NOVEL target tissue is adjusted..The areas of

                   NOVEL DRUG DELIVERY SYSTEMINTRODUCTION:                                                                The approaches, the technologies and the systems for the transporting a pharmaceutical compound to the targeted site within the body safely to achieved its desired therapeutic effects  The aim of drug delivery is to help patients by manufacturing clinically useful products.Firstly the convenient drug delivery was developed like oral and transdermal drug delivery systems that transport the drug within their limiting time range like 24 hrs,12 hrs, successfullydeliver the drug efficacy and minimizing the side effects, so with the passage of time the technologies grew and developed such type of system which has to aim the drug approach to its target site rather than by passing through oral, IV route, as with that route certain side effects are associated and the systems has negligible amount of side effects with the specific type of nanoparticles that penetrating to the targeted site of the body.The nanoparticles are used to represent a spectrum of systems including nanocarriers, nanovehicles, nanosystem and nanostructure etc.The purpose of Novel Drug Delivery System is to provide a therapeutic amount of drug to the correct  site in the body to accomplish promptly and then maintain the desired drug concentration. The drug- delivery system should deliver drug at a rate control by the necessarily of the body over a specified term of treatment. Different aspects of drug delivery system Spatial Drug Delivery:Targeting a drug to a specific organ or tissueTemporal Drug Delivery:The drug delivery rate to the target tissue is adjusted..The areas of research and development for NDDS are:• Liposomes• Niosomes• Nanoparticles• Transdermal drug delivery• Implants• Oral system• Micro encapsulation / Microcapsules• Polymer in drug deliveryNovel drug delivery system can be divided into classes. 1. Sustained release drug delivery system.2. Controlled release drug delivery system.Sustained release drug delivery systemIt is a pharmaceutical dosage from formulated to retard the release of a therapeuticeffect such that its look in the systemic circulation is delayed and/ or prolonged andthe plasma profile is sustained in duration . The onset of its pharmaceutical action is often slow,and the duration of its therapeutic effect is sustained. (eg: coated granules)Controlled release drug delivery systemThis system has a meaning that goes beyond the scope of sustained drug action. Itmanifests a predictability and reproducibility in the drug release kinetics. The release of drugsubstances from a controlled release drug delivery system gains at a rate profile that is notonly predictable kinetically but also reproduced from one unit to another.They are classified as follows:I. Rate- preprogrammed drug delivery systemII. Activation – Modulated drug delivery systemIII. Feed – Back Regulated drug delivery systemIV. Site – Targeting drug delivery systemMerits of drug delivery system: 1. Better treatment of many chronic diseases. E.g. Cancer, Asthma, Arthritis.2. Enhanced Bio- availability.3. Reduction in the occurrence and badness of untoward systemic side effects related to high blood plasma drug concentration.4. Sustenance of the total amount of drug administered over the period dose periods.5. Decrease in the total amount drug administered over the period of drug treatment which reduce occurance of systemic and local side effects.6. Prevention from first pass metabolism and gastrointestinal tract degradation.7. Better patient compliance effect from the reduction in the number and frequencyof doses needed to maintain the desired  therapeutic responses.8. Targeting the drug molecule towards the specific affected  tissue or organ make smaller thetoxicity to the normal tissues.9. Versatile and pH dependent system release the drug whenever the body demand.NDDS ACCORDING TO ANTICANCER TREATMENT:                                                                                                                             Novel drug delivey  play a key role in the cancer therapy for treatment.In vivo study of targeted anticancer drug delivery based on cultured human cancer cell expresses a unique surface marker specifically selected to test the target delivery. Also cytotoxicity is commonly examined by the addition of drug delivery system directly to cell grows as a monolayer or in suspension.That studies produces a dose-response curve with an IC50of an anticancer agents, and in vivo the most targeted drug delivery technologies performed on human cancer cell in the immunodeficiency mice. So that system claims the decrease in the tumour size due to certain alteration of genes in the mice and if the treatment stopped so the size rapidly increasing of the cancer site.TARGETED DRUG DELIVERY:                                                       Targeted drug delivery system refers to the approach of drug to the target site within the body in the molecular level and independent of method and route of administration of drug.” OR”Also refers to the molecular level interaction of drug and its receptors.Mostly the targeted drug delivery system depends on the route selection and specifically for the anticancer drugs through the IV administration of the drugs.Formerly work done between late 1960s and the mid 1980s stressed the need for drugs carrier system specifically to change the pharmacokinetics of the before proven drugs whose efficacy might be enhanced by changing the rates of metabolism in liver or clearance by the kidneys. These approaches commonly were not focused to achieved site specific or targeted delivery such as getting a cytotoxic drug to cancerous tissue while remaining other normal, though equally sensitive tissue with the progress in the carrier technology the problem of delivering either single or the entire carrier to the specific site has been addressed during the last few years.There are various drug targeting techniques:1. Nano particles2. Niosomes3. Resealed Erythrocytes4. Microspheres5. Monoclonal antibodies6. Liposomes7. Magnetic microparticlesTYPES OF TARGETING SYSTEM:Passive targetingActive targetingPASSIVE TARGETING:                                        Passive targeting consists of drug accumulation in the area around the tumors with leaky vasculature EPR effect.The EPR effect may be in the effect for IV administered nanoparticles and  >95% of nanoparticles are accumulated in other organs such as liver, spleen etc.So the passive targeting replaced with blood circulation and extravasation, not limited to the drug delivery to the tumors. So successfully the extravasation is achieved by technologies to localized the drug delivery and release at the selective sites within the body such as tumor but not the liver or spleen.ACTIVE TARGETING:                                        Active targeting means to explain the interaction between the drug/drug carrier and the target (tumor) cells especially the ligand- receptor  interaction.”OR”Active targeting is for intracellular localization which occurs only after blood circulation and extravasation due to modifying the surface of nanoparticles with poly (ethylene glycol) or enhancing the EPR effect for drug approach to the target site. CLASSIFICATION OF TARGETED DRUG DELIVERY:                                                                                                Targeted drug delivery can be divided into 2 areas.Systemic targetingIntracellular targetingSYSTEMIC TARGETING:                                              The name indicates systemic means the circulation within blood system and extravasation. In this way the drug deliver to the site through the blood circulation within that target area.INTRACELLULAR TARGETING:                                                           The drug reached to target cells with the drug carriers to help in the approach to the target site by penetrating in to the body proteins.EPR EFFECT:                       The principal of tumor targeting based on EPR effect of nanoparticles first proposed  by Professor Hiroshi Maeda.In EPR effect the blood vessels are more penetrateable for the nanoparticles vasculature to the targeted site of the body.NANO PARTICALES PROPERTIES:                                                              The nano particles in the molecular weight range of 15,000-70,000 g/mol with additional properties that effectively accumulate in a solid tumors.Polymeric micelle systems tested released the encapsulation agent in a matter of only 15 min after IV infusion due to interactions with the blood components.PEGylation:                    Surface modification of nanoparticles with PEGs of various chain length, shape, density, molecular weight and incorporation of different targeting moieties (ligands, antibodies) etc is emerging more promising and technologically advanced drug delivery system in the cancer therapy.Currently more than 35 US FDA approved PEGylated NPs with target number in preclinical studies for both imaging and therapy.Topoisomerase 1 inhibitor,  camptothecin-based drugs (irinotecan, topotecan,SN38, exetecan) etc is reported to be useful in the treatment of many solid tumors.PEGylation is one of the best methods for passive targeting of anticancer therapeutics.FACTOR FOR EFFECTIVE CANCER TREATMENT:                                                                                         Several factors including for effective cancer treatment are;EXTRAVASATION AND INTRATUMORAL DISTRIBUTION:                                                                                                          Drug and its carrier either in different forms fulfill the need at target site through the vasculation where the membrane are more permeable than the normal cell membrane and the distribution are easily held from blood compartment to the tumor tissue that is governed by two methods: Convection: The driving force behind the convective flow is the pressure gradient. Solid tumors develop higher interstitial fluid pressure, ranging from 5 to 40mmHg depending on tumor size.Diffusion: Drug and carrier move towards the tumor cell through the membrane permeation by the random Brownian motion diffuse to the targeted tissue depend upon the size, shape, surface, properties and concentration within the blood vessels.OVEREXPRESSION:                                   “Overexpression” of a specific maker on the cell surface is one of the most widely used words in the literature to justify cell-specific targeted drug delivery. This term is only a relative description between target cells and non-target cells based on the differences in expression levels per unit cell mass (or tissue area).In a hypothetical case, if any particular receptor is 100 fold overexpressed on target cells, it can be 10% (target cell) vs. 0.1% (non-target cell). If the mass of non target cells is more than 500-fold that of target cell mass, the amount of nanoparticles interacting with non-target cells would be 5 times more than that with target cells.

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