Nanocarrier

Last updated
Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range with various targeting ligands attached to their surface allowing for their surface-attachment and accumulation in pathological areas for treatment of disease. Liposome.jpg
Liposomes are composite structures made of phospholipids and may contain small amounts of other molecules. Though liposomes can vary in size from low micrometer range to tens of micrometers, unilamellar liposomes, as pictured here, are typically in the lower size range with various targeting ligands attached to their surface allowing for their surface-attachment and accumulation in pathological areas for treatment of disease.
Drug-loaded polymeric micelle formed from self-assembly of amphiphilic block copolymers in aqueous media. Micelle formation and drug encapsulation.svg
Drug-loaded polymeric micelle formed from self-assembly of amphiphilic block copolymers in aqueous media.
Drug-loaded polymeric micelles with various targeting functions. (A) Antibody-targeted micelles (B) ligand-targeted micelles (C) Micelles with cell-pentrating function. Drug-loaded polymeric micelles with various targeting functions.svg
Drug-loaded polymeric micelles with various targeting functions. (A) Antibody-targeted micelles (B) ligand-targeted micelles (C) Micelles with cell-pentrating function.

A nanocarrier is nanomaterial being used as a transport module for another substance, such as a drug. Commonly used nanocarriers include micelles, polymers, carbon-based materials, liposomes and other substances. [2] Nanocarriers are currently being studied for their use in drug delivery and their unique characteristics demonstrate potential use in chemotherapy. This class of materials was first reported by a team of researchers of University of Évora, Alentejo in early 1960's, and grew exponentially in relevance since then. [2]

Contents

Characterization

Nanocarriers range from sizes of diameter 1–1000 nm, [3] [4] however due to the width of microcapillaries being 200 nm, nanomedicine often refers to devices <200 nm. [4] Because of their small size, nanocarriers can deliver drugs to otherwise inaccessible sites around the body. Since nanocarriers are so small, it is oftentimes difficult to provide large drug doses using them. The emulsion techniques used to make nanocarriers also often result in low drug loading and drug encapsulation, providing a difficulty for the clinical use. [2]

Types

Nanocarriers discovered include polymer conjugates, polymeric nanoparticles, lipid-based carriers, dendrimers, carbon nanotubes, and gold nanoparticles. Lipid-based carriers include both liposomes and micelles. Examples of gold nanoparticles are gold nanoshells and nanocages. [3] Different types of nanomaterial being used in nanocarriers allows for hydrophobic and hydrophilic drugs to be delivered throughout the body. [5] Since the human body contains mostly water, the ability to deliver hydrophobic drugs effectively in humans is a major therapeutic benefit of nanocarriers. [6] Micelles are able to contain either hydrophilic or hydrophobic drugs depending on the orientation of the phospholipid molecules. [7] [8] Some nanocarriers contain nanotube arrays allowing them to contain both hydrophobic and hydrophilic drugs. [9]

One potential problem with nanocarriers is unwanted toxicity from the type of nanomaterial being used. Inorganic nanomaterial can also be toxic to the human body if it accumulates in certain cell organelles. [10] New research is being conducted to invent more effective, safer nanocarriers. Protein based nanocarriers show promise for use therapeutically since they occur naturally, and generally demonstrate less cytotoxicity than synthetic molecules. [11]

Targeted drug delivery

Nanocarriers are useful in the drug delivery process because they can deliver drugs to site-specific targets, allowing drugs to be delivered in certain organs or cells but not in others. Site-specificity is a major therapeutic benefit as it prevents drugs from being delivered to the wrong places. [5] [7] [8] [9] Nanocarriers show promise for use in chemotherapy because they can help decrease the adverse, broader-scale toxicity of chemotherapy on healthy, fast growing cells around the body. Since chemotherapy drugs can be extremely toxic to human cells, it is important that they are delivered to the tumor without being released into other parts of the body. [2] [5] [7] [8] Four methods in which nanocarriers can deliver drugs include passive targeting, active targeting, pH specificity, and temperature specificity.

Passive targeting

Enhanced permeability and retention (EPR) effect and passive targeting. Nanocarriers can extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage. Enhanced permeability and retention (EPR) effect and passive targeting.svg
Enhanced permeability and retention (EPR) effect and passive targeting. Nanocarriers can extravasate into the tumors through the gaps between endothelial cells and accumulate there due to poor lymphatic drainage.

Passive targeting refers to a nanocarrier's ability to travel down a tumor's vascular system, become trapped, and accumulate in the tumor. This accumulation is caused by the enhanced permeability and retention effect [2] [8] [12] which refers to the poly(ethylene oxide) (PEO) coating on the outside of many nanocarriers. PEO allows nanocarriers to travel through the leaky vasculature of a tumor, where they are unable to escape. The leaky vasculature of a tumor is the network of blood vessels that form in a tumor, which contain many small pores. These pores allow nanocarriers in, but also contain many bends that allow the nanocarriers to become trapped. As more nanocarriers become trapped, the drug accumulates at the tumor site. [12] This accumulation causes large doses of the drug to be delivered directly to the tumor site. [2] PEO may also have some adverse effects on cell-nanocarrier interactions, weakening the effects of the drug, since many nanocarriers must be incorporated into the cells before the drugs can be released. [12]

Active targeting

Active targeting involves the incorporation of targeting modules such as ligands or antibodies on the surface of nanocarriers that are specific to certain types of cells around the body. Nanocarriers have such a high surface-area to volume ratio allowing for multiple ligands to be incorporated on their surfaces. [3] These targeting modules allow for the nanocarriers to be incorporated directly inside of cells, but also have some drawbacks. Ligands may cause nanocarriers to become slightly more toxic due to non-specific binding, and positive charges on ligands may decrease drug delivery efficiency once inside of cells. [8] [12] Active targeting has been shown to help overcome multi-drug resistance in tumor cells. [13]

pH specificity

Certain nanocarriers will only release the drugs they contain in specific pH ranges. pH specificity also allows nanocarriers to deliver drugs directly to a tumor site. [2] [7] Tumors are generally more acidic than normal human cells, with a pH around 6.8. Normal tissue has a pH of around 7.4. [2] Nanocarriers that only release drugs at certain pH ranges can therefore be used to release the drug only within acidic tumor environments. [2] [7] [12] High acidic environments cause the drug to be released due to the acidic environment degrading the structure of the nanocarrier. [14] These nanocarriers will not release drugs in neutral or basic environments, effectively targeting the acidic environments of tumors while leaving normal body cells untouched. [2] [12] This pH sensitivity can also be induced in micelle systems by adding copolymer chains to micelles that have been determined to act in a pH independent manor. [8] These micelle-polymer complexes also help to prevent cancer cells from developing multi-drug resistance. The low pH environment triggers a quick release of the micelle polymers, causing a majority of the drug to be released at once, rather than gradually like other drug treatments. This quick release mechanism significantly decreases the time it takes for anticancer drugs to kill a tumor, effectively preventing the tumor from having time to undergo mutations that would render it drug resistant. [8]

Temperature specificity

Some nanocarriers have also been shown to deliver drugs more effectively at certain temperatures. Since tumor temperatures are generally higher than temperatures throughout the rest of the body, around 40 °C, this temperature gradient helps act as safeguard for tumor-specific site delivery. [7]

Uses

Most of research on nanocarriers is being applied to their potential use in drug delivery, especially in chemotherapy. [15] Since nanocarriers can be used to specifically target the small pores, lower pH's, and higher temperatures of tumors, they have the potential to lower the toxicity of many chemotherapy drugs. [2] [5] [7] [8] Also, since almost 75% of anticancer drugs are hydrophobic, and therefore demonstrate difficulty in delivery inside human cells, the use of micelles to stabilize, and effectively mask the hydrophobic nature of hydrophobic drugs provides new possibilities for hydrophobic anticancer drugs. [6]

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">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.

Targeted drug delivery, sometimes called smart drug delivery, is a method of delivering medication to a patient in a manner that increases the concentration of the medication in some parts of the body relative to others. This means of delivery is largely founded on nanomedicine, which plans to employ nanoparticle-mediated drug delivery in order to combat the downfalls of conventional drug delivery. These nanoparticles would be loaded with drugs and targeted to specific parts of the body where there is solely diseased tissue, thereby avoiding interaction with healthy tissue. The goal of a targeted drug delivery system is to prolong, localize, target and have a protected drug interaction with the diseased tissue. The conventional drug delivery system is the absorption of the drug across a biological membrane, whereas the targeted release system releases the drug in a dosage form. The advantages to the targeted release system is the reduction in the frequency of the dosages taken by the patient, having a more uniform effect of the drug, reduction of drug side-effects, and reduced fluctuation in circulating drug levels. The disadvantage of the system is high cost, which makes productivity more difficult, and the reduced ability to adjust the dosages.

A nanogel is a polymer-based, crosslinked hydrogel particle on the sub-micron scale. These complex networks of polymers present a unique opportunity in the field of drug delivery at the intersection of nanoparticles and hydrogel synthesis. Nanogels can be natural, synthetic, or a combination of the two and have a high degree of tunability in terms of their size, shape, surface functionalization, and degradation mechanisms. Given these inherent characteristics in addition to their biocompatibility and capacity to encapsulate small drugs and molecules, nanogels are a promising strategy to treat disease and dysfunction by serving as delivery vehicles capable of navigating across challenging physiological barriers within the body. 

<span class="mw-page-title-main">Peptide amphiphile</span>

Peptide amphiphiles (PAs) are peptide-based molecules that self-assemble into supramolecular nanostructures including; spherical micelles, twisted ribbons, and high-aspect-ratio nanofibers. A peptide amphiphile typically comprises a hydrophilic peptide sequence attached to a lipid tail, i.e. a hydrophobic alkyl chain with 10 to 16 carbons. Therefore, they can be considered a type of lipopeptide. A special type of PA, is constituted by alternating charged and neutral residues, in a repeated pattern, such as RADA16-I. The PAs were developed in the 1990s and the early 2000s and could be used in various medical areas including: nanocarriers, nanodrugs, and imaging agents. However, perhaps their main potential is in regenerative medicine to culture and deliver cells and growth factors.

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.

Cancer treatments may vary depending on what type of cancer is being targeted, but one challenge remains in all of them: it is incredibly difficult to target without killing good cells. Cancer drugs and therapies all have very low selective toxicity. However, with the help of nanotechnology and RNA silencing, new and better treatments may be on the horizon for certain forms of cancer.

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.

<span class="mw-page-title-main">Polymer-protein hybrid</span> Nanostructures of protein-polymer conjugates

Polymer-protein hybrids are a class of nanostructure composed of protein-polymer conjugates. The protein component generally gives the advantages of biocompatibility and biodegradability, as many proteins are produced naturally by the body and are therefore well tolerated and metabolized. Although proteins are used as targeted therapy drugs, the main limitations—the lack of stability and insufficient circulation times still remain. Therefore, protein-polymer conjugates have been investigated to further enhance pharmacologic behavior and stability. By adjusting the chemical structure of the protein-polymer conjugates, polymer-protein particles with unique structures and functions, such as stimulus responsiveness, enrichment in specific tissue types, and enzyme activity, can be synthesized. Polymer-protein particles have been the focus of much research recently because they possess potential uses including bioseparations, imaging, biosensing, gene and drug delivery.

A protein corona is a dynamic coating of biomolecules, usually proteins, around the surface of a nanoparticle that forms spontaneously in colloidal nanomaterials upon exposure to biological mediums. Protein coronas can form in many different patterns depending on their size, shape, composition, charge, and surface functional groups, and have properties that vary in different environmental factors like temperature, pH, shearing stress, immersed media composition, and exposing time. These coatings are also changeable according to the conditions of the biochemical and physiochemical surface interactions. Types of protein coronas are known to be divided into two categories: “hard” and “soft”. “Hard” coronas have higher-affinity proteins that are irreversibly bonded to the nanoparticle surface, while “soft” coronas have lower-affinity proteins on the nanoparticle surface that are reversibly bound. These reversibly-bound proteins allow for the biomolecules in “soft” protein coronas to be exchanged or detached over time for various applications. This process is governed by the intermolecular protein-nanoparticle and protein-protein interactions that exist within a solution. In "soft" protein coronas, it is common to observe an exchange of proteins at the surface; larger proteins with lower affinities will often aggregate to the surface of the nanoparticle first, and over time, smaller proteins with higher affinities will replace them, "hardening" the corona, known as the Vroman effect.

Cytokines are polypeptides or glycoproteins that help immune cells communicate to each other to induce proliferation, activation, differentiation, and inflammatory or anti-inflammatory signals in various cell types. Studies utilizing cytokines for antitumor therapies has increased significantly since 2000, and different cytokines provide unique antitumor activities. Cytokines hinder tumor cell development mostly through antiproliferative or proapoptotic pathways but can also interrupt development indirectly by eliciting immune cells to have cytotoxic effects against tumor cells. Even though there are FDA-approved cytokine therapies, there are two main challenges associated with cytokine delivery. The first is that cytokines have a short half-life, so frequent administration of high doses is required for therapeutic effect. The second is that systemic toxicity could occur if the cytokines delivered cause an intense immune response, known as a cytokine storm.

<span class="mw-page-title-main">Dextran drug delivery systems</span> Polymeric drug carrier

Dextran drug delivery systems involve the use of the natural glucose polymer dextran in applications as a prodrug, nanoparticle, microsphere, micelle, and hydrogel drug carrier in the field of targeted and controlled drug delivery. According to several in vitro and animal research studies, dextran carriers reduce off-site toxicity and improve local drug concentration at the target tissue site. This technology has significant implications as a potential strategy for delivering therapeutics to treat cancer, cardiovascular diseases, pulmonary diseases, bone diseases, liver diseases, colonic diseases, infections, and HIV.

Conventional drug delivery is limited by the inability to control dosing, target specific sites, and achieve targeted permeability. Traditional methods of delivering therapeutics to the body experience challenges in achieving and maintaining maximum therapeutic effect while avoiding the effects of drug toxicity. Many drugs that are delivered orally or parenterally do not include mechanisms for sustained release, and as a result they require higher and more frequent dosing to achieve any therapeutic effect for the patient. As a result, the field of drug delivery systems developed into a large focus area for pharmaceutical research to address these limitations and improve quality of care for patients. Within the broad field of drug delivery, the development of stimuli-responsive drug delivery systems has created the ability to tune drug delivery systems to achieve more controlled dosing and targeted specificity based on material response to exogenous and endogenous stimuli.

Pullulan bioconjugates are systems that use pullulan as a scaffold to attach biological materials to, such as drugs. These systems can be used to enhance the delivery of drugs to specific environments or the mechanism of delivery. These systems can be used in order to deliver drugs in response to stimuli, create a more controlled and sustained release, and provide a more targeted delivery of certain drugs.

<span class="mw-page-title-main">Reduction-sensitive nanoparticles</span> Drug delivery method

Reduction-sensitive nanoparticles (RSNP) consist of nanocarriers that are chemically responsive to reduction. Drug delivery systems using RSNP can be loaded with different drugs that are designed to be released within a concentrated reducing environment, such as the tumor-targeted microenvironment. Reduction-Sensitive Nanoparticles provide an efficient method of targeted drug delivery for the improved controlled release of medication within localized areas of the body.

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.

pH-responsive tumor-targeted drug delivery is a specialized form of targeted drug delivery that utilizes nanoparticles to deliver therapeutic drugs directly to cancerous tumor tissue while minimizing its interaction with healthy tissue. Scientists have used drug delivery as a way to modify the pharmacokinetics and targeted action of a drug by combining it with various excipients, drug carriers, and medical devices. These drug delivery systems have been created to react to the pH environment of diseased or cancerous tissues, triggering structural and chemical changes within the drug delivery system. This form of targeted drug delivery is to localize drug delivery, prolongs the drug's effect, and protect the drug from being broken down or eliminated by the body before it reaches the tumor.

<span class="mw-page-title-main">Ligand-targeted liposome</span> Ligand-targeted liposomes for use in medical applications

A ligand-targeted liposome (LTL) is a nanocarrier with specific ligands attached to its surface to enhance localization for targeted drug delivery. The targeting ability of LTLs enhances cellular localization and uptake of these liposomes for therapeutic or diagnostic purposes. LTLs have the potential to enhance drug delivery by decreasing peripheral systemic toxicity, increasing in vivo drug stability, enhancing cellular uptake, and increasing efficiency for chemotherapeutics and other applications. Liposomes are beneficial in therapeutic manufacturing because of low batch-to-batch variability, easy synthesis, favorable scalability, and strong biocompatibility. Ligand-targeting technology enhances liposomes by adding targeting properties for directed drug delivery.

Nanomaterials have gained significant attention in the field of cancer research and treatment due to their unique properties and potential applications. These materials, typically on the nanoscale, offer several advantages in the fight against cancer.

References

  1. ↑ Torchilin, V (2006). "Multifunctional nanocarriers". Advanced Drug Delivery Reviews. 58 (14): 1532–55. doi:10.1016/j.addr.2006.09.009. PMID   17092599.
  2. 1 2 3 4 5 6 7 8 9 10 11 Qian W, Sun D, Zhu R, Du X, Liu H, Wang S. pH-sensitive strontium carbonate nanoparticles as new anticancer vehicles for controlled etoposide release. International Journal of Nanomedicine. 2012;7:5781-5792.
  3. 1 2 3 Peer1 D, Kar J, Hong S, Farokhzad O, Margalit, Langer R. Nanocarriers as an emerging platform for cancer therapy. Nature. 2007; 2: 751-760.
  4. 1 2 Singh R, Lillard Jr JW (2009). "Nanoparticle-based targeted drug delivery". Experimental and Molecular Pathology. 86 (3): 215–223. doi:10.1016/j.yexmp.2008.12.004. PMC   3249419 . PMID   19186176.
  5. 1 2 3 4 Yu M, Zhao J, Feng S (2012). "Vitamin E TPGS prodrug micelles for hydrophilic drug delivery with neuroprotective effects". International Journal of Pharmaceutics. 438 (1–2): 98–106. doi:10.1016/j.ijpharm.2012.08.038. PMID   22954445.
  6. 1 2 Chena Y, Lob C, Linc Y, Hsiuea G (2013). "Rapamycin encapsulated in dual-responsive micelles for cancer therapy". Biomaterials. 34 (4): 1115–1127. doi:10.1016/j.biomaterials.2012.10.034. PMID   23146436.
  7. 1 2 3 4 5 6 7 Rezaei S, Nabid M, Niknejad H, Entezami A. Multifunctional and thermoresponsive unimolecular micelles for tumor-targeted delivery and site-specifically release of anticancer drugs. Polymer. 2012;53(16):3485-3497.
  8. 1 2 3 4 5 6 7 8 Wu H, Zhua L, Torchilin V (2013). "pH-sensitive poly(histidine)-PEG/DSPE-PEG co-polymer micelles for cytosolic drug delivery". Biomaterials. 34 (4): 1213–1222. doi:10.1016/j.biomaterials.2012.08.072. PMC   3587181 . PMID   23102622.
  9. 1 2 Moom A, Jonas A, Losic D. A multi-drug delivery system with sequential release using titania nanotube arrays. ChemComm. 2012;48:3348-3350.
  10. ↑ Wang J, Fang X, Liang W (2012). "Pegylated phospholipid micelles induce endoplasmic reticulum-dependent apoptosis of cancer cells but not normal cells". ACS Nano. 6 (6): 5018–5030. doi:10.1021/nn300571c. PMID   22578158.
  11. ↑ Elzoghby A, Samy W, Elgindy N (2012). "Protein-based nanocarriers as promising drug and gene delivery systems". Journal of Controlled Release. 161 (1): 38–49. doi:10.1016/j.jconrel.2012.04.036. PMID   22564368.
  12. 1 2 3 4 5 6 Cajota S, Van Butselea S, Paillardb A, Passiranib C, Garcionb E, Benoitb J, Varshneyc S, Jérômea C. Smart nanocarriers for pH-triggered targeting and release of hydrophobic drugs. Acta Biomaterialia. 2012;8(12):4215–4223.
  13. ↑ Sarisozen C, Vural I, Levchenko T, Hincal A, Torchilin V. PEG-PE-based micelles co-loaded with paclitaxel and cyclosporine A or loaded with paclitaxel and targeted by anticancer antibody overcome drug resistance in cancer cells. Drug Delivery. 2012;19(4):169-176.
  14. ↑ Viricel W, Mbarek A, Leblond J (2015). "Switchable Lipids: Conformational Change for Fast pH-Triggered Cytoplasmic Delivery" (PDF). Angewandte Chemie International Edition. 54 (43): 12743–12747. doi:10.1002/anie.201504661. PMID   26189870.
  15. ↑ Taléns-Visconti R, Díez-Sales O, de Julián-Ortiz JV, Nácher A (Apr 2022). "Nanoliposomes in Cancer Therapy: Marketed Products and Current Clinical Trials". International Journal of Molecular Sciences. 23 (8): 4249. PMID   35457065.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.