targeted drug delivery- a review - wjpps

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Nov 2, 2013 - originated from the Paul Ehrlich, who was a microbiologist, proposed the idea of drug delivery in the form of magic bullet. Targeted drug ..... 1 Mrs Jaya Agnihotri, Dr. Shubhini Saraf, Dr. Anubha Khale, Targeting: New Potential.
WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES E.Bhargav et al. World Journal of Pharmacy and Pharmaceutical Sciences Volume 3, Issue 1, 150-169. Review Article ISSN 2278 – 4357

TARGETED DRUG DELIVERY- A REVIEW E.Bhargav*, N.Madhuri, K.Ramesh, Anand manne, V.Ravi JSS College of pharmacy, Bannimantap, Mysore-15 (Karnataka), India. ABSTRACT

Article Received on 12 October2013, Revised on 02 November 2013, Accepted on 10 December 2013

At present 95 percent of all new potential therapeutics have poor pharmacokinetic and biopharmaceutical properties. Hence there is need to develop a suitable drug system that distributes the therapeutically active drug molecule only to site of action, without affecting healthy

*Correspondence for

tissue or organ. Among drug carrier soluble polymers, microparticles

Author:

made of insoluble (or) biodegradable natural and synthetic polymers, microcapsules, cells, cell ghosts, neutrophils, fibroblasts, artificial

* E.Bhargav JSS College of pharmacy,

cells, lipoproteins, lipososmes and micelles, immune micelle,

Bannimantap, Mysore-15

monoclonal antibodies can be taken into consideration. Liposomes are

(Karnataka), India.

micro particulate lipoidal vesicles which are under extent of

[email protected]

therapeutic investigation as drug carriers for improving the delivery of

therapeutic agents. Most clinical applications of liposomal drug delivery are targeting to tissue with or without expression of target recognition molecules on lipid membrane. Microspheric drug delivery system has gained enormous attention due to its wide range of application as it covers targeting the drug to particular site to imaging and helping the diagnostic features. In future by combining various other strategies, microspheres will find the central place in novel drug delivery, particularly in diseased cell sorting, diagnostics, gene & genetic materials. Monoclonal antibody technique involves fusing a normal antibody producing B cell with a myeloma cell to produce a hybrid cell or hybridoma they are excellent candidates as carriers of therapeutic agents for delivery to specific sites. This paper explores various aspects of nanoparticles, microsphere, liposomes and monoclonal antibodies formulation, characterization, effect of their characteristics and their applications in delivery of drug molecules. KEYWORDS:

Targeted drug delivery,

Microspheres,

Nanoparticles,

Liposomes,

Monoclonal antibodies.

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INTRODUCTION The very slow progress in the treatment of severe diseases has led to the adoption of a multidisciplinary approach to the targeted delivery and release of drugs, underpinned by nano science and nano technology. Drug delivery and targeting systems under development aim to minimize drug deprivation and avert harmful side effects and enhance the availability of the drug at the disease site. The concept of designing targeted delivery system has been originated from the Paul Ehrlich, who was a microbiologist, proposed the idea of drug delivery in the form of magic bullet. Targeted drug delivery means accumulation

of

pharmacologically active moiety at desired target in therapeutic concentration at the same restricting its access to normal cellular lining, thus minimizing therapeutic index. The drug can be targeted to intracellular sites, virus cells, bacteria cell and parasites using different scientific strategies have proven highly effective. The minimum distribution of the parent drug to the non target cells with higher and effective concentration at the targeted site certainly maximize the benefits of targeted drug delivery. The design and development of potential carriers for cell-specific delivery of therapeutics should be based on recognition sites on the surface of target cells as well as on insight into the internalization and further cellular disposition of such macromolecules. The choice of carrier system to be used in drug targeting strategies depends on which target cells should be reached and what drug needs to be delivered. Carriers can be divided into soluble, cellular carriers, particle type. Particle type carriers comprise liposomes, lipid particles (low and high density lipoproteins, LDL and HDL respectively), polymeric micelles, nanoparticles, microspheres. Soluble carriers consist of monoclonal antibodies and fragments thereof, modified plasma proteins, peptides, and biodegradable carriers consisting of polymers of various chemical composition. Liposomes are small vesicles composed of unilamellar or multilamellar phospholipids bilayers surrounding one or several aqueous compartments. Charge, lipid composition and size (ranging from 20 to 10000 nm) of liposomes can be varied and these variations strongly affect their behaviour in vivo. Nanoparticles are defined as particulate dispersions or solid particles with a size in the range of 10-1000nm. The drug is dissolved, entrapped, encapsulated or attached to a nano particle matrix. Microspheres can be defined as structure made up of continuous phase of one or more miscible polymers in which drug particles are dispersed at the molecular or macroscopic level. It has a particle size of (11000nm).monoclonal antibodies involves fusing a normal antibody producing B cell with a myeloma cell to produce a hybrid cell or hybridoma.

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In addition to Parenteral application of microspheres and nanoparticles for cell selective delivery of drugs, they have more recently been studied for their application in oral delivery of peptides and peptidomimetics. Drug targeting: A Targeted drug delivery system is preferred in the following situations

PROPERTIES OF TARGETED DRUG DELIVERY 

It should be nontoxic, biodegradable, biocompatible and physicochemical stable invivo and invitro



Confine drug delivery to target cells or tissue or organ or should have uniform capillary distribution.



Predictable and Controllable and rate of drug release.



Drug release should not influence the drug delivery.



Therapeutic amount of drug release.



Minimal drug leakage during transit



Carrier used should be biodegradable or readily eliminated from the body without any problem and no carrier should induce modulation of diseased state.

COMPONENTS OF TARGETED DRUG DELIVERY Target: Target means specific organ or a cell or group of cells, which in chronic or acute condition need treatment. Carrier or marker:

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Carrier is one of the special molecule or system essentially required for effective transportation of loaded drug up to the pre selected sites. They are engineered vectors, which retain drug inside or onto them either via encapsulation and/ or via spacer moiety and transport or deliver it into vicinity of target cell. STRATEGIES OF DRUG TARGETING 

Passive Targeting: Drug delivery systems which are targeted to systemic circulation are characterized as Passive delivery systems. The ability of some colloid to be taken up by the Reticulo Endothelial Systems (RES) especially in liver and spleen made them ideal substrate for passive hepatic targeting of drugs.



Inverse Targeting: In this type of targeting attempts are made to avoid passive uptake of colloidal carrier by RES and hence the process is referred to as inverse targeting. To achieve inverse targeting, RES normal function is suppressed by pre injecting large amount of blank colloidal carriers or macromolecules like dextran sulphate. This approach leads to saturation of RES and suppression of defense mechanism. This type of targeting is a effective approach to target drug(s) to non-RES organs.



Active targeting: In this approach carrier system bearing drug reaches to specific site on the basis of modification made on its surface rather than natural uptake by RES. Surface modification technique include coating of surface with either a bioadhesive, nonionic surfactant or specific cell or tissue antibodies (i.e. monoclonal antibodies) or by albumin protein.



Dual Targeting: In this targeting approach carrier molecule itself have their own therapeutic activity and thus increase the therapeutic effect of drug. For example, a carrier molecule having its own antiviral activity can be loaded with antiviral drug and the net synergistic effect of drug conjugate was observed.



Double Targeting: When temporal and spatial methodologies are combined to target a carrier system, then targeting may be called double targeting. Spatial placement relates to targeting drugs to specific organs tissues, cells or even subs cellular compartment .whereas temporal delivery refers to controlling the rate of drug delivery to target site.

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DEVICES BASED ON NANOTECHNOLOGY

S.no Nanocarriers

Description

1

They are hollow cylinder

Nano tubes

made

of

Image

carbon,

atoms

which can be filled and sealed for potential drug delivery. Help to identify DNA changes associated with cancer cells 2

Nano shells

Nano

shells

are

hollow

silica spheres covered with gold.

Has

potential

for

targeting cancerous drug 3

Quantum dots

These are tiny crystals that glow

when

stimulated

by

these

are

ultraviolet

light. The latex beads filled with these crystals when stimulated by light, emit the color that lights up the sequence of interest. Latex beads filled with crystals can be designed to bind to specific DNA sequences. 4

Dendrimers

Dendrimers are new class of macromolecules which have a symmetric core and form the 3-D spherical structure. These have branching shape which

gives

them

vast

amounts of surface area to

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biologically

active

molecules can be attached. Useful in gene transfection and medical imaging.

CARRIERS FOR TARGETING DRUGS NANOPARTICLES: Rolland et. al., (1989) designed a site specific drug delivery system consisting of poly metacryclic nanoparticles. The main goal in designing nanoparticles as a delivery system are to control size of particle, surface characteristics and discharge of pharmacologically active agents in order to achieve the site-specific action of the drug at the therapeutically optimal rate and dose regimen. Advantages 

Particle size and surface properties of nanoparticles can be easily manipulated to achieve both passive and active drug targeting after parenteral administration.



Nano particles control and prolong release of the drug during the transportation and at the site of localization, altering organ distribution of the drug and subsequent clearance of the drug so as to achieve increase in drug therapeutic efficacy and reduction in side effects.



Controlled release and particle degradation characteristics can be readily modulated by the choice of matrix constituents.



Specific targeting to particular site can be achieved by attaching targeted ligands to surface of particles or use of magnetic guidance. In spite of these advantages, nanoparticles do have limitations. For example, their small size and large surface area can lead to particle-particle aggregation, making physical handling of nanoparticles difficult in liquid and dry forms. In addition, small particles size and large surface area readily result in limited drug loading and burst release. These practical problems have to defeat before nanoparticles can be used clinically or made commercially available.

Preparation Nanoparticles can be prepared from a variety of materials such as polysaccharides, proteins and Synthetic polymers. Selection of matrix materials depends on many factors including: (a) size of nanoparticles required; (b) inherent properties of the drug, e.g., stability; (c) surface

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characteristics such as charge and permeability; (d) degree of biodegradability, biocompatibility and toxicity; (e) Drug release profile desired; and (f) Antigenicity of the final product. Different techniques like polymerization, preformed polymers or ionic gelation etc are used.  Preparation of nanoparticles from dispersion of preformed polymer : Dispersion of drug in preformed polymers is a common technique used to prepare biodegradable nanoparticles from poly (lactic acid) (PLA), poly (D, L-glycolide) (PLG), poly (D, L-lactide-co-glycolide) (PLGA). These can be accomplished by different methods described below. a) Solvent evaporation b) Nano precipitation c) Emulsification/solvent diffusion d) Salting out e) Dialysis f) Supercritical fluid technology (SCF)  preparation of nanoparticles from polymerization of monomers a) Emulsion b) Mini emulsion c) Micro emulsion d) Interfacial polymerization e) Controlled/Living radical polymerization  Ionic gelation or coacervation of hydrophilic polymers ii.

TECHNIQUES

FOR

PHYSICOCHEMICAL

CHARACTERIZATION

OF

NANOPARTICLES Parameter

Technique

Particle size and morphology

Transmission scanning microscopy,

electronic

microscopy,

(electron,force,tunneling) freeze-fracture

electron

microscopy, photon correlation spectroscopy Drug content invitro drug release

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Ultra centrifugation followed by quantitative

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Molecular weight crystallinity

Gel

permeation

chromatography,

X-ray

diffraction, differential scanning calorimetry Surface charge

Zeta potential measurement, hydrophobic

Surface hydrophobicity

interaction chromatography, contact angle measurement

Surface chemical analysis

Secondary ion mass spectrometry, X-ray photoelectron spectroscopy, nuclear magnetic resonance,

fourier

transform

Infrared

spectroscopy Protein adsorption

Two-

dimensional

polyacrylamide

gel

electrophoresis iii.

APPLICATIONS

Application

Material

Cancer therapy

Poly(alkyl

purpose cyanoacrylate) Targeting, reducing toxicity,

nanoparticles cancer

with

agents,

anti enhanced oligo tumour

nucleotides Intracellular targeting

Poly(alkyl

uptake agents,

of

anti

improved

invitro and invivo stability cyanoacrylate) Target

reticuloendothelial

polyester nanoparticles with intercellular infections anti parasitic or anti viral agents Prolonged circulation

systemic Poly esters with adsorbed Prolonged poly

ethylene

glycols

drug

or effect, avoid uptake by the

pluronics Vaccine adjuvant

systemic

reticuloendothelial system

Poly (methyl methacrylate) Enhanced immune response nanoparticles vaccines(oral

with alternate acceptable adjuvant and

IM

immunization) Per oral absorption

Poly (methyl methacrylate) Enhanced

bioavailability

nanoparticles with proteins protection from GIT enzymes

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Ocular delivery

Poly (methyl methacrylate) Improved retention of drug/ nanoparticles with steroids , reduced wash out anti-inflammatory anti-bacterial

agents,

agents

for

glaucoma Oligonuleotide delivery

Alginate nanoparticles , poly Enhanced (D,L

–lactic

delivery

of

acid) oligonucleotides

nanoparticles DNA delivery

DNA- gelatin nanoparticles, Enhanced DNA- chitosin nanoparticles

delivery

significantly

and higher

expression levels Other applications

Poly(alkyl

cyanoacrylate) Crosses blood-brain barrier,

nanoparticles with peptides immunoassays, Poly(alkyl nanoparticles, with

cyanoacrylate) absorption and permeation nanoparticles for transdermal applications,

adsorbed

enzymes, enzyme immunoassays, radio

nanoparticles radioactive

with imaging agents, oral delivery or

contrast, of peptides

copolymerized nanoparticles

,improved

peptide of

activated

peptides

LIPOSOMES: Liposomes were first described by Bangham in 1965, while studying the nature of cell membranes. The name liposome is derived from two Greek words: 'Lipos' meaning fat and 'Soma' meaning body. Mechanisms by which Liposomes act are as follows: 1. Liposome attaches to cellular membrane and appears to fuse with them, releasing their content into the cell. 2. They are taken up by the cell and their phospholipids are incorporated into the cell membrane by which the drug trapped inside is released 3. In case of phagocyte cell, the Liposomes are taken up, the phospholipid walls are acted upon by organelles called lysosomes and the active pharmaceutical ingredients are released.

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Advantages 

Biodegradable, biocompatible, flexible, Non ionic



Can carry both water soluble and lipid soluble drugs



Increased efficacy.



Increased stability via encapsulation.



Reduces toxicity of the encapsulated agents.

Disadvantages 

Production cost is high



Leakage and fusion of encapsulated drug/molecules

iv.

BASED ON COMPOSITION AND MODE OF DELIVERY

TYPE

COMPOSITION

Conventional Liposomes

Neutral or negatively charged Subject phospholipids

CHARACTERISTICS to

coated-

and endocytosis;

cholesterol

ultimately

pit

contents delivered

to

lysosomes; short circulation half-life;

dose

dependent

pharmacokinetics pH sensitive Liposomes

Phospholipids such as PE or Subject

to

coated-

pit

DOPE with either CHEMS endocytosis and release their or OA

contents in cytoplasm; dose dependent pharmacokinetics

Cationic Liposomes

Cationic lipids with DOPE

Possibly fuse with cell or endosome suitable

membranes; for

delivery

negatively

of

charged

macromolecules(DNA, RNA, oligos) Long circulating Liposomes

PEG derivates

Hydrophilic surface coating; low opsonization

Immuno Liposomes

CL or LCL with attached Subject to receptor-mediated monoclonal

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antibody

or endocytosis;

cell

specific

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v.

binding

Based on structural parameters: Unilamellar vesicles

size

Small Unilamellar vesicles(SUV)

20-40 nm

Medium Unilamellar vesicles(MUV)

40-80 nm

large Unilamellar vesicles(LUV)

100-1000 nm



Uni lamellar vesicles



Oligolamellar vesicles(OLV): These are made up of 2-10 bilayers of lipids surrounding a large internal volume.



Multilamellar vesicles: They have several bi layers.

PREPARATION OF LIPOSOMES There are many ways of preparing lipososmes. Some of the important methods are: 1. Hydration of lipids in presence of solvent 2. Ultrasonication 3. French Pressure cell 4. Solvent injection method a) Ether injection method b) Ethanol injection 5. Detergent removal Detergent can be removed by a) Dialysis b) Column chromatography c) Bio-beads 6. Reverse phase evaporation technique 7. High pressure extrusion 8. Miscellaneous methods a) Removal of Chaotropic ion b) Freeze-Thawing

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CHARACTERISATION OF LIPOSOMES: Broadly classified into three categories:  Physical characterisation: evaluates parameters including size, Shape, surface features, lamellarity, phase behaviour and drug release profile.  Chemical characterisation includes those studies which establish the purity, potency of various lipophilic constituents.  Biological characterisation establishes the safety and suitability of formulation for therapeutic application. vi.

CHARACTERISATION PARAMETER

TECHNIQUE

Vesicle shape

Electron microscopy

Lamellarity

Freeze fracture electron microscopy, p-31 Nuclear magnetic resonance spectroscopy.

Vesicle size and distribution

Light microscopy, fluorescent microscopy, Electron photon

microscopy, correlation

laser

scattering

spectroscopy,

gel

permeation technique Surface

morphology

and

size

of Cryo- transmission electron microscopy.

vesicles Encapsulation efficiency

Mini

column

centrifugation

method,

protamine aggregation method Phase

response

and

transitional Freeze

fracture

electron

microscopy,

behaviour

differential scanning calorimetry

Drug release

Invitro diffusion cell

vii. APPLICATIONS Applications of Liposomes in the sciences Discipline

Application

Mathematics

Topology of two-dimensional surfaces in three-dimensional space governed only by bilayer elasticity

Physics

Aggregation behaviour, fractals, soft and high-strength materials

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World Journal of Pharmacy and Pharmaceutical Sciences Permeability, phase transitions in two-dimensions, photo physics

Physical Chemistry

Colloid behaviour in a system of well-defined physical characteristics, inter and intra-aggregate forces, DLVO

Chemistry

Photochemistry, artificial photosynthesis, catalysis, micro compartmentalization

Biochemistry

Reconstitution of membrane proteins

into artificial

membranes Biology

Model biological membranes, cell function, fusion, recognition

viii.

Pharmaceutics

Studies of drug action

Medicine

Drug-delivery and medical diagnostics, gene therapy

Liposomes in the pharmaceutical industry

Liposome Utility

Current Applications

Disease States Treated

Solubilisation

Amphotericin B, minoxidil

Fungal infections

Site-Avoidance

Amphotericin B – reduced Fungal infections, cancer nephrotoxicity,

doxorubicin

– decreased cardiotoxicity Sustained-Release

Systemic

antineoplastic Cancer, bio therapeutics

drugs, hormones, corticosteroids, drug depot in the lungs Drug protection

Cytosine

arabinoside, Cancer

interleukins RES Targeting

Immuno

modulators, Cancer,

vaccines,

antimalarials, parasites

MAI,

tropical

macrophage-located diseases Specific Targeting

Cells

bearing

specific Wide

antigens Extra vasation

Leaky tumours,

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therapeutic

applicability vasculature

of Cancer, bacterial infections

inflammations,

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Accumulation

Prostaglandins

Cardiovascular diseases

Enhanced penetration

Topical vehicles

Dermatology

Drug depot

Lungs,

subcutaneous, Wide

intramuscular, ocular

therapeutic

applicability

MICROSPHERES Microspheres as carriers of drug become an approach of controlled release dosage form in novel drug delivery system. Microspheres are sometimes referred to as microparticles. Microspheres can be prepared from various natural and synthetic materials. Polymer microspheres, Glass microspheres and ceramic microspheres are commercially available. Polyethylene and polystyrene microspheres are two most common types of polymer microspheres. Advantages 

Microspheres provide constant and sustained therapeutic effect.



Improved drug utilisation through bioavailability and reduce the incidence or intensity of adverse effects.



Microsphere morphology provides a controllable variability in deprivation and drug release.



Dosing frequency is reduced and improves patient compliance.



Due to its spherical shape and smaller size they can be injected and smaller size.

Limitations 

The modified release from the formulations.



The release rate of the controlled release dosage form may vary from a variety of factors like food and the rate of transit though gut.



Differences in the release rate from one dose to another.



Controlled release formulations generally contain a higher drug load and thus any loss of integrity of the release characteristics of the dosage form may lead to potential toxicity.

TYPES OF MICROSPHERES  Bioadhesive microspheres: Adhesion of drug delivery device to the mucosal membrane such as, ocular, buccal, nasal, rectal etc., can be defined as bio adhesion. Microspheres

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exhibit a prolonged residence time at the site of application and causes intimate contact with the absorption site and produces better therapeutic action.  Magnetic microspheres: This kind of delivery system is very much important which localises the drug to the disease site. In this larger amount of freely circulating drug can be replaced by smaller amount of magnetically targeted drug. Magnetic carriers receive magnetic responses to a magnetic field from incorporated materials such as chitosan, dextran etc  Floating microspheres: In floating types the bulk density is less than the gastric fluid and so remains buoyant in stomach without affecting gastric emptying rate. The drug is released slowly at the desired rate. It also reduces chances of striking and dose dumping. It produces prolonged therapeutic effect and therefore reduces dosing frequencies.  Radioactive microspheres: radioactive microspheres deliver high radiation dose to the targeted areas without damaging the normal surrounding tissues. It differs from drug delivery system, as radio activity is not released from microspheres but acts from within a radioisotope typical distance and the different kinds of radioactive microspheres are α emitters, β emitters, γ emitters.  Polymeric microspheres: The different types of polymeric microspheres can be classified as follows and they are biodegradable polymeric microspheres and Synthetic polymeric microspheres.  Biodegradable polymeric microspheres: Biodegradable polymers prolongs the residence time when contact with mucous membrane due to its high degree of swelling property with aqueous medium , results gel formation. The rate and extent of drug release is controlled by concentration of polymer and the release pattern in a sustained manner.  Synthetic polymeric microspheres: The interest of synthetic polymeric microspheres are widely used in clinical application, moreover that also used as fillers, bulking agent, drug delivery vehicles, embolic particles etc and proved to be safe and biocompatible. PREPARATION OF MICROSPHERES Incorporation of solid, liquid or gases into one or more polymeric coatings can be done by micro encapsulation technique. The different methods used for various microspheres preparation depends on particle size, route of administration, duration of drug release and these above characters related to rpm, method of cross linking, drug of cross linking, evaporation time, co-precipitation etc. The various methods of preparations are

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1. Solvent evaporation method, a) Single emulsion technique. b) Double emulsion technique. 2. Coacervation phase separation method. 3. Spray drying and spray congealing method. 4. Polymerization method. I. Normal polymerization II. Interfacial polymerization. ix.

CHARACTERISATION

PARAMETER

TECHNIQUE

Particle size, shape, morphology

Conventional light microscopy, scanning electron microscopy, laser light scattering, multi size coulter counter

Surface chemistry of microspheres

Electron spectroscopy

Degradation of polymeric matrix of Fourier transform –infra red spectroscopy the carrier system Density

Multi volume pychnometer

Iso electric point

Micro electrophoresis

Capture efficiency

By allowing washed microspheres to lyse. The lysate subjected to determine active constituents as per monograph requirement %

entrapment

=

actual

content/

theoretical

content*100 Angle of contact

Measured by placing a droplet in a circular cell mounted above objective of inverted microscope

Invitro methods

Interface diffusion system- modified keshary Chien cell, dissolution apparatus

invivo methods

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Animal models

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APPLICATIONS 

Assay - Coated microspheres provide measuring tool in biology and drug research



Buoyancy - Hollow microspheres are used to decrease material density in plastics (Glass and polymer)



Spacers - Used in LCD screens to provide a precision spacing between glass panels (Glass)



Standards – mono disperse microspheres are used to calibrate particle sieves, and particle counting apparatus.



Retro reflective - added on top of paint used on roads and signs to increase night visibility of road stripes and signs (glass)



Thickening Agent - Added to paints and epoxies to modify viscosity and buoyancy

PHARMACEUTICAL APPLICATIONS Cancer research Controlled-Release Vaccines DNA Encapsulation Ophthalmic Drug Delivery Gene delivery Intra tumoral and local drug delivery Oral drug delivery Nasal drug delivery Buccal drug delivery Gastrointestinal drug delivery Per oral drug delivery Transdermal drug delivery Colonic drug delivery Diagnostic uses of radioactive microspheres: Thrombus imaging in deep vein thrombosis, Blood flow measurements, Liver and spleen imaging, Bone marrow imaging, Tumour imaging. MONOCLONAL ANTIBODIES Monoclonal antibody production by somatic cell fusion or hybridoma technology was introduced by Kolher and Milstein in 1975. The technique involves fusing a normal antibody producing B cell with a myeloma cell to produce a hybrid cell or hybridoma.

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 Monoclonal antibodies characteristics: Their ability to be produced in unlimited quantities, Specificity of binding, their homogeneity  Additionally, one unique advantage of hybridoma production is that impure antigens can be used to produce specific antibodies. PRODUCTION 1: Immunization of Mice and Selection of Mouse Donors for Generation of Hybridoma Cells 2: Screening of Mice for Antibody Production 3: Fusion of Myeloma Cells with Immune Spleen Cells 4: Selection of hybridoma cells 5: Checking for hybridoma cells 6: Cloning of Hybridoma Cell Lines APPLICATIONS Monoclonal antibodies are widely used as diagnostic and research reagents. They are used in diagnostic kits such as ELISA, Immuno fluorescence to diagnose various diseases.  Enumeration of human lymphocyte subpopulations, anti-CD3 identifies all mature T lymphocytes, anti-CD4 identifies helper T lymphocyte subset, and anti-CD8 identifies cytotoxic T lymphocyte subset.  Immuno suppression: anti-CD3 depresses T cell function and anti-CD4 induces tolerance.  Passive immunization: High titre antimicrobial human monoclonals can passive protection.  Blood grouping: anti-A monoclonal provides a more reliable standard reagent than conventional anti sera.  Diagnosis in cancer: Monoclonal anti-T acute lymphocytic leukaemia (ALL) allows differentiation from non TALL.  Imaging: Radioactive anti-carcino embryonic antigen used to localize colonic tumours or secondary metastases by scanning.  Treatment of cancers: monoclonal antibody is coupled to a strongly-radioactive atom, such as Iodine-131 to aid in killing the target cancer cells.  Purification of antigen: Isolate antigen from mixtures by monoclonal affinity chromatography.

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 Chimeric monoclonal antibodies, which contain human Fc portion, are more useful for human use. CONCLUSION It is very difficult for a drug molecule to reach its destination (site of action) in the complex cellular network of an organism. Nanotech targeted delivery of drug is becoming one of the brightest stars in the medical sciences. The inherent advantage of this technique has been reduction in the dose and the side effect of drug. The biological approach is more specific but it also has some limitations which may be overcome soon, keeping in mind the giant leaps taken by research scientists in the recent past. Nanotechnology in medicine is definitely here to stay. Liposomes have been realised as extremely useful carrier systems for targeted drug delivery. The use of lipososmes in the delivery of drugs and genes are promising and is sure to undergo further developments in future. Nanoparticles are one of the promising drug delivery systems, which can be of potential use in controlling and targeting drug delivery it is a frontier area of future scientific and technological development. Nanoparticles are used for parenteral, oral, ocular and transdermal applications as well as in cosmetics and hair technologies, sustained release formulations and as carrier for radio nucleotides in nuclear medicine. new nanoparticles production techniques and equipment will aid in further discovery of pharmaceutical drugs microspheres are better choice of drug delivery system than many other types of drug delivery system because it is having the advantage of target specificity and better patient compliance. Its applications are enormous as they are not only used for delivering drugs but also for imaging tumours, detecting bio molecular interaction etc. So in future microspheres will have an important role to play in the advancement of medicinal field. Monoclonal antibodies for drug targeting are progressing steadily toward increased clinical use. MAbs are also increasingly used in heart disease, multiple sclerosis, disorders of the immunological defense system, and viral, bacterial, and rickettsial infections. Since each MAb is directed against a single determinant, it attains a finer, more specific recognition of its antigen than conventional antibodies. Investigators have been using MAbs as exquisitely sensitive probes to guide drugs to target cells or organs. REFERENCES 1 Mrs Jaya Agnihotri, Dr. Shubhini Saraf, Dr. Anubha Khale, Targeting: New Potential carriers for Targetted Drug Delivery system, International Journal of pharmaceutical sciences Review and Research 2011;8(2):117-120.

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2 VJ Mohanraj, Y Chen, Nanoparticles – A Review, Tropical Journal of Pharmaceutical Research 2006; 5(1):561-564. 3 A.R. Mullaicharam, Nanoparticles in Drug Delivery systems, International Journal of Nutrition, Pharmacology, Neurological diseases 2011; 1(2):103-108. 4 Elvis A. Martis, Rewa R. Badve, Mukta D. Degwekar, Nanotechnology Based Devices and Applications in Medicine: An Overview 2013; 3(1):69-70. 5 Prabhakar Vishvakrama and Saurabh Sharma, Liposomes: An Overview, International Journal of Research in Pharmaceutical and Biomedical Sciences 2012; 3(3):1074-1076. 6 Kant Shashi, Kumar Satinder, Prashar Bharat, A Complete Review on Liposomes, International research Journal of Pharmacy 2012;3(7):10-15. 7 D.D. Lasic, Applications of Liposomes, Volume 1, edited by R. Lipowsky and E. Sackmann 493-494. 8 Prasanth v.v, Akash Chakraborthy Moy, Sam T Mathew, Rinku Mathapan, Microspheres An Overview, International Journal of Research in Pharmaceutical and Biomedical Sciences 2011;2(2):332-337. 9 Shagufta Khan, Tripti Tiwari, Neha Rao, Amit Joshi, Bal Krishna Dubey, Microspheres: A Review, World Journal of Pharmacy and Pharmaceutical Sciences 2012; 1(1):126129,139-142. 10 Kataria Sahil1, Middha Akanksha1, Sandhu Premjeet1, Ajay Bilandi and Bhawana Kapoor, Microsphere: A Review, International Journal of research in Pharmacy and Chemistry 2011; 1(4):1186-1188. 11 Peter A. Ward, Methods of Producing Monoclonal antibodies, 4-9.

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