Health and wellbeing
Targeted Routes of drug delivery

Targeted Routes of drug delivery

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Drug delivery in a selective manner to a biological target, such as an organ, tissue, cells, or intracellular organelles, is called targeted drug delivery. Targeted drug delivery is achieved by ensuring high drug concentration in a target organ or tissue through the systemic circulation. In other words, a drug is delivered systemically or is absorbed into the systemic circulation, first—before accumulating at the target site of action. This modality is exemplified by the intravenous administration of a liposomal delivery system of a cytotoxic drug such that the drug distribution into the kidney is avoided, thus minimizing the renal side effects of the drug.

This modality is distinguished from localized drug therapy, wherein the drug is not intended to reach systemic circulation. The drug is administered or applied locally for local action. This modality is exemplified by localized application of an antibiotic on a skin laceration or infection.

A third modality is the utilization of different organs or organ systems to enable drug absorption into the systemic circulation. For example, transdermal or sublingual drug delivery is intended for drug absorption into the systemic circulation.

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 development 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 addition, sometimes, targeted strategies are intended to avoid drug exposure to a specific organ or tissue

Oral drug delivery

The preferred route of administration for pharmaceutical products has been oral ingestion. As a drug passes through the GI tract, it encounters different environments with respect to pH, enzymes, electrolytes, fluidity, and surface features, all of which can influence drug absorption. There is a great variation in the pH across the GI tract, which runs from the mouth to the anus. The interdigestive migration of a drug or a dosage form is governed by GI motility, wherein the drug is exposed to different pHs at different time periods.

The preferred route of administration for pharmaceutical products has been oral ingestion.

Apart from the pH, mucosal layer plays an important role in drug absorption from the lumen of the GI tract. Small intestine has large epithelial surface area, which consists of mucosa, villi, and microvilli. Drug must first diffuse through the unstirred aqueous layer, the mucous layer, and the glycocalyx (which is the coating of the mucous layer) in order to reach the microvilli, which is the apical cell membrane. The tight junction between the cell membranes of adjacent epithelial cells acts as a major barrier to the intercellular passage of drug molecules from the intestinal lumen to the lamina propria.

The low oral bioavailability of peptide and protein drugs is primarily due to their large molecular size and vulnerability to proteolytic degradation in the GI tract. Most protein and peptide drugs are susceptible to rapid degradation by digestive enzymes. Furthermore, most peptide and protein drugs are rather hydrophilic and thus are poorly partitioned into epithelial cell membranes, leading to their absorption across the GI tract through passive diffusion.

Buccal and sublingual drug delivery

The buccal and sublingual mucosae in the oral cavity provide an excellent alternative for the delivery of certain drugs. Oral transmucosal absorption is generally rapid because of the rich vascular supply to the mucosa. These routes provide improved delivery for certain drugs that are inactivated by first-pass intestinal/hepatic metabolism or by proteolytic enzymes in the GI tract.

The buccal and sublingual mucosae in the oral cavity provide an excellent alternative for the delivery of certain drugs.

The buccal mucosa is considerably less permeable than the sublingual area and is generally not able to provide rapid absorption properties. The buccal mucosa has an expanse of smooth muscle and relatively immobile mucosa, which makes it a more desirable region for retentive systems used for oral transmucosal drug delivery. Thus, the buccal mucosa is suitable for sustained delivery applications, delivery of less permeable molecules, and perhaps peptide drugs

Nasal drug delivery

Although nasal route is traditionally used for locally acting drugs, this route is getting more attention for the systemic delivery of various peptide drugs that are poorly absorbed via the oral route. The major advantages of nasal administration include the fast absorption, rapid onset of action, and avoidance of hepatic and intestinal first-pass effects. There are three major barriers to drug absorption across nasal mucosa. These include a physical barrier composed of the mucus and epithelium, a temporal barrier controlling the mucosal clearance, and an enzymatic barrier acting principally on protein and peptide drugs. The physical barrier consists of a lipoidal pathway and an aqueous pore pathway. Nasally administered drugs have to pass through the epithelial cell layer to reach the systemic circulation. Nasal absorption of weak electrolytes is dependent on the degree of ionization, with higher nasal absorption of a drug at a pH lower than its pKa.

Pulmonary drug delivery

The respiratory tract includes the nasal mucosa, hypopharynx, and large and small airway structures (trachea, bronchi, bronchioles, and alveoli). This tract provides a large mucosal surface for drug absorption. Lung epithelium is highly permeable and has low metabolic activity compared with the liver and intestine. With a large surface area and highly permeable membrane, alveolar epithelium permits rapid absorption. This route of administration is useful for treating pulmonary conditions and for drug delivery to other organs via the circulatory systems. In general, lipid- soluble molecules are absorbed rapidly from the respiratory tract, and thus, an increasing number of drugs is being administered by this route, including bronchodilators (e.g., beclometasone), corticosteroids, antibiotics, antifungal agents, antiviral agents, and vasoactive drugs.

This route of administration is useful for treating pulmonary conditions and for drug delivery to other organs via the circulatory systems.

Ocular drug delivery

Drugs are usually topically applied to the eyes in the form of drops or ointments for local action. Following topical administration, the drug is eliminated from the eye by nasolacrimal drainage, tear turnover, productive corneal absorption, and nonproductive conjunctival uptake. There are two barriers to ocular drug adsorption: (a) the blood–aqueous barrier and (b) the blood–retina barrier. The blood–aqueous barrier is composed of the ciliary epithelium, the epithelium of the posterior surface of the iris, and blood vessels within the iris. Drugs enter the aqueous humor at the ciliary epithelium and at blood vessels. Many substances are transported out of the vitreous humor at the retinal surface.

Rectal drug delivery

Rectal administration provides rapid absorption of many drugs and is an alternative when oral administration is inconvenient because of the inability to swallow or because of GI side effects such as nausea, vomiting, and irrigation. More importantly, rectal drug administration has the advantage of minimizing or avoiding hepatic first-pass metabolism. The rectal bioavailability of lidocaine in human is 65%, as compared with an oral bioavailability of 30%.

Rectal route is used to administer diazepam to children who are suffering from epileptics, in whom it is difficult to establish IV access

Rectal route is used to administer diazepam to children who are suffering from epileptics, in whom it is difficult to establish IV access. However, rectal administration of drugs is inconvenient and has irregular drug absorption. Moreover, rectal administration should be avoided in immunosuppressed patients in whom even minimal trauma could lead to the formation of an abscess.

Vaginal drug delivery

Vaginal epithelium is permeable to a wide range of substances, including steroids, prostaglandins, antibiotics, estrogens, and spermicidal agents. Most steroids are readily absorbed by vaginal epithelium, leading to their higher bioavailability compared with their oral administration, because of a reduced first-pass metabolism. For drugs with high membrane permeability, vaginal absorption is determined by permeability of the aqueous diffusion layer, whereas for drugs with low membrane permeability, such as testosterone and hydrocortisone, vaginal absorption is determined by membrane permeability. Vaginal ointments and creams contain drugs such as anti-infectives, estrogenic hormone substrates, and contraceptive agents. Contraceptive creams contain spermicidal agents and are used just before intercourse.

Vaginal ointments and creams contain drugs such as anti-infectives, estrogenic hormone substrates, and contraceptive agents.

 Parenteral drug administration

Most injections are designed for administration into a vein (intravenous, IV), into a muscle (intramuscular, IM), into the skin (intradermal, ID), or under the skin (subcutaneous, SC). Nevertheless, drugs may be administered into almost any organs or area in the body, including the joints  (intraarticular), joint fluid area (intrasynovial), spinal column  (intraspinal), spinal fluid (intrathecal), arteries (intraarterial), and in the heart  (intracardiac)

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