Drug delivery

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A nasal spray bottle being demonstrated. Action photo of nasal spray on a black background.jpg
A nasal spray bottle being demonstrated.

Drug delivery refers to approaches, formulations, manufacturing techniques, storage systems, and technologies involved in transporting a pharmaceutical compound to its target site to achieve a desired therapeutic effect. [1] [2] Principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity are used to optimize efficacy and safety, and to improve patient convenience and compliance. [3] [4] Drug delivery is aimed at altering a drug's pharmacokinetics and specificity by formulating it with different excipients, drug carriers, and medical devices. [3] [5] [6] There is additional emphasis on increasing the bioavailability and duration of action of a drug to improve therapeutic outcomes. [7] Some research has also been focused on improving safety for the person administering the medication. For example, several types of microneedle patches have been developed for administering vaccines and other medications to reduce the risk of needlestick injury. [4] [8]

Contents

Drug delivery is a concept heavily integrated with dosage form and route of administration, the latter sometimes being considered part of the definition. [9] While route of administration is often used interchangeably with drug delivery, the two are separate concepts. Route of administration refers to the path a drug takes to enter the body, [10] whereas drug delivery also encompasses the engineering of delivery systems and can include different dosage forms and devices used to deliver a drug through the same route. [11] Common routes of administration include oral, parenteral (injected), sublingual, topical, transdermal, nasal, ocular, rectal, and vaginal, however, drug delivery is not limited to these routes and there may be several ways to deliver medications through other routes. [12]

Since the approval of the first controlled-release formulation in the 1950s, research into new delivery systems has been progressing, as opposed to new drug development which has been declining. [13] [14] [15] Several factors may be contributing to this shift in focus. One of the driving factors is the high cost of developing new drugs. A 2013 review found the cost of developing a delivery system was only 10% of the cost of developing a new pharmaceutical. [16] A more recent study found the median cost of bringing a new drug to market was $985 million in 2020, but did not look at the cost of developing drug delivery systems. [17] Other factors that have potentially influenced the increase in drug delivery system development may include the increasing prevalence of both chronic and infectious diseases, [15] [18] as well as a general increased understanding of the pharmacology, pharmacokinetics, and pharmacodynamics of many drugs. [3]

Current efforts

Current efforts in drug delivery are vast and include topics such as controlled-release formulations, targeted delivery, nanomedicine, drug carriers, 3D printing, and the delivery of biologic drugs. [19] [20]

The relation between nanomaterial and drug delivery

Nanotechnology is a broad field of research and development that deals with the manipulation of matter at the atomic or subatomic level. It is used in fields such as medicine, energy, aerospace engineering, and more. One of the applications of nanotechnology is in drug delivery. This is a process by which nanoparticles are used to carry and deliver drugs to a specific area in the body. There are several advantages of using nanotechnology for drug delivery, including precise targeting of specific cells, increased drug potency, and lowered toxicity to the cells that are targeted. Nanoparticles can also carry vaccines to cells that might be hard to reach with traditional delivery methods. However, there are some concerns with the use of nanoparticles for drug delivery. Some studies have shown that nanoparticles may contribute to the development of tumors in other parts of the body. There is also growing concern that nanoparticles may have harmful effects on the environment. Despite these potential drawbacks, the use of nanotechnology in drug delivery is still a promising area for future research. [21]

Targeted delivery

Targeted drug delivery is the delivery of a drug to its target site without having an effect on other tissues. [22] Interest in targeted drug delivery has grown drastically due to its potential implications in the treatment of cancers and other chronic diseases. [23] [24] [25] In order to achieve efficient targeted delivery, the designed system must avoid the host's defense mechanisms and circulate to its intended site of action. [26] A number of drug carriers have been studied to effectively target specific tissues, including liposomes, nanogels, and other nanotechnologies. [20] [23] [27]

Controlled-release formulations

Controlled or modified-release formulations alter the rate and timing at which a drug is liberated, in order to produce adequate or sustained drug concentrations. [28] The first controlled-release (CR) formulation that was developed was Dexedrine in the 1950s. [13] This period of time saw more drugs being formulated as CR, as well as the introduction of transdermal patches to allow drugs to slowly absorb through the skin. [29] Since then, countless other CR products have been developed to account for the physiochemical properties of different drugs, such as depot injections for antipsychotics and sex hormones that require dosing once every few months. [30] [31]

Since the late 1990s, most of the research around CR formulations has been focused on implementing nanoparticles to decrease the rate of drug clearance. [13] [29]

Modulated drug release and zero-order drug release

Many scientists worked to create oral formulations that could maintain a constant drug level because of the ability of drug release at a zero-order rate.blood's concentration. However, a few physiological restrictions made it challenging to create such oral formulations. First, because the lower parts of the intestine have a decreased capacity for absorption, the medication absorption typically declines as an oral formulation moves from the stomach to the intestine. The decreased drug amount released from the formulation over time frequently made this condition worse. Phenylpropanolamine HCl release from was the only instance of sustaining consistent blood concentration for roughly 16 hours. [32]

Delivery of biologic drugs

Pharmaceutical preparations containing peptides, proteins, antibodies, genes, or other biologic components often face absorption issues due to their large sizes or electrostatic charges, and may be susceptible to enzymatic degradation once they have entered the body. [3] [11] For these reasons, recent efforts in drug delivery have been focused on methods to avoid these issues through the use of liposomes, nanoparticles, fusion proteins, protein-cage nanoparticles, exploiting routes for the delivery of biologicals that toxins use and many others. [3] [33] [34] [35] [36] Intracellular delivery of macromolecules by chemical carriers is most advanced for RNA, as known from RNA-based COVID-19 vaccines, while proteins have also been delivered into cells in vivo and DNA is routinely delivered in vitro. [37] [38] [39] Among the various routes of administration the oral route is most favored by patients. For most biologic drugs, however, oral bioavailability is too low to reach a therapeutic level. Advanced delivery systems such as formulations containing permeation enhancers or enzyme inhibitors, lipid-based nanocarriers and microneedles will likely enhance oral bioavailability of these drugs sufficiently. [40] [41]

Nanoparticle drug delivery

Drug delivery systems have been around for many years, but there are a few recent applications of drug delivery that warrant 1. Drug delivery to the brain: Many drugs can be harmful when administered systemically; the brain is very sensitive to medications and can easily cause damage if a drug is administered directly into the bloodstream. As new drug formulations are being developed for brain diseases, including Alzheimer's disease and Parkinson's disease, researchers are working on ways to deliver drugs into the brain that do not cause damage to healthy tissue. For example, scientists have developed nanoparticles that can cross the protective blood-brain barrier and deliver drugs directly to the brain. [42] [43]

See also

Related Research Articles

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.

<span class="mw-page-title-main">Liposome</span> Composite structures made of phospholipids and may contain small amounts of other molecules

A liposome is a small artificial vesicle, spherical in shape, having at least one lipid bilayer. Due to their hydrophobicity and/or hydrophilicity, biocompatibility, particle size and many other properties, liposomes can be used as drug delivery vehicles for administration of pharmaceutical drugs and nutrients, such as lipid nanoparticles in mRNA vaccines, and DNA vaccines. Liposomes can be prepared by disrupting biological membranes.

<span class="mw-page-title-main">Transdermal patch</span> Adhesive patch used to deliver medication through the skin

A transdermal patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and into the bloodstream. An advantage of a transdermal drug delivery route over other types of medication delivery is that the patch provides a controlled release of the medication into the patient, usually through either a porous membrane covering a reservoir of medication or through body heat melting thin layers of medication embedded in the adhesive. The main disadvantage to transdermal delivery systems stems from the fact that the skin is a very effective barrier; as a result, only medications whose molecules are small enough to penetrate the skin can be delivered by this method. The first commercially available prescription patch was approved by the U.S. Food and Drug Administration in December 1979. These patches administered scopolamine for motion sickness.

<span class="mw-page-title-main">Dendrimer</span> Highly ordered, branched polymeric molecule

Dendrimers are highly ordered, branched polymeric molecules. Synonymous terms for dendrimer include arborols and cascade molecules. Typically, dendrimers are symmetric about the core, and often adopt a spherical three-dimensional morphology. The word dendron is also encountered frequently. A dendron usually contains a single chemically addressable group called the focal point or core. The difference between dendrons and dendrimers is illustrated in the top figure, but the terms are typically encountered interchangeably.

<span class="mw-page-title-main">Nanobiotechnology</span> Intersection of nanotechnology and biology

Nanobiotechnology, bionanotechnology, and nanobiology are terms that refer to the intersection of nanotechnology and biology. Given that the subject is one that has only emerged very recently, bionanotechnology and nanobiotechnology serve as blanket terms for various related technologies.

<span class="mw-page-title-main">Transdermal</span> Method of drug administration

Transdermal is a route of administration wherein active ingredients are delivered across the skin for systemic distribution. Examples include transdermal patches used for medicine delivery. The drug is administered in the form of a patch or ointment that delivers the drug into the circulation for systemic effect.

<span class="mw-page-title-main">Lipid-based nanoparticle</span> Novel drug delivery system

Lipid-based nanoparticles are very small spherical particles composed of lipids. They are a novel pharmaceutical drug delivery system, and a novel pharmaceutical formulation. There are many subclasses of lipid-based nanoparticles such as: lipid nanoparticles (LNPs), solid lipid nanoparticles (SLNs), and nanostructured lipid carriers (NLCs).

Buccal administration is a topical route of administration by which drugs held or applied in the buccal area diffuse through the oral mucosa and enter directly into the bloodstream. Buccal administration may provide better bioavailability of some drugs and a more rapid onset of action compared to oral administration because the medication does not pass through the digestive system and thereby avoids first pass metabolism. Drug forms for buccal administration include tablets and thin films.

Nanoparticles for drug delivery to the brain is a method for transporting drug molecules across the blood–brain barrier (BBB) using nanoparticles. These drugs cross the BBB and deliver pharmaceuticals to the brain for therapeutic treatment of neurological disorders. These disorders include Parkinson's disease, Alzheimer's disease, schizophrenia, depression, and brain tumors. Part of the difficulty in finding cures for these central nervous system (CNS) disorders is that there is yet no truly efficient delivery method for drugs to cross the BBB. Antibiotics, antineoplastic agents, and a variety of CNS-active drugs, especially neuropeptides, are a few examples of molecules that cannot pass the BBB alone. With the aid of nanoparticle delivery systems, however, studies have shown that some drugs can now cross the BBB, and even exhibit lower toxicity and decrease adverse effects throughout the body. Toxicity is an important concept for pharmacology because high toxicity levels in the body could be detrimental to the patient by affecting other organs and disrupting their function. Further, the BBB is not the only physiological barrier for drug delivery to the brain. Other biological factors influence how drugs are transported throughout the body and how they target specific locations for action. Some of these pathophysiological factors include blood flow alterations, edema and increased intracranial pressure, metabolic perturbations, and altered gene expression and protein synthesis. Though there exist many obstacles that make developing a robust delivery system difficult, nanoparticles provide a promising mechanism for drug transport to the CNS.

Nanoparticle drug delivery systems are engineered technologies that use nanoparticles for the targeted delivery and controlled release of therapeutic agents. The modern form of a drug delivery system should minimize side-effects and reduce both dosage and dosage frequency. Recently, nanoparticles have aroused attention due to their potential application for effective drug delivery.

Hamid Ghandehari is an Iranian-American drug delivery research scientist, and a professor in the Departments of Pharmaceutics and Pharmaceutical Chemistry and Biomedical Engineering at the University of Utah. His research is focused in recombinant polymers for drug and gene delivery, nanotoxicology of dendritic and inorganic constructs, water-soluble polymers for targeted delivery and poly(amidoamine) dendrimers for oral delivery.

A nasal vaccine is a vaccine administered through the nose that stimulates an immune response without an injection. It induces immunity through the inner surface of the nose, a surface that naturally comes in contact with many airborne microbes. Nasal vaccines are emerging as an alternative to injectable vaccines because they do not use needles and can be introduced through the mucosal route. Nasal vaccines can be delivered through nasal sprays to prevent respiratory infections, such as influenza.

<span class="mw-page-title-main">Mark Prausnitz</span> Chemical engineer

Mark Robert Prausnitz is an American chemical engineer, currently Regents’ Professor and J. Erskine Love, Jr. Chair in Chemical & Biomolecular Engineering at the Georgia Institute of Technology. He also serves as adjunct professor of biomedical engineering at Emory University and Adjunct Professor of Chemical & Biomolecular Engineering at the Korea Advanced Institute of Science and Technology. He is known for pioneering microneedle technology for minimally invasive drug and vaccine administration, which has found applications in transdermal, ocular, oral, and sustained release delivery systems.

Chitosan-poly is a composite that has been increasingly used to create chitosan-poly(acrylic acid) nanoparticles. More recently, various composite forms have come out with poly(acrylic acid) being synthesized with chitosan which is often used in a variety of drug delivery processes. Chitosan which already features strong biodegradability and biocompatibility nature can be merged with polyacrylic acid to create hybrid nanoparticles that allow for greater adhesion qualities as well as promote the biocompatibility and homeostasis nature of chitosan poly(acrylic acid) complex. The synthesis of this material is essential in various applications and can allow for the creation of nanoparticles to facilitate a variety of dispersal and release behaviors and its ability to encapsulate a multitude of various drugs and particles.

Protein nanotechnology is a burgeoning field of research that integrates the diverse physicochemical properties of proteins with nanoscale technology. This field assimilated into pharmaceutical research to give rise to a new classification of nanoparticles termed protein nanoparticles (PNPs). PNPs garnered significant interest due to their favorable pharmacokinetic properties such as high biocompatibility, biodegradability, and low toxicity Together, these characteristics have the potential to overcome the challenges encountered with synthetic NPs drug delivery strategies. These existing challenges including low bioavailability, a slow excretion rate, high toxicity, and a costly manufacturing process, will open the door to considerable therapeutic advancements within oncology, theranostics, and clinical translational research.

<span class="mw-page-title-main">Intracellular delivery</span> Scientific research area

Intracellular delivery is the process of introducing external materials into living cells. Materials that are delivered into cells include nucleic acids, proteins, peptides, impermeable small molecules, synthetic nanomaterials, organelles, and micron-scale tracers, devices and objects. Such molecules and materials can be used to investigate cellular behavior, engineer cell operations or correct a pathological function.

Intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly into the nervous system. Though pharmaceuticals can be injected into the nose, some concerns include injuries, infection, and safe disposal. Studies demonstrate improved patient compliance with inhalation. Treating brain diseases has been a challenge due to the blood brain barrier. Previous studies evaluated the efficacy of delivery therapeutics through intranasal route for brain diseases and mental health conditions. Intranasal administration is a potential route associated with high drug transfer from nose to brain and drug bioavailability.

<span class="mw-page-title-main">Invasomes</span> Transdermal drug delivery method

An invasome is a type of artificial vesicle nanocarrier that transport substances through the skin, the most superficial biological barrier. Vesicles are small particles surrounded by a lipid layer that can carry substances into and out of the cell. Artificial vesicles can be engineered to deliver drugs within the cell, with specific applications within transdermal drug delivery. However, the skin proves to be a barrier to effective penetration and delivery of drug therapies. Thus, invasomes are a new generation of vesicle with added structural components to assist with skin penetration.

Moein Moghimi is a British professor and researcher in the fields of nanomedicine, drug delivery and biomaterials. He is currently the professor of Pharmaceutics and Nanomedicine at the School of Pharmacy and the Translational and Clinical Research Institute at Newcastle University. He is also an adjoint professor at the Skaggs School of Pharmacy, University of Colorado Denver.

<span class="mw-page-title-main">Microneedles</span> Medical instruments

Microneedles (MNs) are medical tools used for microneedling, primarily in drug delivery, disease diagnosis, and collagen induction therapy. Known for their minimally invasive and precise nature, MNs consist of arrays of micro-sized needles ranging from 25μm to 2000μm. Although the concept of microneedling was first introduced in the 1970s, its popularity has surged due to its effectiveness in drug delivery and its cosmetic benefits.

References

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