NANOTECHNOLOGY FOR DRUG DELIVERY SYSTEM

About Author:
Kambham venkateswarlu
graduate student
Sri lakshmi narasimha college of pharmacy,
palluru, chittor-517132, andhra pradesh, india
k.v.reddy9441701016@gmail.com

ABSTRACT:
Nanotechnology is the technology of nanoparticles which are made of polymers of synthetic or natural origin. Nanoparticle is a collective name for nanospheres and nanocapsules of size from 10-1000nm. Nanocapsules are vesicular systems in which drug is confined to a cavity surrounded by a unique polymer membrane. Nanospheres are matrix systems in the drug are physically and uniformly dispersed. Nanotechnology is the design, characterization, production on and application of structures, devices and systems by controlling shape and size on the nanoscale. Nanotechnology in medicine is referred to as nanomedicine and involves the implementation of technologies that exist or function at the cellular and levels medical use.

Reference Id: PHARMATUTOR-ART-1615

I.INTRODUCTION:
The method by which a drug can have a significant effect on its efficacy. Some drugs have an optimum concentration range effect on its efficacy. Some drugs have an optimum concentration range within which maximum benefit is derived. Above and below this range can be toxic or produce no therapeutic benefit at all.

On the other hand the very slow progress in the efficacy of the treatment of severe disease has suggested a growing need for a multidisciplinary approach to the delivery of therapeutics to targets in tissues. From this new idea on controlling the pharmacokinetics, pharmacodynamics, non-specific toxicity, immunogenicity, bio recognition and efficacy of drug were generated.

These new strategies after called Drug Delivery System (DDS) are based on the approaches that combine polymer science, pharmaceutics, bio conjugate chemistry and molecular biology.

To minimize drug degradation and loss to prevent harmful side effects and to increase drug bioavailability and drug targeting systems are currently under development that can control the therapies administration by means of either a physiological or chemical trigger. To achieve this goal, research is turning to advance in the worlds of micro and nanotechnology.

II.BENEFITS OF NANOTECHNOLOGY:
Due to extremely small size, nanoscale structures have technique properties for the controlled and targeted release of therapies would also reduce the severity of many side effects. Targeted implants like pharmacy chip would be occur more efficient than pills due to site specificity.
A)    Nanoscale devices should controllable release profiles especially for sensitive drugs.
B)    Microcapsules for drug delivery that have a nanoscale valve able to detect signature preteens from the cancer cells.
C)    Virus like systems for intra-cellular delivery thereby allowing drug release in different cellular components such as cytoplasm and nucleus.
D)    It is used in the development of cell and gene targeting systems.
E)     It is used in the development of universal formulation schemes that can be used as intravenous, intramuscular or peroral drug.
F)     It is used in the development of better disease markers in the terms of infinity, sensitivity and specificity.

III.NANOTECHNOLOGIES:
1. NANOWIRES
2. CANTILEVERS
3. NANOSHELLS
4. NANOPARTICLE
5. DENDIMERS
6. QUANTUM DOTS

1. Nanowires:
Nano-sized sensing wires lie across a microfluidic channel these nanoparticles by natures, have incredible properties of selectively and specificity. As particles flow through microfluidic channel, the nanowire sensor pick up the molecular signature of these particles and can immediately relay this information through a connection of electrodes to the outside world.

These nanowires are manmade constructs made with carbon silicon and other materials that have the capability to monitor the complexity of biological phenomenon. They can detect the presence of altered genes associated with cancer and may help researches pinpoint the exact location of those changes.

2. Cantilevers:
Nanoscale cantilevers – microscopic flexible beams resembling a row of dividing boards are built using semiconductor capable of binding membrane antibody.

As a cancer cell secretes its molecular products, the antibodies coated on the cantilever fingers selectively bind to these secreted proteins changing the physical properties of the cantilever and signalling the presence of cancer. Researchers can read this change in real time and provide not only information about the presence and absence but also the can of different molecular expression.

3. Nanoshells:
Nanoshells have a core of silica and a metallic outer. These nanoshells can be linked to antibodies that can recognize tumour cells (PSMA). Once the cancer cells take uo by applying a near infrared light by the nanoshells it is possible to create intense heat that selectively kills the tumour cell and not the neighboring healthy cells.

4. Nanoparticles:
Nanoparticles can be engineered to target cancer cell for use in the molecular imaging of a malignant lesion. Large number of nanoparticle are safely injected into the body and they preferentially bind to cancer cells, defining the anatomical counter of the lesion and making it visible. These nanoparticles given us the ability to see cells and molecular that we otherwise can’t be detect thought conventional imaging.

5. Dendrimers:
These are manmade polymer molecules having a tree like structure. These tree like structure with many branches allow scientists to attach a variety of molecules including drugs. They are prepared by generation in a series of controlled steps that increases the numbers of small branching molecules around a control core molecule. The first generation that is added to growing structures makes up the polyvalent surface of the dendrimer.

6. Quantum Dots:
Another minute scale molecule that will be used to detect cancer is quantum dots are tiny crystals that glow when they are stimulated by UV-light, the wavelength or colour of the light calends on the size of the crystal.

Latex beads filled with these nanoscale semiconductor dots can be designed to bind to specific DNA sequence.

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IV.EVALUATION OF NANOTECHNOLOGIES:
1. Core technology
2. Analysis of cell

1. Core technology:
Nangoen develops this technology. Nangoen’s technology utilizes the natural positive charge or negative charge of the most biological molecular, Applying an electric connect to individual test sites on the nano-chip micro array enables rapid movement and concentration of the molecular. Through electronics molecular binding on nano chip micro assay is accelerated up to 1000 times faster than traditional positive method. This technology involves electronically addressing biotinglated DNA samples, hybridizing complementary DNA reporter probes.

2. Analysis of cell:
Immunicon develops this technology it is divided into yellowing
*  Kits and marker reagents
*  Automated & standardized sample processing

V. DELIVERING OF SPECIFIC AGENTS:

1. Paclitaxel:
It is a microtubule stabilyzing agent which promotes polymerization of tubulin causing cell death by disrupting the dynamics necessary for cell division bridgeable nanoparticle formulation using poly-lactic-co-glycolic acid have shown comparable activity to traditional formulation and much faster administration. Paclitaxel could be incorporated at very high loading efficiencies nearing 100% using the nanoprecipitation method using Acetone and PLGA.

2. S-Fluorouracil:
Incorporation of S-Fluorail has also been achieved using dendrimers of poly (amidoamive) modified with MPEG-500. The hydrophilicity SFU allowed it to complex with dendrimers after simply incubating the polymer with the drug.

3. Anti Neoplastic agents:
Camptotesin based drug, specifically Iridotecan (camptrar) and Topofecan (Hycampting) have been approved by the FDA and are used in conjunction with FDA as a first nanoparticle of 3100-375 nm diameter were prepared with the SM-38 analogue of Iriotecon in lipid based nanoparticles.

VI.POTENTIAL RISK OF NANOTECHNOLOGY:
These are brosdly divided into three areas:
*  The risk to health and environment from nanoparticles and nanomaterials.
*  The risk possessed by molecular manufacturing or advanced nanotechnology.
*  Societal risk.

1. Risk from nanoparticles:
The mere presence of nanomaterials is not in itself a threat. It is only certain aspects that can make them risk in laity and in art C for their mob an their increased relatively only if certain properties of certain nanoparticles were harmful to living beings or the environment would be faced with a genuine hazard.

2. Health Issues:
·         Within the body nanoparticles are highly mobile and in some instances can even across the blood brain barrier.
·         Basically the behaviour of nanoparticles is a function of their size, shape and surface reactivity with the surrounding tissue they could cause “overload” on phagocytes there by triggering stress reactions that lead to inflammation and weaken the bodies against other pathogens.

3. Risks from molecular manufacturing:
As after site worst case scenario is “grey goo” a hypothetical substance into which the surface of the earth might be transformed by self replicating nanorobots.

-  With the advent nanobiotech a different scenario called green goo has been forwarded. Here, the malignant substance is not nanorobots but rather self replicating organisms engineered through nanotechnology.

4. Societal Risks:
Societal risks from the use of nanotechnology have also been raised.

On the structural level, critics of nanotechnology point to a new world of ownership and corporate control opened up by nanotechnology.

5. Nanotechnology risk and Regulatory:
Regulatory bodies such as the environmental protection agency and regulatory the FDA in the US or the health and consumer protection directorate of the European Commissions has started dealing with the potential risks posed by nanoparticles. But current risk assessment methodologies are not suited to the hazards to associate with nanoparticles in particular existing toxicological and eco-toxicological methods are not up to the risk.

Regulatory bodies in the US as well as in the EU have concluded that nanoparticles from the potential at for an entirely new risk and that are necessary to carry extensive analysis of the risk. The outcomes of these studies can their form the basis for governmental, international regulations.

VII. THERAPEUTIC APPLICATIONS OF NANOPARTICLES:

1. Intracellular Targeting:
*  The ned for antibiotic with greater intracellular efficacy led to the development of endocytosable drug carriers including nanoparticles, which mimics the entry path of the bacteria by penetrating the cells into phagosomes and lysosomes.

a)      The therapeutic index of Ampicillin for liver bacterial counts rise at least 20 fled after its linkages to ploy hexyl cyanoacryllate (PIHCA) nanoparticles.

b)      Nifurtimox and Allopurinol loaded ploy ethyl cyanoacryllate nanoparticles as potential lysosomotropic carrier for thr trypanocidal activity against trypanosome Cruzi which is responsible for chagas disease.

2. Nanoparticles in chemotherapy:
Nanoparticles loaded drugs have resulted in the effective treatment of a number of chemotherapy refractory cancers both in animal and clinical models.

Eg:

A) Enhanced cellular accumulation of Doxorubicin following the administration of polyisohexylcyanoacrylate nanoparticle bound doxorubicin (as compared to free drug) in multi drug resistance tumour cell line.

3. Adjuvant effect for Vaccines:
The adjuvant effect of nanoparticles could be ascribed to the sustained release of the entrapped antigen or improved uptake and subsequent processing of the nanoparticles bound antigen by the immune system of the body.

Eg:

Polymethyl methacrylate, nanoparticles containing the Ifluenza antigen induced significant antibody response against Influenza virus to a great extent the antigen alone.

A) When poly methyl methacrylate, nanoparticles were used as adjuvants for HIV-2 dhows excellent adjuvanticity as compared to Aluminium Hydroxide or an aq.control solution.

4. Nanoparticles for administration of proteins and peptides:
Nanoparticles have been employed as peroral drug carriers with the following objectives.
*  Improvement of the bioavailability of drugs with poor absorption characteristics.
*  Delivery of vaccine antigens to the get associated lymphoid tissue (GALT)
*  Controlled or sustained release of the drug.
*  Assurance of the stability of drugs in the GIT.

Eg;

A) PACA nanoparticles wre also proposed as possible as drug delivery systems for cyclosporine A having a specific immune Suppressive activity.

B) nanoparticles of RIGA loaded with Amphotericin B delivery with better therapeutic index and low incidence of toxic manifestations.

5. Nanoparticles for intra-arterial applications:
Nanoparticles could prove to be effective dosage form forn an intra-arterial localization of therapeutic agents forn preventing restenosis. Nanoparticles are putative drug carriers for the treatment of Restenosis as they localize the therapeutic agents at the site of artery injuring rather than systemic administration.

Eg;

Nanoparticles facilitate the local delivery of drug like Dexamethasene, Heparin and U 86983 with high regional concentration and prolong retention in lower doses and reduced systemic toxicity.

6. Nanoparticles for brain delivery:
Delivery of the brain using nanoparticles results in
*  Higher concentration gradient at the blood brain carrier that may enhance the transport across the endothelial cell layer and hence increased retention in the brain.
*  Endocytosis of nanoparticles by the endothelial cells followd by the release of the drug intracellular.

Eg;

A)    Drug that have been used for brain targeting using nanoparticles included Flexapeptide dalargin, loperamide, Tubocurarine and Doxorubicin.

8. Nanoparticles for DNA delivery:
Nanoparticles have been recently used as a delivery vehicle for the transfection of pDNA and to improve their stability in the bio environment.

A)    Nano size range (600 mm) pDNA- loaded in poly (DL-lactide co-alveoli de) polymer particles with high encapsulation efficiency exhibited sustained release of pDNA a month.

B)    Nanosphere-DNA incubated in bovine serum was more resistant to nuclease digestion compared to naked DNA.

9. Nanoparticles for oligonucleotide delivery;
Anti sense oligonucleotides (ODNS) are used in treating human immunodeficiency virus infection, hepatitis B virus infection, Herpes simpleton virus infection, cancer restenosis, rheumatoid Arthritis and allergic disorder.

Eg;

Oligonucleotides adsorbed onto polyalkyl cyano acrylate nanoparticles enhance stability against reeases and more ideal calculated disposition.

10. Nanoparticles for lymph targeting:
The major purpose of lymph targeting is to provide an effective anticancer chemotherapy to prevent the metastasis of turnout’s cells by accumulating the drug in the regional lymph node via substances administration.

A wide range of studies are out of date for the lymphatic targeting using nanoparticles as drug carriers.

A)    P61 – alkyl-cyanoacrylate nanoparticles bearing drugs or tumour of peritoneal cavity.

B)    Polyisobutyl cyanoarylate nanoparticles loaded with insulin for peroral peptide delivery through payer’s patches

C)    Magnetite dextrin nanoparticles as a contracts agent in magnetic resonance imaging.

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VIII. DRUG DELIVERY SYSTEMS
Summary of application areas for nanoscale pharmaceuticals and medicine in drug delivery.

IX. TISSUE REGENERATION, GROWTH AND REPAIR
Summary of application areas for nanoscale pharmaceuticals and medicine in tissue regeneration, growth and repair

X. MARKETS FOR NANOTECHNOLOGY DERIVED DRUG DELIVERY SYSTEMS:
At present there are 30 main drug delivery products in the market. The total annual income for all these is approximately US$33 billion with an annual growth of 15% (based on global product revenue).

XI. NANOPARTICULATE DRUG APPROVED:
1. Ambraxane is the first polymeric nanoparticle based product from American Pharmaceutical partners, Inc., and American Bioscience, Inc (ABI). It was approved in year 2005 and is consisting of albumin boumd paclitaxelnanoparticles. This product is free of toxic solvents like cremophor-EL which solubilze paclitaxel in order to administer it intravenously to the patient. Cremophor-EL is known to cause life threatening allergic reactions.

2. Tracer R (Fenfibrate) was launched in December 2004 by Abbott in the US following FDA approval. The new formulation of Tracer provides the benefits of a simplified, flexible dosing regimen and allows for administration with or without food. The old formulation had to be taken with a meal.

XII. CONCLUSION:
Nanoparticles provide massive advantages regarding drug targeting, delivery and release and with their potential to combine diagnosis and therapy, emerge as one of the major tools in nanomedicine. The main goals are to improve their stability in the biological barriers. The cytotoxicity of nanoparticles or their degradation products remains a major problem and improvements in biocompatibility obviously are a major of future research.

Although Biotechnology at the scale reveals new moral, ethical, and legal quantities, learning from our history with other technologies may hopefully allow us to eliminate, or at least mitigate, some of the potential problems of monomaniacal technology. If we can do this, nanomedicine may prove to be a tremendous asset to humanity.

XIII.REFERENCES:
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