SEMINAR REPORT
ON
“NANO DRUG DELIVERY SYSTEM”
Presented towards partial fulfillment for the
Award of B.Pharmacy.
Seminar presented by : Bharath Reddy.K
Regd.No : 07FN1R0004
Class : IV B.Pharm,I Semester
Under the Guidance of
Smt. Shireesha.T M.Pharm.,(Ph.D)
Department of Biotechnology
FATHIMA INSTITUTE OF PHARMACY
(Approved by AICTE, New Delhi and affiliated to JNTU,Anantapur.)
KADAPA
FATHIMA INSTITUTE OF PHARMACY
(Approved by AICTE, New Delhi and Affiliated to JNTU)
KADAPA
certificate
This is to certify that the seminar entitled “Nano Drug Delivery System” is a bonafied work of Mr. K.Bharath Reddy (07FN1R0004) carried out under the guidance of Smt. Shireesha.T M.Pharm.,(Ph.D) Department of Biotechnology in partial fulfillment for the award of Degree in Bachelor of Pharmacy.
Lecturer in Charge Principal
Acknowledgement
The foremost credit for the presentation goes to our guide Smt. Shireesha.T M.Pharm,(Ph.D) Department of Biotechnology , for her collaborative effort to develop the seminar. Her candor, painstaking, meticulous efforts along with her creative mind paid attention to design the seminar successfully. Her patience, gracious manner friendship encouraged me to seek new professional challenges and extend my boundaries towards educational endeavor.
I wish to acknowledge our beloved principal Mr.U.Mohan Kumar, M.Pharm., (Ph.D)., Department of Pharmaceutics, for his promptitude in all matters carefully through his continuous encouragement and help. I thank them profoundly.
I am thankful to my parents and all of my friends for their support so as to prepare the designed manuscript.
This work wouldn’t have been fulfilled with out God’s grace and true blessings on me.
Bharath Reddy.K,
IV-1 B.Pharmacy,
07FN1R0004
“NANO DRUG DELIVERY SYSTEM”
Contents:
· Abstract
· Introduction
· Challenges
· Drug delivery carriers
· Achievements
· Conclusion
ABSTRACT : 1
Nanotechnology received a lot of attention with the never-seen-before enthusiasm because of its future potential that can literally revolutionize each field in which it is being exploited. In drug delivery, nanotechnology is just beginning to make an impact, because materials reduced to nanoscale can show different properties compared to what they exhibit on a macroscale. Drug delivery nanosystems constitute a significant portion of nanomedicine. Many of the current “nano” drug delivery systems, however, are remnants of conventional drug delivery systems that happen to be in the nanometer range, such as liposomes, polymeric micelles, nanoparticles, dendrimers, and nanocrystals. Liposomes and polymer micelles were first prepared in 1960’s, and nanoparticles and dendrimers in 1970’s. The importance of nanotechnology in drug delivery is in the concept and ability to manipulate molecules and supramolecular structures for producing devices with programmed functions. Conventional liposomes, polymeric micelles, and nanoparticles are now called “nanovehicles”. Due to nano particles, modern chemistry has reached the point where it is possible to prepare small molecules to almost any structure, which are very useful in manufacturing variety of useful pharmaceuticals.
So nanotechnology may be able to create many new materials with a vast range of applications, in medicine and energy production. The main motto of nano drug delivery system is “target delivery system and controlled drug delivery system”, which reduces the unwanted side effects, and unwanted actions. Nano drug delivery system results in effective targeting and patient compliance.
Introduction: 2
This Seminar report discusses potential use of nanotechnology in drug delivery systems and pharmacotherapeutics.
Several areas of medical care are already benefiting from the advantages of nanotechnology. One of them is drug delivery, which is one of the key priorities in nanomedicine research along with diagnostics and regenerative medicine.
Drug delivery is being approached by nanomedicine by developing nanoscale particles or molecules to improve the bioavailability of a drug. Bioavailability of a drug is the presence of drug particles/molecules there where they are needed in the body and where they will do their best. The main focus of drug delivery is increasing the bioavailability to the maximum both at certain places in the body and over a period of time. This can be achieved by nanotechnology-based devices. Estimated 65 billion dollars per year are being wasted because of the poor bioavailability.
Drug delivery systems (nanoparticles) can be designed to improve the threapeutic and pharmaceutical properties of a drug. Nanoparticles have those unusual properties that significantly improve the drug delivery. Nanoparticles are small in size, so the cells accept them unlike other elements which are much bigger and they’re being rejected.
Drug delivery mechanisms are constantly being developed, including the ability to transfer drugs through cell membranes into the cytoplasm. This is important because many diseases can only be impeded by drugs that make it through the membrane.
Drug molecules can be used more efficiently by triggered response.
Molecules are placed in the patient’s body and they activate themselves only when encountering a particular signal. To convey sufficient dose of drug to lesion certain carriers are required so nano and mcro particles have got potential applications for administration of
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therapeutic molecules. Nano drug delivery is about getting the right amount of medication to the right location at right time.
Nanoparticles:
A nanoparticle is submicroscopic solid particle with a size ranging from 1-100 nm. We know that one nanometer is equal to 10 angstroms. Materials used in the preparation of nanoparticles are sterilizable, nontoxic, and biodegradable like albumin, ethylcellulose, gelatin polyesters etc.. Nanoparticles have been successfully applied to medical diagnostics by taking advantage to other rapid uptake by reticulo endothelial system and sequestration by liver Kupffer’s cells. The reticulo endothelial system consists of phagocytic cells designed to cleanse the bloodstream of bacteria, viruses, cell debris, and other unwanted foreign particles. Such specific cellular processing of nanoparticles points to the possibility of using nanoparticles to target drugs to the liver and phagocytic cells. To prolong the circulation, nanoparticles should be small enough(≤ 200 nm) or deformable to escape the simple filtration in the spleen. Besides size, the surface of nanoparticles can be modified to avoid opsonization. Opsonization is the adsorption of protein capable of interacting with surface receptors on phagocytic cells. PEGlyation (i.e attaching polyethylene glycol [PEG] to particles) is perhaps the most explored approach to avoiding protein adsorption. PEG can be adsorbed or covalently linked to the surface of particles. The PEG chains exposed on the particle surfaces confer hydrophilicity to the particles and thus effectively suppress the binding ot opsonins through hydrophobic interaction. PEG is also believed to sterically hinder opsonins from interaction. At present, few nanoparticles exist as extended-release systems for delivery of the entrapped drug over a period of days. The permeable vascular endothelia in lymph nodes and bone marrow are capable of removing small-sized particles
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from the circulation. Hence, nanoparticles can promise targeted delivery to inflammation sites such as arthritic joints, to solid tumors, and to hematological malignancies simply because of size exclusion/permeation effect.
Drug delivery technology important to Pharmaceutical industry :
Obviously drug delivery technology is important to Pharmaceutical industry as
Drug delivery formulations involve low cost research compared that for discovery of new molecule.
Minimizing the drug use would significantly reduce the effective cost of drug which would give financial relief to the patients
Novel means of delivery particularly using nano carriers can allow branded drugs to be rescued from abyss of generic competition(may be called resurrection of drug)
Challenges:
1.Reduced side effects
2.Continuous dosing (sustained release)
3.Improved mobility
4.Improved efficacy
5.Reduced environmental impact (elimination of CFC’s)
6.Effective Targeting
7.Patient Compliance
8.Cost effectiveness
9.Product life extension
10.Prevention of drug from biological degradation.
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Why should we use nano drug delivery system ?
Drugs with narrow therapeutic indexes create a major challenge for pharmaceutical scientists ,during their developments. Application of nanotechnology for the delivery of such drugs can significantly overcome this problem.
We are using nano drug delivery system for target drug delivey, why means target drug delivery implies selective and effective localization of drug into the targets at therapeutic concentrations with limited access to nontarget sites. A nano drug delivery system is preferred in the following situations.
1.Pharmaceutical: drug instability, low solubility.
2.Pharmacokinetic(what body does to the drug): short half-life, large volume of distribution, poor absorption.
3.pharmacodynamic(what drug does to the body):low specificity, low therapeutic index.
Targeted drug delivery may provide maximum therapeutic activity by preventing drug degradation or inactivation during transit it target sites. Meanwhile , it can protect the body from adverse effects because of inappropriate disposition, and minimize toxicity of potent of drugs by reducing dose. An ideal targeted delivery system should be nontoxic, biocompatible, biodegradable, and physicochemicaly stable in vivo and in vitro. The preparation of the delivery system must be reasonably simple, reproducible, and cost –effective.
Drug delivery carriers:
Drug delivery carriers are useful for carrying the drug from site of administration to site of action. Some of the drug delivery carriers include:
Liposomes
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Micelles
Niosomes
Dendrimers
Liposomes:
Liposomes are artificially prepared vesicles made of lipid bilayer. Liposomes can be filled with drugs, and used to deliver drugs for cancer and other diseases. Liposomes can be prepared by disrupting biological membranes, for example by sonication.
Liposomes can be composed of naturally-derived phospholipids with mixed lipid chains (likeegg phosphatidylethanolamine) or other surfactants. Liposomes should not be confused withmicelles and reverse micelles composed of monolayers
Liposomes are used for drug delivery due to their unique properties. A liposome encapsulates a region on aqueous solution inside ahydrophobic membrane; dissolved hydrophilic solutes cannot readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to sites of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents. By making liposomes in a solution of DNA or drugs (which would normally be
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unable to diffuse through the membrane) they can be (indiscriminately) delivered past the lipid bilayer. There are three types of liposomes - MLV (multilamillar vesicles) SUV (Small Unilamellar Vesicles) and LUV(Large Unilamellar Vesicles). These are used to deliver different types of drugs. Drug loading capacity varies among different types of liposomes.
Liposomes are used as models for artificial cells. These liposomes work to deliver drug by diffusion rather than by direct cell fusion. Another strategy for liposome drug delivery is to target endocytosis events. Liposomes can be made in a particular size range that makes them viable targets for natural macrophage phagocytosis. These liposomes may be digested while in the macrophage's phagosome, thus releasing its drug. Liposomes can also be decorated with opsonins and ligands to activate endocytosis in other cell types.
The use of liposomes for transformation or transfection of DNA into a host cell is known as lipofection.
In addition to gene and drug delivery applications.
Micelle:
Block copolymer micelles are among the newest nanoparticles currently under investigation. Copolymers are polymers composed of several different monomeric units. Block copolymers are defined as polymers composed of terminally connected structures. . The features of each monomeric segment can be modified without affecting the others because of separation from other monomeric units. Block copolymers are subdivided into three types,
- AB
- ABA
- (AB)n multisegments.
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AB-type copolymers are the most appropriate candidates for the formation of polymeric micelle drug carriers in terms of size, aggregation number, and micelle stability. Usually, the AB – type block copolymers are composed of both hydrophilic poly(ethylene oxide) PEO and hydrophobic blocks such as poly(polypropylene oxide) PPO , which allows the polymers to self assemble as micelle in an aqueous media with hydrophobic cores and highly hydrated outer shells. Therefore , a key function of copolymer micelles is to solubilize hydrophobic drugs, such as taxol (anti cancer drug). Hydrophobic drugs can be incorporated into the hydrophobic core by covalent or noncovalent interaction. The polymeric micelle has diameter of about 20 to 40 nm based on atomic force microscopy, dynamic light scattering measurement, and transmission electron microscopy. 
The size is very important for the micelle to escape clearance because it is believed that the RES recognition and elimination is lower for particles under 100 nm. Hence, polymeric micelles could be long circulation in the blood because of htier small size as well as hydrophilic shell. Prolonged circulation allows polymeric micelles to accumulate at solid tumors as a result of the so called enhanced permeability and retention (EPR) effect. Micelles based on PEO-block-PLA(poly lactic acid) or PEO –block-PLGA(poly lactic-co-glycolic acid) can gradually release drugs. Release of the drug from PEO –PLA micelles may be controlled by degradation of PLA. The stability
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of micelle, micelle core hydrophobicity, and the spacer groups used in binding the drugs to polymer backbones all can play roles in controlling drug release. In other words, a drug independent delivery system can be designed with its release rate or pattern dictated by the carrier. Other promising biological properties have been discovered with block copolymer micelles, including inhibition of P- glycoprotein responsible for multidrug resistance in cancer cells by PEO – block- PPO – block- PEO micelles, enhancement of drug transport across the blood brain barrier by the same block micelles, and reduction of self- aggregation and toxicity of amphotericin B by PEO–block-poly(beta-benzyl-1-aspartate) micelles.
Difference between Liposomes, Micelles, Niosomes:
Liposomes and Micelles:
Liposomes are used to carry both lipophillic drug and and lipophobic drug but Micelle is only used for the delivery of lipophillic which is solubilized by micellar solution in a water environment.
Liposomes and Niosomes:
Liposomes and Niosomes are functionally same but structurally different, as liposomes are prepared from neutral double chain phospholipids which can undergo degradation sometimes but Niosomes are prepared from uncharged single chain surfactants.
Dendrimers:
Dendrimers are repeatedly branched, roughly spherical large molecules. The name comes from the Greek word "δένδρον" (pronounced dendron), which translates to "tree". Synonymous terms for dendrimer include arborols and cascade molecules. However, dendrimer is currently the internationally accepted term. A dendrimer is typically symmetric around the core, and often adopts a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point. A dendrimer is generally described as a macromolecule, which is characterized by its highly branched 3D structure that provides a high degree of surface functionality and versatility. Dendrimers have often been refered to as the “Polymers of the 21st century”. Dendrimer chemistry was first introduced in 1978 by Fritz Vogtle and coworkers (1). He synthesized the first “cascade molecules”.. It is also called arborols from the Latin word ‘arbor’ also meaning a tree. Drug delivery
Approaches for delivering unaltered natural products using polymeric carriers is of widespread interest, dendrimers have been explored for the encapsulation of hydrophobic compounds and for the delivery of anticancer drugs. The physical characteristics of dendrimers, including their monodispersity, water solubility, encapsulation ability, and large number of functionalizable peripheral groups, make these macromolecules appropriate candidates for evaluation as drug delivery vehicles. 
There are three methods for using dendrimers in drug delivery: first, the drug is covalently attached to the periphery of the dendrimer to form dendrimer prodrugs, second the drug is coordinated to the outer functional groups via ionic interactions, or third the dendrimer acts as a unimolecular micelle by encapsulating a pharmaceutical through the formation of a dendrimer-drug supramolecular assembly. The use of dendrimers as drug carriers by encapsulating hydrophobic drugs is a potential method for delivering highly active pharmaceutical compounds that may not be in clinical use due to their limited water solubility and resulting suboptimal pharmacokinetics. Dendrimers have been widely explored for controlled delivery of antiretroviral bioactives . The inherent antiretroviral activity of dendrimers enhances their efficacy as carriers for antiretroviral drugs. The encapsulation increases with dendrimer generation and this method may be useful to entrap drugs with a relatively high therapeutic dose. Studies based on this dendritic polymer also open up new avenues of research into the further development of drug-dendrimer complexes specific for a cancer and/or targeted organ system. These encouraging results provide further impetus to design, synthesize, and evaluate dendritic polymers for use in basic drug delivery studies and eventually in the clinic.
Niosomes:
Niosomes are non-ionic surfactant vesicles obtained on hydration of synthetic nonionic surfactants, with or without incorporation of cholesterol or other lipids. They are vesicular systems similar to liposomes that can be used as carriers of amphiphilic and lipophilic drugs.
Niosomes are promising vehicle for drug delivery and being non-ionic, it is less toxic and improves the therapeutic index of drug by restricting its action to target cells. In niosomes, the vesicles forming amphiphile is a non-ionic surfactant such as Span – 60 which is usually stabilized by addition of cholesterol and small amount of anionic surfactant such as dicetyl phosphate. Since the structure of the niosome offers place to accommodate hydrophilic, lipophilic as well as ampiphilic drug moieties, they can be used for a variety of drugs. Niosomes may be unilamellar or multilamellar depending on the method used to prepare them.
The niosome is made of a surfactant bilayer with its hydrophilic ends exposed on the outside and inside of the vesicle, while the hydrophobic chains face each other within the bilayer. Hence, the vesicle holds hydrophilic drugs within the space enclosed in the vesicle, while hydrophobic drugs are embedded within the bilayer itself. The figure below will give a better idea of what a niosome looks like and where the drug is located within the vesicle. 
.The vesicles can act as a depot to release the drug slowly and offer a controlled release
Niosomes are a novel drug delivery system that are finding application in:
§ drug targeting
§ antineoplastic treatment
§ leishmaniasis treatment
§ delivery of peptide drugs
§ carriers for haemoglobin
§ transdermal drug delivery systems
§ cosmetics
Achievements:
v Development of one dose a day ciprofloxacin using nanotechnology
v Tumor targeted taxol delivery using nanoparticles in Phase 2 clinical trial stage
v Improved ophthalmic delivery formulation using smart hydrogel nanoparticles
v Oral insulin formulation using nanoparticles carriers.
v Liposomal based Amphotericin B formulation by PEO-block-poly(beta-benzyl-1-aspartate) micelles.
Conclusion:
It appears that nano drug delivery systems hold great potential to overcome some of the barriers to efficient targeting of cells and molecules in inflammation and cancer by a drug like paclitaxel(Taxol). There also is an exciting possibility to overcome problems of drug resistance in target cells and to facilitating movement of drugs like levodopa and methyldopa across barriers such as those in the brain. The challenge, however, remains the precise characterization of molecular targets and to ensure that these molecules are expressed only in the targeted organs to prevent effects on healthy tissues. There is a future scope of delivering drugs for tuberculosis. Furthermore, because nanosystems increase efficiency of drug delivery, the doses may need recalibration. Nevertheless, the future remains exciting and wide open.
References:
1. Remingtons The Science and Practice of Pharmacy, volume 1, 21st edition.
2. Comphrehensive pharmacy review by Leon Shargel.
3. Ansel’s Pharmaceutical dosage forms and Drug delivery systems.
5. Controlled drug delivery systems by N.K. Jain
6. www.nanomedicinecenter.com
8. www.biopolymer.group.shef.ac.uk
9. www.boomer.org
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