Targeted drug delivery
Encyclopedia
Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration
of the medication in some parts of the body relative to others. 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 is when the drug is released in a dosage form. 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 drug side effect
s, 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. Therefore, avoiding any damage to the healthy tissue via the drug. The drug delivery system is highly integrated and requires various disciplines, such as chemists, biologist and engineers, to join forces to optimize this system.
systems such as oral ingestion or intravascular injection, the medication is distributed throughout the body through the systemic blood circulation. For most therapeutic agents, only a small portion of the medication reaches the organ to be affected. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. For example, by avoiding the host's defense mechanisms and inhibiting non-specific distribution in the liver and spleen , a system can reach the intended site of action in higher concentrations. Targeted delivery is believed to improve efficacy
while reducing side effects.
When implementing a targeted release system, the following design criteria for the system need to taken into account: the drug properties, side effects of the drugs, the route taken for the delivery of the drug, the targeted site, and the disease.
Increasing developments to novel treatments requires a controlled microenvironment that is only accomplished through the implementation of therapeutic agents whose side effects can be avoided with targeted drug delivery. Advances in the field of targeted drug delivery to cardiac tissue will be an integral component to regenerate cardiac tissue.
There are two kinds of targeted drug delivery, active targeted drug delivery, such as some antibody
medications; and passive targeted drug delivery, such as the enhanced permeability and retention effect
(EPR-effect).
The most common vehicle currently used for targeted drug delivery is the liposome
. Liposomes are non-toxic, non-hemolytic and non-immunogenic even upon repeated injections; they are biocompatible and biodegradable and can be designed to avoid clearance
mechanisms (reticuloendothelial system (RES), renal clearance, chemical or enzymatic inactivation, etc.)Lipid based, ligand coated nanocarriers
can store their payload in the hydrophobic shell or the hydrophilic interior depending on the nature of the drug/contrast agent being carried.
The only problem to using liposomes in vivo is their immediate uptake and clearance by the RES system and their relatively low stability
in vitro. To combat this, polyethylene glycol
(PEG) can be added to the surface of the liposomes. Increasing the mole percent of PEG on the surface of the liposomes by 4-10% significantly increased circulation time in vivo from 200 to 1000 minutes.
s. They are prepared from certain amphiphilic co-polymers consisting of both hydrophilic and hydrophobic monomer units. They can be used to carry drugs that have poor solubility. This method offers little in the terms of size control or function malleability. Techniques have been developed that utilize reactive polymers along with a hydrophobic additive to produce a larger micelle
which create a range of sizes .
Dendrimer
s are also polymer-based delivery vehicles. They have a core that branches out in regular intervals to form a small, spherical and very dense nanocarrier.
, endothelial selectin (E-selectin
) and ICAM-1
have been found to adhere to inflamed endothelium
. Therefore the use of biodegradable particles can be also be used for cardiac tissue.
in constructing artificially designed
nanostructures out of nucleic acid
s such as DNA
, combined with the demonstration of systems for DNA computing
, has led to speculation that artificial nucleic acid nanodevices can be used to target drug delivery based upon directly sensing its environment. These methods make use of DNA solely as a structural material and a chemical, and do not make use of its biological role as the carrier of genetic information. Nucleic acid logic circuits have been demonstrated that could potentially be used as the core of a system which releases a drug only in response to a stimulus such as a specific mRNA. Additionally, a DNA "box" with a controllable lid has been synthesized using the DNA origami
method. This structure could encapsulate a drug in its close state, and open to release it only in response to a desired stimulus.
is to treat cancerous tumors.
The American Heart Association rates cardiovascular disease as the number one cause of death in the United States. Each year 1.5 million myocardial infarctions (MI) also known as heart attacks occur in the United States with 500,000 leading to deaths. The costs related to heart attacks exceed $60 billion per year. Therefore, there is a need to come up with an optimum recovery system. The key to solving this problem lies in the effective use of pharmaceutical drugs that can be targeted directly to the diseased tissue. This technique can help develop many more regenerative techniques
to cure various diseases. The development of a number of regenerative strategies in recent years for curing heart disease represents a paradigm shift away from conventional approaches which aim to manage heart disease.
Stem cell therapy can be used to help regenerate myocardium tissue and return the contractile function of the heart be creating/supporting a microenvironment before the MI. Developments in targeted drug delivery to tumors have provided the groundwork for the burgeoning field of targeted drug delivery to cardiac tissue. Recent developments have shown that there are different endothelial surfaces in tumors which has led to the concept of endothelial cell adhesion
molecule mediated targeted drug delivery to tumors.
Dose (biochemistry)
A dose is a quantity of something that may impact an organism biologically; the greater the quantity, the larger the dose. In nutrition, the term is usually applied to how much of a specific nutrient is in a person's diet or in a particular food, meal, or dietary supplement...
of the medication in some parts of the body relative to others. The goal of a targeted drug delivery
Drug delivery
Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well...
system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system
Route of administration
A route of administration in pharmacology and toxicology is the path by which a drug, fluid, poison, or other substance is taken into the body.-Classification:Routes of administration are usually classified by application location...
is the absorption of the drug across a biological membrane
Biological membrane
A biological membrane or biomembrane is an enclosing or separatingmembrane that acts as a selective barrier, within or around a cell. It consists of a lipid bilayer with embedded proteins that may constitute close to 50% of membrane content...
, whereas the targeted release system is when the drug is released in a dosage form. 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 drug side effect
Side effect
In medicine, a side effect is an effect, whether therapeutic or adverse, that is secondary to the one intended; although the term is predominantly employed to describe adverse effects, it can also apply to beneficial, but unintended, consequences of the use of a drug.Occasionally, drugs are...
s, 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. Therefore, avoiding any damage to the healthy tissue via the drug. The drug delivery system is highly integrated and requires various disciplines, such as chemists, biologist and engineers, to join forces to optimize this system.
Background
In traditional drug deliveryDrug delivery
Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well...
systems such as oral ingestion or intravascular injection, the medication is distributed throughout the body through the systemic blood circulation. For most therapeutic agents, only a small portion of the medication reaches the organ to be affected. Targeted drug delivery seeks to concentrate the medication in the tissues of interest while reducing the relative concentration of the medication in the remaining tissues. For example, by avoiding the host's defense mechanisms and inhibiting non-specific distribution in the liver and spleen , a system can reach the intended site of action in higher concentrations. Targeted delivery is believed to improve efficacy
Efficacy
Efficacy is the capacity to produce an effect. It has different specific meanings in different fields. In medicine, it is the ability of an intervention or drug to reproduce a desired effect in expert hands and under ideal circumstances.- Healthcare :...
while reducing side effects.
When implementing a targeted release system, the following design criteria for the system need to taken into account: the drug properties, side effects of the drugs, the route taken for the delivery of the drug, the targeted site, and the disease.
Increasing developments to novel treatments requires a controlled microenvironment that is only accomplished through the implementation of therapeutic agents whose side effects can be avoided with targeted drug delivery. Advances in the field of targeted drug delivery to cardiac tissue will be an integral component to regenerate cardiac tissue.
There are two kinds of targeted drug delivery, active targeted drug delivery, such as some antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
medications; and passive targeted drug delivery, such as the enhanced permeability and retention effect
Enhanced Permeability and Retention effect
The Enhanced Permeability and Retention effect is the property by which certain sizes of molecules tend to accumulate in tumor tissue much more than they do in normal tissues...
(EPR-effect).
Delivery vehicles
There are different types of drug delivery vehicles, such as, polymeric micelles, liposomes, lipoprotein-based drug carriers, nano-particle drug carriers, dendrimers etc. An ideal drug delivery vehicle must be non-toxic, biocompatible, non-immunogenic, biodegradable and avoid recognition by the host's defense mechanisms[3].Liposomes
Liposome
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 are composite structures made of phospholipids and may contain small amounts of other molecules...
. Liposomes are non-toxic, non-hemolytic and non-immunogenic even upon repeated injections; they are biocompatible and biodegradable and can be designed to avoid clearance
Clearance (medicine)
In medicine, the clearance is a measurement of the renal excretion ability. Although clearance may also involve other organs than the kidney, it is almost synonymous with renal clearance or renal plasma clearance. Each substance has a specific clearance that depends on its filtration characteristics...
mechanisms (reticuloendothelial system (RES), renal clearance, chemical or enzymatic inactivation, etc.)Lipid based, ligand coated nanocarriers
Nanomedicine
Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology. Current problems for nanomedicine involve understanding the issues related...
can store their payload in the hydrophobic shell or the hydrophilic interior depending on the nature of the drug/contrast agent being carried.
The only problem to using liposomes in vivo is their immediate uptake and clearance by the RES system and their relatively low stability
Chemical stability
Chemical stability when used in the technical sense in chemistry, means thermodynamic stability of a chemical system.Thermodynamic stability occurs when a system is in its lowest energy state, or chemical equilibrium with its environment. This may be a dynamic equilibrium, where individual atoms...
in vitro. To combat this, polyethylene glycol
Polyethylene glycol
Polyethylene glycol is a polyether compound with many applications from industrial manufacturing to medicine. It has also been known as polyethylene oxide or polyoxyethylene , depending on its molecular weight, and under the tradename Carbowax.-Available forms:PEG, PEO, or POE refers to an...
(PEG) can be added to the surface of the liposomes. Increasing the mole percent of PEG on the surface of the liposomes by 4-10% significantly increased circulation time in vivo from 200 to 1000 minutes.
Micelles and dendrimers
Another type of drug delivery vehicle used is polymeric micelleMicelle
A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single tail regions in the micelle centre. This phase is...
s. They are prepared from certain amphiphilic co-polymers consisting of both hydrophilic and hydrophobic monomer units. They can be used to carry drugs that have poor solubility. This method offers little in the terms of size control or function malleability. Techniques have been developed that utilize reactive polymers along with a hydrophobic additive to produce a larger micelle
Micelle
A micelle is an aggregate of surfactant molecules dispersed in a liquid colloid. A typical micelle in aqueous solution forms an aggregate with the hydrophilic "head" regions in contact with surrounding solvent, sequestering the hydrophobic single tail regions in the micelle centre. This phase is...
which create a range of sizes .
Dendrimer
Dendrimer
Dendrimers are repetitively branched molecules. The name comes from the Greek word "δένδρον" , 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...
s are also polymer-based delivery vehicles. They have a core that branches out in regular intervals to form a small, spherical and very dense nanocarrier.
Biodegradable particles
Biodegradable particles have the ability to target diseased tissue as well as deliver their payload as a controlled release therapy. Biodegradable particles bearing ligands to P-selectinP-selectin
P-selectin is a cell adhesion molecule on the surfaces of activated endothelial cells, which line the inner surface of blood vessels, and activated platelets...
, endothelial selectin (E-selectin
E-selectin
E-selectin, also known as CD62 antigen-like family member E , endothelial-leukocyte adhesion molecule 1 , or leukocyte-endothelial cell adhesion molecule 2 , is a cell adhesion molecule expressed only on endothelial cells activated by cytokines. Like other selectins, it plays an important part in...
) and ICAM-1
ICAM-1
ICAM-1 also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. This gene encodes a cell surface glycoprotein which is typically expressed on endothelial cells and cells of the immune system...
have been found to adhere to inflamed endothelium
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
. Therefore the use of biodegradable particles can be also be used for cardiac tissue.
Artificial DNA nanostructures
The success of DNA nanotechnologyDNA nanotechnology
DNA nanotechnology is a branch of nanotechnology which uses the molecular recognition properties of DNA and other nucleic acids to create designed, artificial structures out of DNA for technological purposes. In this field, DNA is used as a structural material rather than as a carrier of genetic...
in constructing artificially designed
Nucleic acid design
Nucleic acid design is the process of generating a set of nucleic acid base sequences that will associate into a desired conformation. Nucleic acid design is central to the fields of DNA nanotechnology and DNA computing...
nanostructures out of nucleic acid
Nucleic acid
Nucleic acids are biological molecules essential for life, and include DNA and RNA . Together with proteins, nucleic acids make up the most important macromolecules; each is found in abundance in all living things, where they function in encoding, transmitting and expressing genetic information...
s such as DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
, combined with the demonstration of systems for DNA computing
DNA computing
DNA computing is a form of computing which uses DNA, biochemistry and molecular biology, instead of the traditional silicon-based computer technologies. DNA computing, or, more generally, biomolecular computing, is a fast developing interdisciplinary area...
, has led to speculation that artificial nucleic acid nanodevices can be used to target drug delivery based upon directly sensing its environment. These methods make use of DNA solely as a structural material and a chemical, and do not make use of its biological role as the carrier of genetic information. Nucleic acid logic circuits have been demonstrated that could potentially be used as the core of a system which releases a drug only in response to a stimulus such as a specific mRNA. Additionally, a DNA "box" with a controllable lid has been synthesized using the DNA origami
DNA origami
DNA origami is the nanoscale folding of DNA to create arbitrary two and three dimensional shapes at the nanoscale. The specificity of the interactions between complementary base pairs make DNA a useful construction material through design of its base sequences...
method. This structure could encapsulate a drug in its close state, and open to release it only in response to a desired stimulus.
Applications
Targeted drug delivery can be used to treat many diseases, such as the cardiovascular diseases and diabetes. However, the most important application of targeted drug deliveryDrug delivery
Drug delivery is the method or process of administering a pharmaceutical compound to achieve a therapeutic effect in humans or animals. Drug delivery technologies modify drug release profile, absorption, distribution and elimination for the benefit of improving product efficacy and safety, as well...
is to treat cancerous tumors.
The American Heart Association rates cardiovascular disease as the number one cause of death in the United States. Each year 1.5 million myocardial infarctions (MI) also known as heart attacks occur in the United States with 500,000 leading to deaths. The costs related to heart attacks exceed $60 billion per year. Therefore, there is a need to come up with an optimum recovery system. The key to solving this problem lies in the effective use of pharmaceutical drugs that can be targeted directly to the diseased tissue. This technique can help develop many more regenerative techniques
Regenerative medicine
Regenerative medicine is the "process of replacing or regenerating human cells, tissues or organs to restore orestablish normal function". This field holds the promise of regenerating damaged tissues and organs in the body by replacing damaged tissue and/or by stimulating the body's own repair...
to cure various diseases. The development of a number of regenerative strategies in recent years for curing heart disease represents a paradigm shift away from conventional approaches which aim to manage heart disease.
Stem cell therapy can be used to help regenerate myocardium tissue and return the contractile function of the heart be creating/supporting a microenvironment before the MI. Developments in targeted drug delivery to tumors have provided the groundwork for the burgeoning field of targeted drug delivery to cardiac tissue. Recent developments have shown that there are different endothelial surfaces in tumors which has led to the concept of endothelial cell adhesion
Cell adhesion
Cellular adhesion is the binding of a cell to a surface, extracellular matrix or another cell using cell adhesion molecules such as selectins, integrins, and cadherins. Correct cellular adhesion is essential in maintaining multicellular structure...
molecule mediated targeted drug delivery to tumors.