Nanopharmacology: A Novel Approach in Therapeutics

 

Vignesh Balaji E, Tamil Selvan A*

Department of Pharmacology PSG College of Pharmacy, Peelamedu, Coimbatore –641004

 

ABSTRACT:

Nanotechnology could be defined as the technology that has allowed for the control, manipulation, study and manufacturing of structure and devices in the ‘nanometer’ size range. These nano-sized objects e.g., “nanoparticles”, take on novel properties and functions that differ markedly from those seen from items made of identical materials. The small size customized surface, improved solubility and multi-functionality of nanoparticles will continue to open many doors and create new biomedical applications. Indeed, the novel properties of nanoparticles offer the ability to interact with complex cellular functions in new ways. This rapidly growing field requires cross- disciplinary research and provides opportunities to design and develop multifunctional devices that can target, diagnose and treat devastating diseases.

 

 

 

INTRODUCTION:

“Nanopharmacology¹” is a relatively newer branch of pharmacology which investigates interaction of a nanomedicine with living systems at the nanoscale level. Modern medicine is increasingly concerned with various surface modified nanocarriers, such as dendrimers, nanoparticles, carbon-based nanomaterials, polymer-drug nanoconjugates, etc., which have immense therapeutic potential by target specific drug delivery, using nano scaffolding and nano containers, owing to the specific physical, chemical and biological properties of these moieties that is related to their nanoscale size range.

 

Nanopharmacology could have their potential medical and pharmaceutical benefits via applications of nanotechnology in the delivery of therapeutic and diagnostics agents. Nanomaterials may be expected to find application in cardiovascular, as well as, renal arena, in the future.

 

NANOSCIENCE AND NANOMEDICINE^2,3:

The word “nano” refers to very small unit of time/length/volume, meaning one billionth part of that unit. In case of length it would be nanometer (nm), which is equal to 10-9meter. Nanoscience is the branch of science that deals with novel materials having a size range of <100nm in at least one dimension. Various nanomaterials have been developed by scientists using different organic and inorganic properties of these materials at the atomic level such as their thermal, optical, electrical, and mechanical characteristics. The applications of nanotechnology in medicine led to emergence of a new discipline in science known as “nanomedicine”. Nanomedicine is the study of nanomaterials to improve diagnosis, control, prevention and treatment of diseases. The goal is achieved by selective delivery of active ingredient, including pharmaceuticals, diagnostic agents, and therapeutic moieties, to a target site using nanomaterials. Nanotherapeutics, nanodiagnotics, engineered nanodevices, nanostructure and nanomedical devices are the tools of nanomedicine to monitor, control, repair and reconstruct a biological system at molecular or even atomic level. The nanoscience and nanotechnology in the development and discovery of nanomedicine to improve therapeutic efficacy and reduce side effects is “nanopharmacology”. Nanopharmacology is concerned with discovery of new drug entities, drug carriers and selection of pharmaceuticals with a purpose to maximize therapeutic index by increasing therapeutic efficacy via reducing toxicity achieved by selective delivery of an active moiety to a target site in the body with the aid of nanotechnology. The effectiveness of a drug depends on its mechanism of action, delivery vehicle or route, correct concentration, distribution and elimination.

 

RECENT INNOVATIONS AND ADVANCES IN NANOPHARMACOLOGY⁴:

Various biocompatible and nano technological carriers are currently being investigated by scientists for pharmacological and biomedical applications. Surface engineered nanostructure such as dendrimers, nano tubes and nanoparticles are also being investigated with the aim to develop efficacious, biocompatible and nontoxic pharmaceutical formulations. In the following sections we shall discuss the pharmacological applications of various plain, as well as, surface engineered nanocarriers. Various applications of these nanocarriers are summarized below.

 

CARBON NANOTUBES (CNTs)⁵:

CNTs are a recent attraction in pharmacology. These are unique carbon-based materials, which are made of thin graphic sheets consisting of condensed benzene rings rolled up into a seamless tubular hollow cylinder. CNTs are made of sp2 hybridized three-dimensional nanoscale tubes. On the basis of the number of walls, CNTs are classified into four    categories; single walled, double-walled, trible –walled and multi-walled carbon nano tubes (SWCNTs, DWCNTs, TWCNTs, and MWCNTs respectively). Since there discovery CNTs are being continually explored in targeting and controlled delivery of drugs due to their unique physico-chemical properties. Functionalization is a wellknown technique of surface modification of nanomaterials. Functionalized CNTs mimic a nano matrix wherein bio actives get entrapped and hence drug release can be controlled temporarily; release may be triggered via stimuli such as pH, temperature, osmotic pressure or enzymes, etc. Functionalized CNTs have been used in drug targeting and imaging, as well as, in effective delivery of gene and nucleic acid (DNA, siRNA, aptamers, and oligo-nucleotides). Complex of CNTs with nucleic acids are translocated into the nucleus of cell via an endocytosis-dependent internalization pathway. Functionalized CNTs also have the ability to deliver water insoluble drugs like taxol derivatives (Paclitaxel and Docetaxel). Further, CNTs have the capacity to readily cross different bio-barriers and pass through the plasma membrane and enter the cytoplasm. This property of CNTs is also called a “nanoneedle” mechanism, which imparts the unique and interesting potentials to transport cargo molecules. The inimitable physico-chemical properties of CNTs have potentials application in the biomedical field.

 

DENDRIMERS⁶:

The term “dendrimers” is derived from the Greek word “Dendron”, meaning “tree”. Mono-dispersity, multivalency, globular shape, nano metric sizes, functional groups, host-guest interactions and large interior cavities are the unique properties of dendrimers. Dendrimers have shown immense potential in controlled and targeted delivery of therapeutic and diagnostic agents. Dendrimers have also shown their potential as tumor targeting and imaging agents, as well as resourceful moiety in neuron capture, photodynamic, photothermal and gene therapy.

 

Dendrimers have emerged as the most versatile nanocarriers system in controlled and target drug delivery. A dendrimer-nanoparticle hybrid composite film provides the controlled release of acyclovir, which can be easily fine-tuned by altering the dendrimers generation and the size of the nanoparticles. Dendrimers are extensively being used for tumor targeting of various bioactive and imaging agents, such as those used in detection of pH and fluorescence signals. Dendrimers have also been used for photon oxygen sensing and resonance imaging, as well as, contrast reagents and blood substitutes. Further, dendrimers have emerged as promising solubilising agents for poorly soluble drug, as intracellular drug delivery vehicles, and to target specific structures thereby improving potentials therapeutic benefit.

 

NANOPARTICLES⁷:

Nanoparticles-mediated drug delivery systems have shown great potentials in drug delivery due to their ability to elicit desired pharmacological responses. The solid lipid nano particle (SLNs), NLCs and lipid-drug conjugates (LDCs) are the modified versions of nanoparticulate delivery systems, which are based on a solid lipid matrix. These nano particulate delivery systems are being explored for drug targeting and intracellular delivery of bioactivies (genes, nucleic acid, drugs). SLNs are made of solid lipids and are characterized by properties such as physical stability, controlled release, good tolerability, and protection of loaded drug from degradation. NLCs and LDCs have been developed to overcome limitations of conventional SLNs like drug leakage, large particle size, chances of gelation and less drug loading. Polymeric nanoparticles (PNPs) have a diameter range from 10 to 100nm, and are generally synthesized from the polymers (naturals and synthetic). Biodegradable and non-biodegradable nanoparticles are the two different types of PNPs. PNPs are usually coated with non-ionic surfactants in order to reduce immunological and inter-molecular interactions.Safe and effective delivery of hydrophobic drug molecules is a serious obstacle in the pharmaceutical industry, which necessitates use of surfactants and solvents like Tween or cremophor. Addition of these solvents often impairs drug distribution and is associated with severe adverse effects. Tween induces hypersensitivity reaction, while cremophor sequesters paclitaxel in micelles drug.

 

 

 

Fig No 1: Potential advantages of Nanocarriers

 

NANOTOXICOLOGY: CONSTRAINTS OF NANOPHARMACOLOGY⁸:

Application of nanotechnology have increased the exposure of human to airborne nano sized particles via ingestion, cutaneous uptake, ingestion and inhalation of nanomaterials, which warrant critical evaluation of the safety and hazards of nanomaterials. This area generated yet another scientific discipline in nanotechnology, termed nano toxicology, which deals with safety evaluation of nanomaterials. Nano-toxicology and nano-pharmacology evaluation of nanotechnology has lead to some constraints on the proposed clinical application of nanomedicines. Inhalation of nano sized particles may result in wide spread deposition of this material into all the parts of respiratory tract mediated by diffusion. Moreover, the small sized particles may enter into systemic circulation and may reach critically sensitive organs like brain, heart, bone marrow, spleen and lymph nodes via cellular uptake and transcytosis across the epithelial and endothelial cell layers. The large surface area of nanomaterials makes them biologically more effective in comparision to large size particles having the same physical and chemical properties. Although recent development in nanotechnology are offering potential benefits in various fields including drug delivery, the safety of these nanomaterials is a critical aspect in regard to human health and environmental protection. One of the most advanced nanocarriers, CNTs, is showing a promising potential in nanopharmacology, but many studies have reported that MWCNTs may cause inflammation and fibrosis if they reach lungs. Hence, it is essential to consider the potential, as well as, safety of such nanomaterials.

 

NANOPARTICLE DELIVERY SYSTEMS:

Nano capsules are vesicular systems in which a drug is confined to a cavity surrounded by a polymer membrane, whereas nanospheres are matrix systems in which the drug is physically and uniformly dispersed. Nanoparticles are solid, colloidal particles consisting of macromolecular substances that vary in size from 10nm to 1000nm. However, particles>200 are not heavily pursued and nanomedicine often refers to devices<200nm (i.e., the width of micro capillaries). Typically, the drug of interest is dissolved, entrapped, adsorbed, attached and encapsulated into or onto a nano-matrix. Depending on the method of preparation nanoparticles, nanospheres or nano capsules can be constructed to possess different properties and release characteristics for the best delivery or encapsulation of the therapeutic agents.

 

These systems in general can be used to provide targeted (cellular or tissue) delivery of drug, improve bioavailability, sustain release of drugs or solubilise drugs for systemic delivery. This process can be adapted to protect therapeutic agents against enzymatic degradation (i.e., nucleases and proteases). Thus the advantages of using nanoparticles for drug delivery are a result of two main basic properties: small size and use of biodegradable materials. Nanoparticles, because of their small size, can extravasate through the endothelium in inflammatory sites, epithelium (e.g.: intestinal tract and liver), tumors or penetrate micro capillaries. In general, the nanosize of these particles allows for efficient uptake by a variety of cell types and selective drug accumulation at target sites. Many studies have demonstrated that nanoparticles have a number of advantages over micro particle (>1μm) as a drug delivery system. Nanoparticles have another advantage over larger micro particles because they are better suited for intravenous delivery. The smallest capillaries in the body are 5-6μm in diameter. The size of particles being distributed into the bloodstream must be significantly smaller than 5μm, without forming aggregates to ensure that the particles do not cause an embolism. The use of biodegradable materials for nano particle preparation allows for sustained drug release within the target site over a period of days or even weeks. Biodegradable nanoparticles formulated from PLGA and PLA have been developed for sustained drug delivery and are especially effective for drugs with an intracellular target. Rapid escape of hydrophobic PCL- coated nanoparticles from endo-lysosomes to the cytoplasms has been demonstrated. Greater and sustained anti-proliferated activity was observed in vascular smooth muscle that were treated with dexamethasone-loaded nanoparticles and then compared to cells given drug in solution. Hence, nanoparticles can be effective in delivering their contents to intracellular targets.

 

TARGETED DRUG DELIVERY SYSTEM⁹:

Targeted drug delivery, sometimes called smart drug delivery, is a method of delivery medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticles-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage forms. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of the drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult and the reduced ability to adjust the dosages. Targeted drug delivery systems have been developed to optimize regenerative techniques. The system is based on a method that delivers a certain amount of a therapeutic agent for a prolonged period of time to a targeted diseased area within the body. This helps maintain the required plasma and tissue drug levels in the body, thereby preventing any damage to the healthy tissue via the drug.

 

 

Fig no 2: Targeted drug delivery based on the nanoparticles

 

There are different types of drug delivery vehicles, such as polymeric micelles, liposome’s, lipoprotein-based drug carriers, nano-particle drug carriers, dendrimers, etc. An ideal drug delivery vehicle must be nontoxic, biocompatible, non-immunogenic, and biodegradable and must avoid recognition by the host’s defense mechanism. This ability for nanoparticles to concentrate in areas of solely diseased tissue is accomplished through either one or both means of targeting passive or active.

 

PASSIVE TARGETING¹⁰:

In passive targeting, the drug success is directly related to circulation time. This is achieved by cloaking the nanoparticles with some sort of coating. Several substances can achieve this, with one of them being polyethylene glycol (PEG). By adding PEG to the surface of the nanoparticle, it is rendered hydrophilic, thus allowing water molecules to bind to the oxygen molecules on PEG via hydrogen bonding. The result of this bond is a film of hydration around the nanoparticle which makes the substance antiphagocytic. The particle obtains this property due to the hydrophobic interactions that are natural to the reticuloendothelial system (RES), thus the drug-loaded nanoparticles is able to stay in circulation for a longer period of time. To work in conjunction with this mechanism of passive targeting, nanoparticles that are between 10 and 1000 nanometers in size have been found to circulate systemically for longer period of time.

 

ACTIVE TARGETING:

Active targeting of drug-loaded nanoparticles enhances the effects of passive targeting to make the nanoparticles more specific to a target site. There are several ways that active targeting can be accomplished. One way to actively target solely diseased tissue in the body is to know the nature of a receptor on the cell for which the drug will be targeted to. Active targeting can also be achieved by utilizing magneto liposomes, which usually serves as a contrast agent in magnetic resonance imaging. Thus, by grafting these liposomes    with a desired drug to deliver to a region of the body, magnetic positioning could aid with this process. By utilizing both passive and active targeting, a drug-loaded nanoparticle has a heightened advantage over a conventional drug. It is able to circulate throughout the body for an extended period of time until it’s is successfully attracted to its target through the use of cell specific ligands, magnetic positioning or pH responsive materials. Because of these advantages, side effects from conventional drug will be largely reduced as a result of the drug loaded nanoparticles affecting only diseased tissue.

 

LIPOSOMAL DRUG DELIVERY SYSTEM¹¹:

The concept of liposomal drug delivery system has revolutionised the pharmaceutical field. Since then active research in the field of liposomes have been carried out and their applications are now well established in various areas, such as drug, biomolecules and gene delivery. Liposomes are spherical vesicles characterised by a bilayer of lipids with an internal aqueous cavity. Liposome structural components are phospholipids or synthetic amphiphiles incorporated with sterols, such as cholesterol, to influence membrane permeability. Thin-film hydration is the most widely used preparation method for liposomes, in which lipid components with or without a drug are dissolved in an organic solvent. The solvent will be evaporated by rotatory evaporation followed by rehydration of the film in an aqueous solvent. The other methods include reverse-phase evaporation, freeze-drying and ethanol injection. Due to extensive development in liposome technology, a number of liposome-based drug formulations are available for human use and many products are under different clinical trials. Encapsulation of drugs in liposomes enhanced the therapeutic indices of various agents, mainly through alterations in their pharmacokinetics and pharmacodynamics. Drugs with different solubility can be encapsulated in liposomes, hydrophobic drugs have affinity to the phospholipids bilayer and hydrophilic drugs are entrapped in aqueous cavity.

 

 

Fig No 3: Schematic representation showing the advantages of formulating drugs in Liposomes

 

Liposomes were first produced in England in 1961 by Alec D. Bangham. One end of each molecule is water soluble, while the opposite end is water insoluble. Water-soluble medications added to the water were trapped inside the aggregation of the hydrophobic ends; fat-soluble medications were incorporated into the phospholipid layer. In some cases liposomes attach to cellular membranes and appear to fuse with them, releasing their or drugs into the cell. In the case of phagocytic cells, the liposomes are taken up, the phospholipid walls are acted upon by organelles called lysosomes, and the medication is released. Liposomal delivery system are still largely experimental; the precise mechanism of their action in the body are under study, as are way in which to target them to specific diseased tissues. A liposome has an aqueous solution core surrounded by hydrophobic members, in the form of a lipid bilayer; hydrophilic solutes dissolved in the core cannot readily pass through the bilayer. Hydrophobic chemicals associate with the bilayer. A liposome can be hence loaded with hydrophobic and hydrophilic molecules. To deliver the molecules to a site of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents; this is a complex and non-spontaneous event.

Fig No 4: Schematic diagram of Liposome

 

Liposomes are used as models for artificial cells. Liposomes can also be designed to deliver drug in other way. Liposomes that contain low (or high) pH can be constructed such that dissolved aqueous drugs will be charged in solution. As the pH naturally neutralizes within the liposome (protons can pass through some membrane), the drug will also be n neutralised. These liposome works to deliver drug by diffusion rather than by direct cell fusion. Drug delivery systems can in principle provide enhanced efficacy and reduced toxicity for anticancer agents. Long circulating macromolecular carriers such as liposomes can exploit the enhanced permeability and retension effect for preferential extravasation from tumor vessels. Liposomal anthracyclines have achieved highly efficient drug encapsulation, resulting in significant anticancer activity with reduced cardio toxicity; include versions with greatly prolonged circulation such as liposomal daunorubicin and pegylated liposomal doxorubicin. Additional liposome constructs are being developed for the delivery of other drugs. The next generation of delivery systems will include true molecular targeting; immune liposomes and other ligand-directed constructs represent an integration of biological components capable of tumor recognition with delivery technologies. Currently approved liposomal drug delivery systems provide stable formulation; provide improved pharmacokinetics and a degree of ‘passive’ or ‘physiological’ targeting to tumor cells. The design modifications that plasma proteins and cell membrane and which contrast them with reactive carriers such as cationic liposomes also prevent interactions with tumor cells. Instead, after extravasation into tumor tissue, liposomes remain within tumor stroma as a drug-loaded depot. Liposomes eventually become subject to enzymatic degradation and phagocytic attack, leading to release of drug for subsequent diffusion to tumor cells.

 

APPLICATION OF NANOPHARMACOLOGY^12,13:

The different fields that find potential applications of nanopharmacology are as follows; Health and medicine, Electronics, Transportation, Energy and environment and Space exploration.

 

Nanotechnology in health and medicine:

Even today various disease like diabetes, cancer, Parkinson’s disease, Alzheimer’s disease, cardiovascular disease and multiple sclerosis as well as different kinds of serious inflammatory or infectious disease (e.g. HIV) constitute a higher number of serious and complex illness which are posing a major problem for the mankind. With the help of nanomedicine early detection and prevention, improved diagnosis, proper treatment and follow-up of disease is possible. Certain nanoscale particles are used as tags and labels, biological can be performed quickly, the testing has become more efficient with the invention of nano devices like gold nanoparticles, and these gold particles when tagged with short segments of DNA can be used for detection of genetic sequence in a simple. With the help of nanotechnology, damaged tissue can be reproduced or repaired. These so called artificially stimulated cells are used in tissue engineering, which might revolutionize the transplantation of organs or artificial implants. Two forms of nano medicine that have already been tested in mice and are awaiting human trials; use of gold nano shells to help diagnose and cure cancer, and the use of liposome as vaccine adjuvant and as vehicles for drug transport. Similarly, drug detoxification is also another application for nanomedicine which has been used successfully in rats. Medical technology can make use of smaller devices are less invasive and can possibly be implanted inside the body and their biochemical reaction times are much shorter. As compared to typical drug delivery nano devices are faster and more sensitive.

 

Nanotechnology in the treatment of neurodegenerative disorders:

One of the most important applications of nanotechnology is in the treatment of neuro degenerative disorders. For the delivery of CNS therapeutics, various nano carriers such as dendrimers, nano gels, nano emulsion, liposomes, polymeric nano particles, solid lipid nano particles and nano suspension have been studied. Transportation of these nano medicines has been effected across various in vitro and in vivo BBB models by endocytosis and transcytosis and early preclinical success for the management of CNS conditions such as, Alzheimer’s disease, brain tumors, HIV encephalopathy and acute ischemic stroke has become possible. The nanomedicine can be advanced further by improving their BBB permeability and reducing their neurotoxicity.

 

Parkinson’s disease:

This can improve current therapy of Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease and affects one in every 100 persons above the age of 65 years, PD is a disease of the central nervous system; neuro inflammatory responses are involved and leads to severe difficulties with body motions. The present day therapies aim to improve the functional capacity of the patient for as long as possible but cannot modify the progression of the neurodegenerative process. Aim of applied nanotechnology is regeneration and neuro protection of the central nervous system (CNS) and will significantly benefit from basic nanotechnology research conducted in parallel with advances in neurophysiology, neuropathology and cell biology. The efforts are taken to develop novel technologies that directly or indirectly help in providing neuro protection and permissive environment and active signaling for guided axon growth. In order to minimize the peripheral side effects of conventional forms of Parkinson’s disease therapy, research is focused on the design, biometric stimulation and optimization of an intracranial nano-enabled scaffold device (NESD) for the site-specific delivery of dopamine to the brain, as a strategy. Peptides and peptide nano particles are newer particles are newer tools for various CNS diseases.

 

Alzheimer’s disease:

Worldwide, more than 35 million people are affected by Alzheimer’s disease (AD), which is the most common form dementia. Nano technology finds significant applications in neurology. These approaches are based on the, early AD diagnosis and treatment is made possible by designing and engineering of a plethora of nanoparticulate entities with high specificity for brain capillary endothelial cells. Nanoparticles (NPs) have high affinity for the circulating amyloid-β (Aβ) forms and therefore may induce “sink effect” and improve the AD condition. In vitro diagnostics for AD has advanced due to ultrasensitive NP-based bio-barcodes and immune sensors, as well as scanning tunneling microscopy procedures capable of detecting Aβ1−40 and Aβ1−42. The recent research on use of nanoparticles in the treatment of Alzheimer’s disease is shown in the figure:

 

 

Fig No 5: Nanoparticles Drug Delivery in Alzheimer’s Disease

 

Nano particle drug delivery & treatment in cancer therapy:

One of the fourth deaths in the United States is from cancer. About 1.2 million Americans are diagnosed with cancer annually & more than 5,00,000 die. Oncomarkers is the signature of a cancer cells and modern nanoparticles developed to conjugate to various molecular markers. A tumor marker is a substance found in the body tissue that can be elevated only in cancer cells. Doxorubicin (DOX) is the most efficient anti-cancer drugs, but DOX can cause death of healthy cells too. That’s why nanoscale capsule can deliver DOX only inside cancer cells using oncomarkers signature. It consists of a DNA- Origami shell covered by immune factors with molecules binding sites on its surface. Nanoparticles delivery starts from blood stream. DOX nanoparticles penetrate inside the cancer cell due to cancer markers on its surface. When nano capsules conjugated with several markers its DNA-Origami shells open releasing DOX inside the cell. DOX successfully delivered. Cancer cell die due to DOX directly will deliver. ‘Minicells’ nanoparticles are used in early phase clinical trial for drug delivery for treatment of patients with advanced and untreatable cancer. The minicells are built from the membranes of mutant bacteria and were loaded with paclitaxel and coated with cetuximab, antibodies and used for treatment of a variety of cancers. The tumor cells engulf the minicells. Once inside tumor, anti-cancer drug destroys the tumor cells. The larger size of minicells plays a better profile in side-effects. The minicells drug delivery system uses lower dose of drug and has less side-effects can be used to treat a number of different cancers with different anti-cancer drugs.

 

Applications in ophthalmology:

The aim of nanomedicine is to monitor, control, construct, repair, and defense and improve human biological systems at the molecular level, with the help of nano devices and nano structures that operate massively in parallel at the unit cell level, in order to achieve medical benefit. Some application of nanotechnology to ophthalmology are include treatment of oxidative stress; measurement of intraocular pressure; theragnostic; use of nano particles for treatment of choroidal new vessels, to prevent scars after glaucoma surgery, and for treatment of retinal degenerative disease using gene therapy; prosthetics and regenerative nano medicine. Treatments for ophthalmic diseases are expected from this emerging field. A novel nanoscale dispersed eye ointment (NDEO) for the treatment of severe evaporative dry eye has been successfully developed. The excipients used as semisolid lipids were coupled with medium-chain triglycerides (MCT) as a liquid lipid; both phases were then dispersed in polyvinyl pyrrolidone solution to form nanodispersion. A transmission electron micrograph showed that the ointment matrix was entrapped in the nano emulsion of MCT, with a mean particle size of about 100nm. The optimized formulation of NDEO was stable when stored for six months and demonstrated no cytotoxicity to human corneal epithelial cells when compared with commercial polymer-based artificial tears. The therapeutic effects of NDEO were evaluated and demonstrated therapeutic improvement, displaying a trend of positive correlation with higher concentration of ointment matrix in the NDEO formulation compared to a marked product. Histological evaluation demonstrated that the NDEO restored the normal corneal and conjunctival morphology and is safe for ophthalmic application. recent research shows applications of various nanoparticulate systems like micro emulsions, nanosuspension, nanoparticles, liposomes, niosomes, dendrimers and cyclodextrins in the field of ocular drug delivery and also depicts how the various upcoming of nanotechnology like nano diagnostics, nano imaging and nanomedicine can be utilized to explore the frontiers of ocular drug delivery and therapy.

 

Applications in operative dentistry:

Nanotechnology aims at the creation and utilization of materials and devices at the atomic and molecular level, supra molecular structures and in the exploitation of unique properties of particles of size 0.1nm to 100nm. Nano filled composite resin materials are believed to offer excellent wear resistance, strength and ultimate aesthetics due to their exceptional polishability and luster retention. In operative dentistry, nano fillers constitute spherical silicon dioxide (SiO2) particles with an average size of 5-40nm. The real innovation about nano fillers is the possibility of improving the load of inorganic phase. The effect of this high filler load is widely recorded in terms of mechanical properties. Micro hybrid composites with additional load of nano fillers are the best choice in operative dentistry.

 

CONCLUSION:

The quest for promising new treatment strategies augmented pharmacological exploration of nanotechnology which led to nanomedicinal advances. The success of nanopharmacology depends on designing of formulations, which can overcome physiological barriers for controlled delivery of bioactivies to yield therapeutic outcomes. Evidences are available supporting the exceptional potential of nanopharmacology in medical sciences. Screening of the nanomaterial’s interactions with physiological components has enabled monitoring and management of living systems. Although at present we have only a superfacial view of nanopharmacology yet a further systematic evaluation of nanomaterials will present a clear picture of the interactions of nanomedicines with living systems. This exploration will provide a platform for close monitoring and controlled manipulation of human biology for the treatment of disease.

 

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Accepted on 01.11.2018            © A&V Publications All right reserved