specific specialized technologies have been shown to in polymer synthesis, functionaliza‐ tion, analysis, in vitro and in vivo study in the field of polymer science, the combinations of two or more techniques are often more effective than single technologies like a combina‐ tion of controlled radical polymerization with click chemistry. The fusion technologies can fulfil the various existing drawbacks of some individual technologies, and this has the high potentiality, synergistic enhancement in safest nanoparticle based drug delivery. Consider merging and adopting two or more right technologies for getting a high-throughput technology by selecting the right combinations is a fruitful area for research that is still largely unexplored. This new understanding must be incorporated into the future of newer polymeric based nanoparticle synthesis development and evaluation of smart drug delivery. Also the next generation of polymeric nanoparticle based delivery systems with drugs like growth factors, hormones, antibodies, genes, peptides, etc.; should also enhance the

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This work was supported by the R&D Program for Society of the National Research Founda‐ tion(NRF) funded by the Ministry of Science, ICT & Future Planning (2013M3C8A3078806 and

1 Department of Bionanotechnology, Gachon University, Bokjeong-Dong, Sujeong-Gu,

#### **8. Conclusion**

The uses of bio-nanotechnology in therapeutics a number of unexpected inventions have been done recently on polymer based nanometers, which have great attention in the field of smart drug delivery applications. The biomaterials including protein based polymers, polysacchar‐ ide based polymers, natural or synthetic or semi-synthetic polymers, various biomaterials and combination of polymer have utilized to prepare various kinds of nano-formulations towards the smart drug delivery applications. Several polymeric nanoparticle-based therapeutic systems have been established for the treatment of various diseases. Several nanoparticle based drug delivery systems have been approved in clinical trials, some of them in under pre-clinical trial levels, this nanoparticle based system can provide the increased half-life, high biocom‐ patibility, and minimum immunogenicity, site targeting and overcome the membrane barriers. Also the last era, major and new identifications have been drastically established in the smart material that alter its own structure and function in response to the environment. This performance has been used for the fabrication smart drug delivery systems, Smart polymer matrices release drugs by environment responses this system have been successfully achieved. In parallel the new method of bottom-up and top-down nanofabrication technologies provided precisely controlled size and shaped nano-particulate delivery system. Simultaneously, various advanced significant routes of targeting have developed and successfully achieved to the site of action. At present, the field of microfluidics for synthesis, micro-needle for trans‐ dermal and site targeted delivery is still in its infancy. So the pharmaceutical industry has to bring these products into industry-led investigation and the improvement in this would possibly to quicken their progress.
