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[[File:Action photo of nasal spray on a black background.jpg|thumb|A [[nasal spray]] bottle being demonstrated.]]
Drug delivery involves various methods and technologies designed to transport pharmaceutical compounds to their target sites helping therapeutic effect. It involves principles related to drug preparation, route of administration, site-specific targeting, metabolism, and toxicity all aimed to optimize efficacy and safety, while improving patient convenience and compliance. A key goal of drug delivery is to modify a drug's pharmacokinetics and specificity by combining it with different , , and designed to control its distribution and activity in the body.Drug delivery is closely linked with dosage form and route of administration, the latter of which is sometimes considered to be part of the definition. Although the terms are often used interchangeably, they represent distinct concepts. The route of administration refers specifically to the path by which a drug enters the body, such as oral, parenteral, or transdermal. In contrast, the dosage form refers to the physical form in which the drug is manufactured and delivered, such as tablets, capsules, patches, inhalers or injectable solutions. These are various dosage forms and technologies which include but not limited to nanoparticles, Liposome, microneedles, and Hydrogel that can be used to enhance therapeutic efficacy and safety. The same route can accommodate multiple dosage forms; for example, the oral route may involve tablet, capsule, or liquid suspension. While the transdermal route may use a patch, gel, or cream. Drug delivery incorporates both of these concepts while encompassing a broader scope, including the design and engineering of systems that operate within or across these routes. Common routes of administration include oral, parenteral (injected), sublingual, topical, transdermal, nasal, ocular, rectal, and vaginal. However, modern drug delivery continue to expand the possibilities of these routes through novel and hybrid approaches.
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. 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. 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. Other factors that have potentially influenced the increase in drug delivery system development may include the increasing prevalence of both chronic and Infection diseases, as well as a general increased understanding of the pharmacology, pharmacokinetics, and pharmacodynamics of many drugs.
The concept of controlled-release medication dates back to the 1950s, when Dexedrine became the first such formulation on the market. This era saw the introduction of transdermal patches, which deliver drugs slowly through the skin. As technology progressed, new formulations were developed to match the specific properties of different drugs. Examples include long-acting depot injections for medication like Antipsychotic and hormone therapies, which remain effective for weeks or even months after a single dose.
Since the late 1990s, research has increasingly turned to nanotechnology asa way to improve controlled-released drug delivery. Nanoparticles, tiny carriers engineered at a molecular level, can protect drugs from being broken down too quickly in the body, improve how well they're absorbed, and deliver them directly to the tissues where they're needed. This targeted delivery not only reduces side effects but also helps patients stay on track with their treatments. These advances in nanotechnology are transforming the landscape of drug delivery and are emphasizing the importance of developing the next generation of CR systems.
Recent studies have shown the effectiveness of smart nanoparticles that respond to biological cues, such as pH or redox conditions, thereby delivering drugs more precisely to tumor sites. For instance, pH-sensitive nanoparticles take advantage of the lower pH in tumor cells to release the drugs, which boost effectiveness while protecting healthy cells. Additionally, the use of biocompatible materials and switching the nanoparticle surfaces have improved their accuracy and release of delivery systems.
Advances in design have also made it possible to create multi-functional nanoparticles that are capable of handling tough challenges like multi-drug resistance in cancer. These systems can carry more than one type of drug, targeting specific molecules, which helps to deliver a stronger punch to tumor tissues. Altogether, these breakthroughs point to a potential for nanoparticle-based controlled-release therapies in the fields of cancer therapy and personalized medicine.
Among the macromolecules studied, RNA delivery has made progress, especially with the success of RNA-based COVID-19 vaccines. While protein and DNA delivery have shown progress, proteins in live animals and DNA in lab settings, delivering these large molecules, still remain a complex task. Although oral administration is generally preferred by patients for convenience, it's rarely effective for biologics due to poor absorption. That being said, innovative technologies such as enzyme inhibitors, permeation enhancers, lipid-based nanoparticles, and microneedles are being used to improve oral bioavailability for these drugs.
One of the recent developments that has been successful is the use of lipid nanoparticles (LNPs) to deliver messenger RNA (mRNA). LNPs protect fragile mRNA from degradation and escape from endosomes so it can reach the cytoplasm and produce proteins. This delivery method gained worldwide recognition during COVID-19 pandemic with the approval of mRNA vaccines from Pfizer-BioTech and Moderna. The rapid rollout of these vaccines proved that LNPs are not only effective but also scalable for mass production and global use.
Looking beyond vaccines, mRNA therapies are now being explored for a range of therapeutic applications including cancer immunotherapy, genetic disorders, and other infectious diseases. Researchers are also testing alternative delivery systems, like exosomes and new types of nanoparticles, to make mRNA therapies safer and more efficient. However, challenges remain, as mRNA is highly sensitive to environmental conditions. To address this, ongoing research is expanding into new administration routes including inhalable or oral mNRA formulations. This could reduce production costs and make these therapies more accessible to the world.
To address this, researchers have turned to nanoparticles, tiny engineered carriers designed to sneak past the BBB and deliver drugs directly to the brain tissue These particles can be tailored to take advantage of the body's own transport systems. For example, by attaching certain molecules to their surfaces, nanoparticles can trigger receptor-mediated transcytosis, a natural process that allows them to pass through cells lining the BBB and enter the brain.This kind of targeted delivery helps reduce the drug's exposure to the rest of the body, lowering the risk of side effects and increasing concentration where it matters most. So far, this strategy has shown promise in delivering treatments to the brain for conditions like Alzheimer's and Parkinson's disease.
Several types of nanoparticles are being studied for this purpose. Liposomes, for instance, are small vesicles that can carry drugs and be modified to circulate longer or hone in on specific brain regions. Dendrimers, with their tree-like structure, can hold multiple drug molecules and targeting agents at once. Polymeric nanoparticles, made from biodegradable materials like polylactic acid (PLA) or polylactic-co-glycolic acid (PLGA), can be engineered to released drugs over time in a controlled way. Solid lipid nanoparticles offer another alternative, combining biocompatibility with the ability to cross barriers more efficiently. Altogether, these advances are paving the way for more effective and precise treatments for a range of neurological disorders.
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