INTRODUCTION:

Nanotechnology is a promising area in the drug delivery system and its applications to the field of medicines and pharmaceuticals has revolutionized in the twentieth century. Nanotechnology is the study of extremely small particles in nano size. The prefix “nano” is a Greek word which means “dwarf”. The word “nano” means very small or miniature size. Nanotechnology involve work from top down i.e. reducing the size of large structures to smallest structure e.g. photonics applications in nano electronics and nano engineering, top-down or the bottom up, Bottom-up, involves the assembly of nanostructures atom by atom or molecule by molecule [1].

Nanotechnology is often referred to as general purpose technology because it has significant impact on almost all industries and all areas of society. Nano science and nanotechnology are recent revolutionary development in Science and engineering that are evolving at a very fast pace [2].

What is a Nanomaterial?:

A nonmaterial is an object that has at least one dimension in the nanometer scale (approximately 1 to100 nm) [3].

Some important nano definitions:

i) Nanoscience:

Study of phenomenon and manipulation of material at atomic and molecular scale.

ii) Nanotechnology:

It’s related to design, characterization, production and applications of structure, device, and system by controlling shape and size at nanometer scale.

iii) Pharmaceutical Nanotechnology:

Embraces application of Nanoscience to a pharmacy as a nanomaterial and device like a drug delivery diagnostic imaging, and biosensor.

iv) Nanomedicine:

It is defined as a submicron size, Modules used for the treatment diagnosis, monitoring and controlling of a biological system.

Table 1: Nonmaterials are categorized according to their dimensions.

Sr. No.	Nanomaterials dimension	Example
1	All three dimensions < 100 nm	Nanoparticles, quantum dots, nanoshells, nanorings, microcapsules
2	Two dimensions < 100 nm	Nanotubes, fibres, nanowires
3	One dimension < 100 nm	Thin films, layers and coatings

Scientists have discovered that materials at small dimensions particles, thin films, etc can have significantly different properties than the same materials at larger scale. There are thus endless possibilities for improved devices, structures, and materials if we can understand these differences, and learn how to control the assembly of small structures [4].Nanotechnology is simply defined as the technology to manipulate the matter on the atomic and/or molecular scale. It is generalized to materials, devices and structures with dimensions sizes at the nanoscale of 1 to 1000 nanometers (nm) which is shown in figure 1 [5, 6].

Figure 1: Indicating nanotechnology area.

Recently Used Nano Device / Nanotechnology in the field of Pharmaceuticals:

Nanotechnology plays an important role in advancement in the development of potential site specific targeted drug delivery systems with high efficiency and low toxicities [7]. Nanotechnology is a revolution for today’s world with grateful assurances, more possibility of chances to cure the various kind of disease which is identified a major severs disease like Diabetes, cancer, cardiovascular disease. Different types of devices used, are discussed below.

1. Grapheme smart patch in diabetes:

Diabetes mellitus, commonly referred to as diabetes, is a big threat to human health globally. It is a disease characterized by high blood glucose levels (BGLs), which can cause severe damage to the eyes, kidneys, and nerves. In addition, it can also cause heart disease, strokes and even the need to remove limbs. Such complications can however be alleviated if controlled duly and effectively [8]. This disease is particularly strikes on a person who is financially well off adult. The type 2 diabetes was quickly spread to all over the world to the socioeconomic status or between the ages. For the effective treatment in type 2 diabetes disease required a patient to control their blood sugar level through the mixture of dietary restriction as well as their medication. The lots of glucose monitoring device are recently available in the market, in which user collect a small blood sample that can monitor an adequate or large amount level of sugar. To the least possible or relating the other technique that does not involve the puncturing the skin or without entering in body cavity it is possible to monitor the blood glucose level. Recently the scientist has designed a flexible glucose mongering device that suitable for skin and barely visible. This device contain array sensor that are patterned on a gold doped grapheme which are connected to gold mesh shown in figure 2.

Figure 2: Grapheme patch used to measure the glucose from sweat

How to work:

This device is activated when some amount of sweat is detected by that patch. Diabetes disease is generally associated glucose present in the blood (Blood glucose level). Several studies reveal that the blood glucose level can be estimated by the precise measurement of sweat glucose concentration. This device exhibited consistent delay between change in blood level when actually its change by sweat (Lag time).

Grapheme device contain the enzyme glucose oxidase which is further oxidized glucose and form a hydrogen peroxide during this process. The resultant hydrogen peroxide is involved in a reaction with result of electrochemical changes from which glucose and p^H sensor measurable. This path is connected to the portable analyzer which has a dual function which is power source, and wireless data transmitter. The device is user friendly, the resultant data is easily transformed on a smart phone, tablet or computers [9]. A wearable, grapheme-based patch could one day maintain healthy blood glucose levels in people by measuring the sugar in sweat and then delivering the necessary dose of a diabetes drug through the skin [10].

2. Nano film/ultra thin patches:

Polymeric ultrathin films, also called nanofilms or nanosheets, show peculiar properties making them potentially useful for several applications in biomedicine, e.g., as nanoplasters for localized drug release or as a new solution for closing endoluminal surgical wounds. In this sense, one of most challenging issues is film control in the working environment: the possibility of including magnetic components, such as magnetic Nanoparticles or nanotube, paves the way for the effective use of nanofilms in the human body, by allowing precise positioning by an external magnetic field. State of the art and new perspectives of magnetic nanofilms for biomedical applications are here presented, including fabrication, modeling, characterization and validationwhich is shown in figure 4 [11].

3. Nanotubes:

i) Carbon nanotubes:

Carbon nanotube (CNTS) is structurally different from of an element of a carbon with cylindrical nanostructure. Nanotubes have been constructed with length to diameter ratio of up to 28,000,000:1 which is significantly larger than any other materials. these cylindrical carbon having novel properties that make them potentially useful in many application in a nanotechnology, electronics, optics ,and other field of material science and architectural field. They attribute extra ordinary strength, and unique electrical properties along with efficient conductors of heat. But their final uses are mainly depends upon the potential toxicity [12].

Figure 5: Carbon nano tube along with its properties.

Nanotubes are smaller than the nonpores (figure 4). Nanotubes generally help to identify Deoxyribonucleic acid (DNA) changes which are associated with Carcinoma cell. They are nearly about half the diameter of molecule of DNA. It helps to identify a pin point’s location of the several changes. Mutated regions associated with carcinoma are firstly tagged with bulky molecule. The physical shape of DNA size quantum dots within a single bed probes can be created and further release a distinct spectrum of various colors and intensities of light serving as a sort of a spectral bar code. Latex beads filled with the crystals can be designed to bind a specific DNA sequence. When crystals are stimulated by light the colors they emit serve as dye and light up to the sequence of interest [13].

ii) Nanotube: Mapping mutation:

Once a mutation has been tagged research use a nanotube tip resembling the needle on a record player to trace the physical shape of DNA and pin point mutated region. The nanotube creates a map showing the shape of DNA molecule including the tags identifying important mutation. The location of mutation can influence the effect they have on a cell these techniques will be important for predicting disease [14].

Figure 6: Changes in DNA during mutation.

4. Nanocrystals:

Over the next decade in every different field including medicine and pharmacy nanotechnology will affect our lives tremendously. Transfer of material in to nanodimension changes their physical properties which were used in a pharmaceutics for the development of novel innovative formulations principles for poorly water soluble drugs that is the nanocrystals. Now days formulation scientists are facing most tedious challenge that of formulation of poorly water-soluble drug moieties. Advancement in high throughput screening methods is mainly responsible to an even larger number of newly discovered drugs having poor water solubility. According to literature reports, more than 40% of the drugs being introduced into the formulation research pipeline have poor water solubility. Poor water solubility of drugs translates into poor bioavailability, thereby affecting the clinical efficacy of these drugs. Strategies to improve the water solubility of these drugs are being explored in an attempt to improve their bioavailability [15, 16].

Figure 7: Structure of Nanocrystals.

Particle size reduction, particularly nanonization, is a non-specific, universal approach to improve the bioavailability of poorly soluble drugs. The decreased particle size of drug nanocrystals leads to a distinct increase in surface area. Due to the increased surface area the rate of dissolution will be proportionally raised, leading to a better absorption of the poorly soluble drug. Various technologies for the production of drug nanocrystals are known, e.g., pearl milling (Nan crystal technology, elan/Nanosystems), high pressure homogenization in water (Disso Cubes, SkyePharma) or alternatively in non-aqueous media or water-reduced media (Nanopure, PharmaSol Berlin). A first combinative technology (precipitation followed by high pressure homogenization) is known as NANOEDGETM technology (Baxter). Relatively long milling times, high numbers of homogenization cycles or solvent residues are typical drawbacks of the existing technologies. In order to overcome the limitations of the existing technologies a new combination method was developed for the production of ultra-fine submicron suspensions [17]. Drug nanocrystals are a versatile option for drug delivery purposes, and while the number of poorly soluble drug materials is all the time increasing, more research in this area is performed. Drug nanocrystals have a simple structure a solid drug core is surrounded by a layer of stabilizing agent. However, despite the considerably simple structure, the selection of an appropriate stabilizer for a certain drug can be challenging. Mostly, the stabilizer selection is based purely on the requirement of physical stability, e.g., maintaining the nano sized particle size as long as possible after the formation of drug nanocrystals [18].

5. Nanoparticles:

Nanoparticles are at the leading edge of the rapidly developing field of nanotechnology. The synthesis of Nanoparticles of specific size and composition is the burgeoning area in the nanotechnology research. Advances in the field of nanotechnology largely depend on the ability to synthesize Nanoparticles of various material sizes and shapes as well as to efficiently assemble them into complex architecture [19]. Nanoparticles can be defined as the colloidal particles (figure 8) having size ranging from 10 to 1000 nm. The advantages of nanotechnology are to provide the effective medicine (Nanomedicine) is set to substantially influence the landscape of both pharmaceutical and biotechnology industries. They have application in various fields of life sciences such as separation technologies, histological studies, clinical diagnostic assays and drug delivery systems (DDS) [20]. Silver nanocrystals, mostly hydrosols are one of the most attractive inorganic materials not only because of its tremendous applications in photography [21].

Figure 8: Structure of Silver Nanoparticles.

The silver and copper Nanoparticles are emerged as novel antimicrobial therapy to solve the problems like microbial resistance and have shown promising commercial applications [22].

6. Nano sponge emerging drug delivery system:

Targeting the delivery of drugs has long been a problem for medical researchers - how to get them to the right place in the body and how to control the release of the drug to prevent overdoses. The developments of new and complex molecules called Nanosponges have the potential to solve these problems. Nanosponges have emerged as a one of the most promising field of science because of their perceived application in a control drug delivery. Nanosponge delivery system can precisely control release rate or target drug to a specific body site and having enormous impact on the today’s health care system. This nano sized delivery system having a certain advantages for the purpose of drug delivery because of its tremendous stability, high carrier capacity and feasibility of incorporation of both hydrophilic as well as hydrophobic substance.

Figure 9: Structure of Nanosponge.

Nanosponges are a new class of materials and made of microscopic particles with few nanometers wide cavities, in which a large variety of substances can be encapsulated. These particles are capable of carrying both lipophilic and hydrophilic substances and of improving the solubility of poorly water soluble molecules [23].Nano sponge is like a three dimensional network (figure 9) structures or scaffold for a support whose backbone is a long length of polyester. It mixed in a solution with a small molecule called as a cross linkers which act as a tinny grappling hooks for fasten the different types of polymers which is together. The further effect is formed a spherically shaped particles filled with the cavities where a drug molecule is stored. The polyester is used as a biodegradable polymer [24].

7. Liposomes:

Liposome is a microscopic vesicle consisting aqueous core enclosed in a one or more phospholipids layers, used to convey vaccines, drugs, enzymes and other drug substances to target cell or organ. Liposomes are bilayered closed structure made by amphipathic phospholipid or cholesterol after hydrating in aqueous solution. Liposome’s can vary widely in size, chemical composition, and surface characteristics; they can accommodate a remarkable array of pharmacologically active substances, including antitumor and antimicrobial drugs enzymes hormones and vaccines Currently specialized liposome’s are pre pared for site-specific delivery which has led to considerable interest in the possibility of therapeutic use of liposome’s.

Liposomes are colloidal, vesicular structures composed of one or more lipid Bilayer surrounding an equal numbers of aqueous compartments (figure 10). The sphere like shell encapsulated a liquid interior which contain substances such as peptides and protein, hormones, enzymes, antibiotic, antifungal & anticancer agents [25, 26]. A free drug injected in blood stream typically achieves therapeutic level for short duration due to metabolism & excretion. Drug encapsulated by liposome achieve therapeutic level for long duration as drug must first be release from liposome before metabolism & excretion [27, 28].

The Role of Liposomal Physicochemical Properties:

Physicochemical features of liposomes have been proven to influence their efficacy in prevention and eradication of biofilms. Appropriate size, narrow size distribution, suitable Bilayer features, surface characteristics and high encapsulation efficiency are of great importance for effective antimicrobial delivery to biofilms. In addition, biofilm properties including the complex composition of extracellular matrix and physicochemical characteristics of antimicrobial agents (drugs, enzymes, metal should be considered during design of an effective liposome formulation [29].

Components of liposome’s [30]

1. Phospholipids:

2. Spingolipid

3. Sterol

4. Synthetic phospholipids.

5. Polymeric materials.

8. Denderimer:

Novel drug delivery system is to main focus on deliever the drug at a specific rate to the right direction and at a specific site of the body. A number (NDDS) are emerged for the various root of administration. Denderimer is one of the novel drug delivery system [31]. Denderimer is the new classes of polymeric materials, which is typically surrounded around the core and adopted a three dimensional, structure which provide a high degree of surface functionally and its great versatility [32]. The structure of these polymeric materials has a great impact on their physical as well as chemical properties due to their unique behavior. These are versatile well defined, physicochemical properties which resemble to the protein. Definite size denderimers has a wide range of industrial as well as biomedical application [33].

Figure 11: Basic structure of Denderimer.

There are different Denderimer families (shown in Table 2) which are applicable for different synthetic route but common in same reaction step as well as for purification [34].

Table 2: Types of Denderimer

Sr. No.	Type of Denderimer	Discovered by
1	Polyamidoamine	Tromalia
2	PAMAM (Denderimer)	Newkome
3	Arboroles	De Barbander and Meijer
4	Polypropylieneimine(PPI) Denderimer	Frechet

Pharmaceutical application of Denderimer:

1. Denderimers in pulmonary drug delivery system:

Denderimer have been reported a pulmonary drug delivery of an enoxaparin. Positively charged G2 and G3 are generated. PAMAM derivatives are responsible for increase the bioavailability by 40%.which were effective in deep thrombosis [35].

Denderimers in Oral Drug Delivery System:

This drug delivery studies using the human colon cell line, Caco2, have indicated that the low generation (PAMAM) Denderimer cross cell membranes through a combination of two processes, i.e. par cellular transport and adsorptive endocytosis. PAMAM Denderimer conjugated with the folic acid and fluorescein isothiocyanate for targeting the tumor cells and imaging respectively [36].

Denderimers as Nano-Drugs:

Denderimer poly (Lysine) modified with sulfonated naphthyl groups which have found to be useful as antiviral drugs against the simplex virus herpes, can potentially prevent/reduce transmission of HIV and other (STDs) diseases. (Poly (lysine) Denderimer with mannosyl surface groups is effective inhibitors of the adhesion of E. coli to horse blood cells in a haemagglutination assay. Hybrid of Chitosan–dendrimer has also been found to be useful as antibacterial agents [37].

Denderimers in Transdermal Drug Delivery:

Denderimers has improved solubility and plasma circulation time via transdermal formulations and to deliver drugs efficiently. Enhanced bioavailability of PAMAM Denderimer by using indomethacin as the model drug in transdermal drug application was reported to be effective [38].

CONCLUSION:

Nanoscience is truly interdisciplinary, with mutual understanding of chemistry, biological physical matter and the different process at nanoscale. It also reveals that in currently there is a great scientific disciplinary impact on physics, chemistry, Biology, as well as in a medicine and engineering. Nanotechnology is a promising area in the drug delivery system, with many possible applications of nano device. Nanomaterials are differing significantly from other materials due to their two major principal factors: the increased surface area and quantum effects. These factors can enhance properties such as reactivity, strength, electrical characteristics, and in vivo behavior. Nanotechnology is tools were collaboration between researchers in different areas has enabled the sharing of knowledge technique and tools for a different future aspect for management of diseases.

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Received on 08.02.2017 Accepted on 18.04.2017

Asian J. Pharm. Tech. 2017; 7(2): 63-71.

DOI: 10.5958/2231-5713.2017.00010.1