INTRODUCTION:

Targeted drug delivery is a kind of smart drug delivery system which is miraculous in delivering the drug to a patient. This targeted drug delivery is a kind of intelligent drug delivery system that works miraculously in delivering the drug to a patient. This conventional drug delivery system occurs through the absorption of the drug through a biological membrane, while the targeted release system involves releasing the drug in a dosage form. The targeted drug delivery system is based on a process in which a specific amount of a therapeutic agent is delivered to a diseased target area in the body over an extended period of time. This helps maintain the required drug levels in plasma and tissues in the body; This will prevent the drug from damaging healthy tissue.

The drug delivery system is highly integrated and requires different disciplines such as chemists, biologists and engineers to join forces to optimize this system. When implementing a targeted delivery system, the following design criteria for the system must be considered: the drug properties, side effects of the drugs, the route taken for delivery of the drug, the target site, and the disease-based products such a delivery system is made considering the specific properties of target cells, the nature of markers or transporters or vehicles that deliver the drug to specific receptors and ligands, and physically modulated components. Ideally, targeted drug delivery systems should be biochemically inert (non-toxic), should be non-immunogenic, should be physically and chemically stable under in vivo and in vitro conditions, and should have and should have restricted drug distribution to target cells or tissues or organs capillary distribution. It should have a controllable and predictable rate of drug release and also the drug release should not affect drug action. It should have a therapeutic level of drug release and should exhibit minimal leakage of the drug during transport. Carriers used should be biodegradable or easily excreted from the body. The manufacture of the delivery system should be simple or reasonably simple, reproducible and cost effective. A targeted drug delivery system is preferred over conventional drug delivery systems for three main reasons. The first is pharmaceutical reason. Conventional drugs have low solubility and greater drug instability compared to targeted drug delivery systems. Conventional drugs also have poor absorption, a shorter half-life, and require a large volume of distribution. These constitute its pharmacokinetic properties^1,2.

TYPES OF TARGETED DRUG DELIVERY:

As mentioned earlier, targeting the drug to a specific area not only increases the therapeutic effectiveness of drugs, but also aims to reduce the toxicity associated with the drug to allow for lower doses of the drug for therapy. In order to meet such conditions, two approaches are pursued across the board.

Classification of drug:

Passive targeting:

It , to the accumulation of a drug or drug delivery system at a specific site, such as the B. an anticancer drug, the explanation of which can be attributed to physicochemical or pharmacological factors of the disease. Therefore, in the case of cancer treatment, the size and surface properties of drug delivery nanoparticles must be specifically controlled to maximize uptake by the reticulo-endothelial system (RES). Circulation times and targeting ability. The bottom line is passive targeting is a misnomer, which is a simple system for delivering drugs through the bloodstream. Drug release or drug effects are restricted to selected sites in the body, such as B. a tumor, but not the liver. Other examples include targeting antimalarial drugs to treat Leishmiansis, Brucellosis, Candiadsis⁸.

Active targeting:

Active targeting means a specific ligand-receptor interaction for intracellular localization that only occurs after blood circulation and extravasations. This active targeting approach can be further broken down into three different targeting levels

1. First order targeting refers to the restricted distribution of drug delivery systems to the capillary bed of a predetermined target site, organ or tissue, e.g. Compartmental targeting in lymphatics, peritoneal cavity, plural cavity, cerebral ventricles and eyes, joints.

2. Second-order targeting refers to the selective delivery of drugs to specific cell types, such as tumor cells, rather than normal cells, e.g. selective drug delivery to Kupffer cells in the liver.

3. Third order targeting refers to drug delivery specifically to the intracellular site of target cells, e.g. receptor-based ligand-mediated entry of a drug complex into a cell by endocytosis.

Fig. No. 1 Targeted Drug Dilvary System

Targeted drug delivery is a system for specifying the drug moiety directly into its target body area (organ, cellular and subcellular level of a specific tissue) in order to overcome the a specific toxic effect of conventional drug delivery and thereby reduce the amount of drug required for therapeutic efficacy. To achieve this goal, the Magic Bullet concept was developed, which led scientists to research for more than a century and led to the imagination of various nanometer-sized devices – today’s nanomedicine. Different carrier systems are used and investigated, including colloidal (vesicular and multiparticulate) carriers, polymers and cellular/subcellular systems. This overview looks at the need and benefits of targeting with its basic principles, strategies, and delivery systems. Current progress, challenges and future prospects are also highlighted. A targeted drug delivery system is a specialized form of drug delivery system in which the drug is selectively directed or delivered only to its site of action or absorption and not to the non-target organs, tissues or cells.

· This is a method of administering a drug to a patient in a way that increases the concentration of the drug in some parts of the body compared to others.

· Targeted drug delivery attempts to concentrate drug in the tissues of interest while reducing the relative concentration of drug in the remaining tissues.

· This improves effectiveness and reduces side effects.

THE DRUG MAY BE DELIVERED:

· To the capillary bed of active sites.

· On the specific cell type (or) even an intracellular region. Example: tumor cells but no normal cells.

· To a specific organ (or tissue) based on skin color where the wearer recognizes the target.

AIM:

· To achieve a desired pharmacological response at selected sites without undesired interactions at other sites, giving the drug a specific effect with minimal side effects and a better therapeutic index.

· Ex-In Cancer Chemotherapy and Enzyme Replacement Therapy.

REASON FOR TARGETING PHARMACEUTICALS:

· To treat or prevent diseases.

· Active ingredient instability in conventional dosage form Solubility, biopharmaceutically low absorption, high membrane binding, biological instability, pharmacokinetically/pharmacodynamically short half-life, large volume of distribution, low specificity, clinical, low therapeutic index.

6. IDEAL PROPERTIES:

· It should be non-toxic, biocompatible, biodegradable and physico-chemically stable in vivo and in vitro.

· Confine drug distribution to target cells, tissues or organs and exhibit uniform capillary distribution.

· Controllable and predictable rate of drug release.

· Drug release does not affect drug action.

· Therapeutic level of drug release.

· Minimal drug leakage during transport.

· The carriers used must be biodegradable or easily eliminated from the body and there must be no carrier-induced modulation of the disease state.

· Manufacturing of the delivery system should be simple or fairly simple, reproducible and inexpensive.^2,3

Advantage:

Drug administration protocols can be simplified.

· Toxicity is reduced by delivering a drug to its target site, thereby reducing harmful systemic effects.

· The drug can be administered in a smaller dose to achieve the desired effect.

· Avoidance of hepatic first-pass metabolism.

· Improving uptake of target molecules such as peptides and particles.

· The dose is lower compared to a traditional drug delivery system.

· No peak and valley plasma concentration.

· Selective targeting of infection cells that are similar to normal cells.⁴

DISADVANTAGE:

· Fast release of target systems.

· Immune reactions against intravenously administered carrier systems.

· Inadequate localization of target systems in tumor cells.

· Diffusion and redistribution of released drugs.

· Requires advanced technology for formulation.

· Requires knowledge of manufacturing, storage and management.

· Drug deposits at the target site can produce toxicity symptoms.

· Difficult to maintain dosage form stability^5,6

Targeting GIT:

A controlled drug delivery system currently involves controlling either the time or location of drug delivery. Controlling the time course of drug delivery is a more classical approach. Site-specific or targeted delivery involves drug delivery to a specific organ or class of cells or physiological compartment. Depending on the potential target site, various site-specific controlled-elease oral systems have been developed.

Classified as:

I. Systems targeted at stomach/duodenum

II. Systems targeted at small intestine

III. Systems targeted at lymphatic

IV. Systems targeted at colon

V. Systems targeted at stomach/duodenum

Such systems not only increase the residence time in the stomach, but in all areas of the gastrointestinal tract, so that the dissolved active ingredients reach their optimal absorption site and are ready for absorption. These types of systems

Used with:

· Drug insoluble in intestinal juice

· Medicines that develop their therapeutic effect in the stomach/duodenum, e.g. B. antacids such as oxides, hydroxides and carbonates of magnesium, aluminum hydroxides and magnesium trisilicate.

1. Drugs showing site-specific absorption from the duodenum, e.g. B. chlorpheniramine maleate.

2. Drugs that are extensively absorbed from the stomach, e.g. B. Certain vitamins (Vit. B, Vit. C) and minerals.

3. Drugs that failed other conventional sustained release systems have achieved satisfactory results with these systems, e.g. B. chlordiazepoxide.

4. Strongly acidic drugs, e.g. aspirin, cause irritation when they come into contact with the stomach wall, which can be prevented in this way

Types of systems:

Systems targeted at small intestine These systems are made such that they permit the safe Passage of a system through the acid environment of the Stomach to mare suitable juices of the intestine.

These types of systems are used with:

1. Drugs destroyed by gastric acid e.g., enzymes.

2. Drugs irritating to gastric mucosa. E.g., sodium salicylate.^7,8

Targeting the respiratory tract:

Targeting drugs to the airways has been attempted, with bronchodilators and anti-inflammatory steroids used to effectively control asthma. The nasal or pulmonary route of drug administration delivers therapeutic agents to the diseased region while reducing their distribution to other organs. Thus, it is evident that a better therapeutic index for the treatment of respiratory diseases can be obtained when drugs are administered directly to the respiratory tract. Drug delivery through the airways has been used for local and systemic effects.

These systems are used for the following purposes:

1. Avoidance of hepatic first pass metabolism.

2. Rapid onset of action.

3. Better patient compliance.

4. Enhancement of bioavailability.

5. Peptide and proteins drug moieties.

Targeting the brain:-

The blood-brain barrier (BBB) is a uniquely protective barrier. It provides a very efficient exclusion of a variety of blood-borne compounds from the brain by impeding the free flow of blood between the brain and the rest of the body. This also prevents the ingress of hydrophilic compounds such as various neurotransmitters, amino acids etc. unless they are transported to the brain by an active transport system. This realization that the BBB should act as a barrier to the efflux of hydrophilic molecules formed in situ has led to the development of brain targeting to drugs through a redox chemical delivery system to allow drug targeting to the brain for substrate drugs that may be of great importance. Ex-dopamine was delivered using the N1-substituted dihydropyridine pyridine salt type redox system. This drug-carrier complex was sufficiently lipophilic to be distributed throughout the body after intravenous administration. The lipophilic drug-carrier complex had to undergo sequential hydrolytic and oxidative transformations at the redox-carrier part to finally generate the prodrug, which upon further cleavage led to the release of dopamine in the brain.^9,10

Fig No.2. Need of Targeted Drug Delivery

Properties of targeted drug delivery:

It should be non-toxic, biodegradable, biocompatible, and physicochemically stable in vivo and in vitro, and should restrict drug delivery to target cells or tissue or organ, or should exhibit uniform capillary distribution. Predictable and controllable and rate of drug release. Drug release should not affect drug delivery. Therapeutic level of drug release. Minimal drug leakage during transport. The carrier used should be biodegradable or readily excreted from the body, and no carrier should induce modulation of the disease state¹¹

CONCLUSIONS:

Targeted drug delivery technology has become an important tool in cancer therapy research to reduce drug side effects. Drug carriers can be synthesized from different types of materials, including polymer nanoparticles, inorganic nanoparticles, and polymer/inorganic nanocomposites with different morphologies. Factors affecting the effectiveness of nanoparticles for chemotherapy delivery systems and the properties of ideal nanoparticles have been discussed. Assess the physicochemical properties of drug delivery in accordance with their corresponding therapeutic efficacy against different cancer cell lines, as well as the beneficial medical performance of each drug carrier to determine the most targeted site of action. On the other hand, the challenges of nanomedicine in oncology specifically targeted the brain, breast and lungs.

REFERENCE:

1. https://www.researchgate.net/publication/265862863_A_Review_on_Targeted_Drug_Delivery_Its_Entire_Focus_on_Advanced_Therapeutics_and_Diagnostics

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6. https://www.sciencedirect.com/science/article/abs/pii/S1773224721001064

7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275483/#:~:text=Targeted%20drug%20delivery%20is%20a,drug%20required%20for%20therapeutic%20efficacy.

8. https://www.slideshare.net/anushanagraj/targeted-drug-delivery-system

9. https://www.researchgate.net/publication/292926440_Targeted_drug_delivery_systems

10. https://www.researchgate.net/publication/319122405_TARGETED_Drug_Delivery-A_Review

11. https://www.sciencedirect.com/topics/pharmacology-toxicology-and-pharmaceutical-science/targeted-drug-delivery

Received on 10.10.2022 Modified on 15.11.2022

Asian J. Res. Pharm. Sci. 2023; 13(1):45-48.

DOI: 10.52711/2231-5659.2023.00008