NANOPHARMACEUTICALS

~Dr Sagarika Barman , Dr Chukham Gohain  , Dr Dibakar Baruah 

     Today, antibiotics, probiotics and pharmaceuticals are delivered to animals primarily through feed or injection systems. Nano scale devices are envisioned that will have the capability to detect and treat an infection, nutrient deficiency, or other health problem, long before symptoms are evident at the macro-scale. This type of treatment could be targeted to the affected area. ‘Smart’ delivery systems.

1) NANO ANTIMICROBIALS:

One of the areas of veterinary medicine that would benefit most from the nanotechnology research is the field of pharmacology (1). In chronic intra cellular infection cases pathogen can survive inside the cells from months to years. Which leads to low activity of antimicrobial inside the cell. Antimicrobial toxicity to healthy tissues poses a significant limitation to their use. In other hand Nano antimicrobial enhances therapeutic effectiveness and minimize undesirable side effects of the drugs. The creation and manipulation of new synthetic molecules can provide us with new therapeutically compounds to treat diseases in our pet population. These new compounds for example would protect animals from viral or bacterial infections and accelerate wound healing (2). A chemotherapeutic agent when is encapsulated in the nano particle may cause less toxicity and cellular resistance to the drug compared to traditional chemotherapy medicines. As example, doxorubicin and paclitaxel are very effective in the treatment of ovarian carcinomas when used together, but they present high toxicity. A study using structured lipid nano particles of both actives against multi drug-resistant cancer cell lines demonstrated that the nanoparticles were highly effective in controlling tumor cell growth and caused less toxicity in cells (3). The use of nanotechnology in active antimicrobial has also shown satisfactory results. Penicillin is the first and most ancient antimicrobial agent from the group of β-lactams, which has been used for decades in the treatment of bacterial infections. However, indiscriminate use resulted in the selection methicillin resistant Staphylococcus aureus (MRSA) strains. A study allowed the covalent attachment of a chain of penicillin polyacrylate nanoparticle structure with approximately 100nm. The researchers compared the in vitro activity of nanostructured molecule with a conventional formulation. In MRSA strains, nanostructured formulation is more effective, which was attributed to a probable active protection against action of bacterial β-lactamases and / or protection against penicillin binding proteins (4). Escherichia coli and Salmonella typhi bacteria are two common pollutants and they are developing resistance to some of the most used bactericide. Therefore new biocide materials are being tested. Thus, gold nano particles are proposed to inhibit the growth of these two microorganisms. Gold nano particles dispersed on zeolites eliminate Escherichia coli and Salmonella typhi at short times. The biocidal properties of gold nano particles are influenced by the type of support which, indeed, drives key parameters as the size and roughness of nano particles. These materials contained particles sized 5 nm at surface and eliminate 90–95% of Escherichia coli and Salmonella typhi colonies (5).

2) ANTICANCER NANODRUGS:

 Cancer is one of the leading causes of death worldwide, occupying the second place in developing countries, and showing a growing incidence over time (6). In cancer, there is a small subset of cancer cells-cancer stem cells (CSC)-that, like normal stem cells, can self-renew, give rise to heterogeneous populations of daughter cells, and proliferate extensively (7). Standard chemotherapy is directed against rapidly dividing cells, the bulk of non-stem cells of a tumor, and thus CSC often appear relatively refractory to those agents (7). The development of side effects in normal tissues (e.g. nephrotoxicity, neurotoxicity, cardio toxicity, etc.) and multidrug resistance (MDR) mechanisms by cancer cells leads to a reduction in drug concentration at target location, a poor accumulation in the tumor with consequent reduction of efficacy that may associate to patient relapse (8). Targeted drug delivery using nanotechnology can open a new era of cancer therapy. It direct the specific anti-cancer drugs to the cancer area. It can also visualize & evaluate circulating cancer cells in faster rate by combinatorial use of MRI and QDs.

 

 

TARGETED CANCER THERAPY

The objective of TCT is to deliver chemotherapeutic directly to the cancer tissue and minimizing undesirable toxicity to the rest of the body.

Nanoparticle Formulation:

Nanoparticle formulation begins with the solution of drugs and polymer molecules in an organic solvent. This nanoparticles are composed of diblock co-polymer, which are very flexible in nature. Diblock co-polymer is composed of two joint polymer chain (one hydrophilic & one hydrophobic). Nanoparticles formation is accomplished by the addition of organic solution to rapidly stirring water. Because of which the initially disorder co-polymer rapidly self-assemble  and reoriented themselves in such a way that Hydrophobic blocks stabilized by the hydrophilic blocks. These polymer coating can be subsequently surface modified by various cancer targeting ligands i.e. antibodies or small molecules.

Delivery of nanoparticles:

The nano particle solution then can be introduced to the body by I/V administration. By which it quickly get distributed throughout the body by the circulatory system (also deliver to the site of the cancer). Because of their small size nano particles possess the unique ability to permeate through the wall of tumor vasculature. Through this passive targeting technique the nano particles can be concentrating with in the tumor tissue.

Targeted cellular uptake:

On the cancer cells, surface membrane the nano particles encounter surface receptor molecules or oncoreceptors, microscopic markers molecules express on cancer cells and not express by normal tissue. The nano particles targeting ligands binds specifically to these receptors, triggering a response also known as “receptor mediated endocytosis”, which draws the nano particles in to the cancer cells this process enable thousands of nanoparticles to enter in to each of the cancer cells. Inside the cell the nano particles are engulfed in an endosomes. These endosomes merge to form larger endosomes and eventually form lysosome, the digestive stomach of the cell. Anticancer drugs release in controlled manner by the degradation of polymer nanoparticle shell. Highly toxic chemotherapy can thus be delivering directly on the site without affecting other body system. Typically the drug will cause the cancer cells to undergo apoptosis or programmed cell death. These nanoparticle therapy can eventually leads to eradication of tumor.

Nano shell as cancer therapy:

 Nano shells can carry molecular conjugates to the antigens that are expressed on cancer cells or in the tumor micro environment. This second degree of specificity preferentially links the nano shells to the tumor and not to neighboring healthy cells. It is then possible to externally supply energy to these cells. The specific properties of nano shells allow for the absorption of this directed energy, creating an intense heat that selectively kills tumor cells. The external energy can be mechanical, radio frequency or optical – the therapeutic action is the same (9).

 

1) Feneque, J. (2000). Nanotechnology: a new challenge for veterinary medicine.The Pet Tribune.6 (5): 16.

2) Vikrama Chakravarthi. P and Sri N. Balaji. Applications of Nanotechnology in Veterinary Medicine. Veterinary World, 2010, Vol.3(10):477-480.

3) DONG, X.; MATTINGLY, C.A.; TSENG, M.T.; CHO M.J., LIU, Y.; ADAMS, V.R. et al. Doxorubicin and Paclitaxel-Loaded Lipid-Based Nanoparticles Overcome Multidrug Resistance by Inhibiting P-Glycoprotein and Depleting ATP. Cancer Res., v.69, n.9, p.3918-3926, 2009.

4) TUROS, E.; REDDY, G.S.K.; GREENHALGH, K.; RAMARAJU, P.; ABEYLATH, S.C.; JANG, S.; DICKEYC, S.; LIMC, D.V. Penicillin-bound polyacrylate nanoparticles: Restoring the activity of b-lactam antibiotics against MRSA. Bioorg. Med. Chem. Letters, v.17, p.3468–3472, 2007

5) LIMA, E.; GUERRA, R.; LARAAND, V.; GUZMÁN, A. Gold nanoparticles as efficient antimicrobial agents for Escherichia coli and Salmonella typhi. Chemistry Central Journal, v.7, p.11, 2013.

6) Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA: A Cancer Journal for Clinicians 2011;61(2): 69-90.

7) Clarke MF, Dick JE, Dirks PB, Eaves CJ, Jamieson CHM, Jones DL, Visvader J, Weissman IL, Wahl GM. Cancer Stem Cells-Perspectives on Current Status and Future Directions: AACR Workshop on Cancer Stem Cells. Cancer Research 2006;66(19):9339-9344

8) Joana Silva, Alexandra R. Fernandes and Pedro V. Baptista. Application of Nanotechnology in Drug Delivery.//dx.doi.org/10.5772/58424. pp: 127.

9)Hirsch L.R., Stafford R.J., Bankson J.A., Sershen S.R., Rivera B., Price R.E., Hazle J.D., Halas N.J. & West J.L. (2003). – Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance. Proc. natl Acad. Sci. USA, 100 (23), 13549-13554.

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Authors – Dr Sagarika Barman 1 , Dr Chukham Gohain 2 , Dr Dibakar Baruah 3

  1. Research Fellow, College of Veterinary scienceBlock
  2. Veterinary Officer, NagaonBlock
  3. Veterinary Officer, Demow, Sivasagar

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