Drug delivery in a selective manner to a biological target, such as organ, tissue, cells, or intracellular organelles, is called targeted drug delivery.
Targeted drug
delivery
Drug
delivery in a selective manner to a biological target, such as organ, tissue,
cells, or intracellular organelles, is called targeted drug delivery. Targeted
drug delivery is differentiated from target-based drug develop-ment or drug
targets, which are defined as the molecular targets that the drugs modulate for
their pharmacological action. Drug therapy that aims to utilize drug molecules
that target a specific protein or receptor for their action is called targeted
drug therapy. Targeted drug delivery, on the other hand, refers to the science
and technology of presenting a drug to its site of action. The overall goal of
all drug-targeting strategies is the improvement of efficacy and/or safety
profile of a drug substance.
Targeted
drug delivery can involve either drug delivery to a specific organ or tissue or
avoiding drug delivery to a specific organ, tissue, or cells. Targeted drug
delivery to a particular physiological location can bring the drug to its
primary site of action. Thus, it can help improve the efficacy of a drug or prevent
its undesired toxicities in other tissues or organs. In addi-tion, sometimes,
targeted strategies are intended to avoid drug exposure to a specific organ or
tissue.1 This can help avoid specific drug-related toxici-ties in particular
organs, such as the kidney. For example, intravenous (IV) injection of
liposomal doxorubicin has lower nephrotoxicity and cardio-toxicity than IV
injection of doxorubicin solution.
The
most significant advantages of targeted drug delivery are realized in acute
disease states, for example, targeting cytotoxic anticancer drugs to a specific
organ (e.g., brain, lungs, liver, kidney, and colon) or the tumor tissue. For
example, prodrugs of doxorubicin have been prepared with folate ligand
conjugated through bovine serum albumin or polyethylene glycol (PEG), which
enable targeting of the drug to the tumors that express folate recep-tors. Two
important design elements of targeted DDSs are (a) the selection of the target
organ or tissue and (b) the selection of the targeting strategy.
·
The selection of target organ or tissue is governed by the
pharmacologi-cal need of the disease state and the drug substance. For example,
drugs are targeted to the blood–brain barrier (BBB) for drug delivery to the
brain for neurodegenerative diseases such as Alzheimer’s disease.
·
The selection of the targeting strategy for the DDS is
governed by the pathophysiology of the target tissue and how it can be utilized
to impart stimuli-responsive physicochemical property changes in the DDS. For
example, leaky vasculature of the tumor tissue can be uti-lized for passive
drug targeting by designing a DDS that is smaller in particle size and thus can
extravasate to the tumor site. In addition, expression of specific biochemical
receptors on cell surface of tumor tissues can be utilized for active targeting
of the DDS to tumor cells.
Several
drug-targeting approaches have successfully transitioned from the proof of
concept to the clinical application and have become a state of the art.
Examples of targeted drug delivery platforms that have become well accepted in
the clinical practice include the following:
·
Enteric coating of oral solid dosage forms to overcome
chemical insta-bility against acidic pH of the gastrointestinal (GI) tract or
adverse effects of the drug in the gastric environment
·
Pulmonary drug delivery by dry powder inhalation
·
Ocular inserts for drug delivery to the surface of the eye
·
Transdermal and implantable DDSs for sustained systemic
absorp-tion or local drug delivery.
In
addition, several drug delivery strategies being explored are at different
preclinical and clinical stages of advancement. Targeted delivery of small and
macromolecular drugs has been discussed in depth in a recent book.2 In this chapter, we will describe different
drug-targeting strategies and the role of physicochemical properties of the
DDS, combined with the disease mechanism and tissue physiology, in the
identification of target as well as a targeting strategy and vehicle.
The
design and development of targeted drug delivery agents are based on the
biological principles of physiological differences in target tissues compared
with other organs or tissues that can be utilized for targeting approaches.
These biological differences are matched to the physicochemi-cal principles of drug
release from the DDS that targets its drug cargo to a specific organ or tissue.
Such a DDS can be exemplified by the drug carriers that include
stimuli-responsive polymers that demonstrate a signif-icant change in their
properties with relatively minor change in an environ-mental physicochemical
stimulus. The environmental physicochemical or mechanical stimuli that can
cause response in the stimuli-responsive DDSs are exemplified by the following:
·
pH
·
Ionic strength or osmolarity
·
Light
·
Heat
·
Electricity
·
Ultrasound
·
Oxidation–reduction (redox) potential
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