CSIR Makes Headway in Nanotechnology:Gold Nanoparticles for Novel Drug Delivery

CSIR Makes Headway in Nanotechnology –

Gold Nanoparticles for Novel Drug Delivery

 {Feature has been uploaded by CSIR (Unit for Science Dissemination), Ministry of Science & Technology, New Delhi}

Enter the world of fantasy – the realm of nanoworld – and you will find structures with dimensions about the size of atoms, which are the building blocks of all matter existing in Nature. The study and design of such structures, measuring in the scale of nanometre or one-billionth of a metre is what nanotechnology is all about. The sheer size of nanostructures is the hallmark of the astounding applications of nanotechnology in diverse fields.

            In the field of Medicine, the unimaginably vast potential of nanotechnology has opened up the possibility of designing nanostructures for both diagnosing the diseased tissues and delivering drugs and other therapeutic substances to target areas in the human body. It is a matter of pride that CSIR scientists have made a significant headway in designing nanoparticles of gold for delivering drugs to specific body cells. Interestingly, these nanoparticles are covered with stabilizing agents that prevent their aggregation and also help the nanoparticles survive in both alkaline and acid media. Gold is chosen for designing these nanoparticles primarily because of its non-toxic nature, convenient synthesis in a variety of sizes, and ability to attach payloads through various means like electrostatic, covalent or non-covalent interactions.

Thanks to Dr. B. L. V. Prasad, Scientist, Physical and Materials Chemistry Division of National Chemical Laboratory (NCL), Pune and his team who have made painstaking efforts in exploring several biochemical substances that could act as nanoparticle stabilizing agents, which also enhance the functional role of the nanoparticle in carrying the drug and delivering the therapeutic molecules to target cells. It was found that Gellan gum, widely used in food and confectionary industry as thickening and gelling agent, could be used as nanoparticle stabilizing agent, for it has unique structural features. Gellan gum comprises four linked monosaccharides or simple sugars, including one molecule of rhamnose (a sugar found in various plants), one molecule of glucuronic acid (an oxidized glucose molecule), and two molecules of glucose. It is, therefore, a high molecular weight polysaccharide gum.

Gellan gum is produced by culture fermentation of a carbohydrate by the microbe Pseudomonas elodea, which is an aerobic, non-pathogenic, gram-negative bacterium. This water soluble gum having thickening, gelling and stabilizing properties is commercially available and is approved for food, cosmetic and pharmaceutical use in many countries. It has also been an ingredient of hair care products, creams and sunscreens among other such products.  According to Dr. Varsha Pokharkar from Poona College of Pharmacy, Bharati Vidyapeeth University, Pune, who has also contributed to this work, the reducing and stabilizing properties of this gum have been crucial for using it in the synthesis of gold nanoparticles.

 Nanoparticles stabilized with gellan gum also display superior stability to pH changes. Such nanoparticles have been used to load one of the anthracycline rings with antibiotic, Doxorubicin hydrochloride, and tested for their cytotoxic effects against human glioma (brain tumor) cell lines, namely, LN-18 and LN-229.

Dr. Anjali Shiras from National Centre for Cell Science (NCCS), where the activity of nanoparticles on these cells was assessed, says that the drug loaded on nanoparticles show enhanced cytotoxic effect as compared to pure drug taken at same concentrations as present on the nanoparticle surface, while being effective for a longer period of time.

Normally, anti-cancer drugs targeted at brain tumors face the challenge of crossing the Blood Brain Barrier (BBB) that blocks the drug delivery to the tumor site. On the other hand, nanoparticles have been shown to cross this barrier, which is why such drug delivery systems are a better alternative to delivering drugs in tissues of the brain. In this context, gum loaded nanoparticles having many sugar moieties could have an additional advantage as the BBB contains glucose receptors.

           

            Another exciting application of gold nanoparticles is to counter the challenge of multi-drug resistant microorganisms which develop immunity against certain drugs due to their prolonged and excessive use. According to Dr Pankaj Poddar of NCL, Pune, dressing up or capping nanoparticles with antibiotics has worked well. Dr Poddar and his colleagues used cephalexin, a broad-spectrum betalactam antibiotic, for the in situ reduction and capping of gold nanoparticles. Gold nanoparticles have been successful on certain drugs, and research efforts are on for loading some more medicines onto gold nanoparticles for their effective delivery to target body cells. The glittering gold, treasured by us all for its beauty and monetary value, thus has an exciting facet of its usage in delivering medicines effectively.

            The controlled synthesis of nanoparticles is surely an extremely important area of nanotechnology.  In fact, exquisite inorganic nano-scale structures are naturally produced by microorganisms like magnetite particles in magnetotactic bacteria and amorphous silica exoskeletons of diatoms. In an NCL collaboration involving Dr Murali Sastry (Materials Chemistry Division), Dr Rajiv Kumar (Catalysis Division), Dr Absar Ahmad and Dr Islam Khan (Biochemical Sciences Division) has demonstrated the synthesis of silver and gold nanoparticles within the cells of a fungus, Verticillium. The scientists found that treatment of the fungal biomass with aqueous ions of gold chloride resulted in reduction of the metal ions, resulting in intra-cellular formation of gold nanoparticles. As these gold nanoparticles are formed, the fungal biomass dramatically turns purple in colour.

            It is quite exciting that fungi, which are eukaryotic organisms, can be used in nano-synthesis. As fungi are also good sources of enzymes, the enzymatic processes leading to the synthesis of advanced nano-materials have the potential for scale-up. The NCL group has demonstrated that different genera of fungi can be used to synthesize nanoparticles having different chemical compositions.

            In yet another development in nanotechnology, NCL Scientists have shown the biological synthesis of triangular gold nanoprisms. The properties of a metal nanoparticle can be tailored by controlling its size, shape, composition and crystallization. Specific chemicals such as polypeptides secreted by bacteria, namely, Escherichia coli, have been shown to induce the growth of flat, triangular gold nanocrystals at a four per cent yield relative to the total nanoparticle formation. Dr. Murali Sastry of Physical & Materials Chemistry Division, Dr. Absar Ahmed of Biochemical Sciences Division and the team at NCL have demonstrated biological synthesis of large amounts of triangular gold nanoprisms by a single-step, room-temperature reduction of gold salt solution by the extract of the plant, lemongrass (Cymbopogon flexuosus).

            The lemongrass extract on mixing with gold salt solution exhibits a change of colour from pale yellow to a vivid ruby red. The reaction mixture is allowed to stand for six hours to yield a large number of triangular gold nanoparticles of 8 – 18 nm thickness with an edge length of 200-500 nm. This method has reported a yield of 45 per cent. The scientists also enhanced the percentage of gold nanotriangles in the reaction medium up to 95 per cent of the nanoparticle population by repeated centrifugation.

            In fact, Nature has already set the rules for us as it has created innumerable nanostructures each being a masterpiece entity in itself. All we have to do is to understand the secrets of Nature for designing our own nanostructures with unique properties that suit our myriad needs.