Stretch-triggered drug delivery

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Stretch-triggered drug delivery is a method of controlled drug delivery stimulated by mechanical forces. The most commonly used materials for stretch-triggered autonomous drug release systems are hydrogels and elastomers. [1]

Contents

This method of drug delivery falls in the category of stimuli-responsive drug delivery systems which include pH, temperature, and redox-responsive systems. Mechanical forces occur naturally throughout the human body therefore, stretch-triggered drug delivery systems may be used to autonomously deliver medications to the body when needed. The use of autonomous drug release systems reduces outcomes such as delays in receiving treatment and inaccurate dosages. [1] Autonomous drug release systems induced by stretch apply to drugs such as antimicrobial agents, cardiovascular medication, and anticancer drugs. [1] Theranostic agents are also applicable to this drug delivery system, allowing for simultaneous treatment and diagnosis of diseases. [2]

Types of Mechanical Stimuli

Three main types of mechanical stimuli; compression force, tensile force, and shear force. Compression, Tensile and shear Force.png
Three main types of mechanical stimuli; compression force, tensile force, and shear force.

Compression, tension, and shear are the three main types of mechanical stimuli. [3] [4] Compression force is when an object experiences forces from two sides, going in opposite directions, causing it to become compacted. Tensile force is when an object experiences forces from two sides, pointing in opposite directions, causing it to stretch. Shear forces are when an object experiences forces that are parallel and are going in opposite directions. Ultrasound and magnetic fields are also examples of mechanical forces. [5] Depending on the mechanical stimuli, a different material may improve the desired results. [2] The human body is exposed to mechanical forces on or within bones, organs, joints, blood vessels, and cartilage. [1] [5]

Naturally Occurring Mechanical Stimuli

A drug release mechanism that is triggered by the stretching of the contact lens due to natural eye movements. WikiImage2.png
A drug release mechanism that is triggered by the stretching of the contact lens due to natural eye movements.

There are naturally occurring mechanical forces in the human body such as increased stress within blood vessels due to atherosclerotic plaque. [4] The naturally occurring mechanical forces in the body enable the self-administration of medications. [3] Motion-triggered drug delivery of anticancer therapy is achievable through the natural forces generated by organ movements. [7] Research has been conducted on contact lenses that are pre-loaded with glaucoma medication that is released by the stretch of the contact lens during natural eye movements. [6] The movement of joints has been used to trigger the release of antibacterial drugs into the body. [5]

Applications

Example of a drug release system triggered by the stretching of an elastomer as a consequence of a finger bending. WikiImage3.png
Example of a drug release system triggered by the stretching of an elastomer as a consequence of a finger bending.

Stretch-triggered drug delivery has a variety of applications. Intracellular transfection can be achieved through drug-delivery systems that are responsive to mechanical stimuli. [3] Drug release can be controlled by triggers due to forces experienced by the body from daily motions. [4] Mechanical triggers have been applied to polymers to release 2-furylcarbonil derivatives which then trigger the release of molecular cargo. [8] An application of stretch-triggered drug delivery systems is the delivery of chemotherapy triggered by esophageal stent expansion. [4] Also, the incorporation of several drugs into stretch-triggered autonomous drug release systems is a possibility, allowing drugs to be released by the same or different signals. [1] Stretch-triggered drug delivery is also applied to nanoparticle-loaded stretchable elastomers that release drugs due to their expanded surface area. [7] Stretch-triggered drug delivery has been applied to the cardiovascular system through the use of drug-loaded hydrogels that lead to increased vascularization. [5] A research study demonstrated that quinine-loaded hydrogels resulted in restricted growth of bacteria as a result of exposure to stretching. [9]

Limitations

Due to the limited research on mechanical force-responsive drug delivery systems, the effects of mechanical forces on cells remain unclear. [10] Current research on stretch-triggered drug delivery systems mostly involves in vitro studies, therefore, extensive in-vivo studies are required to further improve knowledge in this subject. [10] [4] A limitation of current technology is the release of drugs in the absence of tensile triggers and a limit of loading agents. [4] Transdermal drug delivery systems may include stretch-triggered technology but these devices are typically used for long-term administration, making drug reloading a topic of concern. [11] Issues of environmental impact are also a concern when it comes to transdermal drug delivery due to the material's lack of ability to biodegrade and associated electronic waste. [11] An area of interest regarding drug delivery devices that use naturally occurring triggers is the variability of physiological parameters between people. [11] This makes it difficult to set a standard of what will trigger this technology.

Related Research Articles

<span class="mw-page-title-main">Hydrogel</span> Soft water-rich polymer gel

A hydrogel is a biphasic material, a mixture of porous, permeable solids and at least 10% by weight or volume of interstitial fluid composed completely or mainly by water. In hydrogels the porous permeable solid is a water insoluble three dimensional network of natural or synthetic polymers and a fluid, having absorbed a large amount of water or biological fluids. These properties underpin several applications, especially in the biomedical area. Many hydrogels are synthetic, but some are derived from nature. The term 'hydrogel' was coined in 1894.

<span class="mw-page-title-main">Electroactive polymer</span>

An electroactive polymer (EAP) is a polymer that exhibits a change in size or shape when stimulated by an electric field. The most common applications of this type of material are in actuators and sensors. A typical characteristic property of an EAP is that they will undergo a large amount of deformation while sustaining large forces.

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.

Modified-release dosage is a mechanism that delivers a drug with a delay after its administration or for a prolonged period of time or to a specific target in the body.

Poly(N-isopropylacrylamide) (variously abbreviated PNIPA, PNIPAM, PNIPAAm, NIPA, PNIPAA or PNIPAm) is a temperature-responsive polymer that was first synthesized in the 1950s. It can be synthesized from N-isopropylacrylamide which is commercially available. It is synthesized via free-radical polymerization and is readily functionalized making it useful in a variety of applications.

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. 

Smart polymers, stimuli-responsive polymers or functional polymers are high-performance polymers that change according to the environment they are in.

Nanocomposite hydrogels are nanomaterial-filled, hydrated, polymeric networks that exhibit higher elasticity and strength relative to traditionally made hydrogels. A range of natural and synthetic polymers are used to design nanocomposite network. By controlling the interactions between nanoparticles and polymer chains, a range of physical, chemical, and biological properties can be engineered. The combination of organic (polymer) and inorganic (clay) structure gives these hydrogels improved physical, chemical, electrical, biological, and swelling/de-swelling properties that cannot be achieved by either material alone. Inspired by flexible biological tissues, researchers incorporate carbon-based, polymeric, ceramic and/or metallic nanomaterials to give these hydrogels superior characteristics like optical properties and stimulus-sensitivity which can potentially be very helpful to medical and mechanical fields.

Hydrogels are three-dimensional networks consisting of chemically or physically cross-linked hydrophilic polymers. The insoluble hydrophilic structures absorb polar wound exudates and allow oxygen diffusion at the wound bed to accelerate healing. Hydrogel dressings can be designed to prevent bacterial infection, retain moisture, promote optimum adhesion to tissues, and satisfy the basic requirements of biocompatibility. Hydrogel dressings can also be designed to respond to changes in the microenvironment at the wound bed. Hydrogel dressings should promote an appropriate microenvironment for angiogenesis, recruitment of fibroblasts, and cellular proliferation.

<span class="mw-page-title-main">Ophthalmic drug administration</span>

Ophthalmic drug administration is the administration of a drug to the eyes, most typically as an eye drop formulation. Topical formulations are used to combat a multitude of diseased states of the eye. These states may include bacterial infections, eye injury, glaucoma, and dry eye. However, there are many challenges associated with topical delivery of drugs to the cornea of the eye.

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">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.

<span class="mw-page-title-main">Gated drug delivery systems</span> Method of controlled drug release

Gated drug delivery systems are a method of controlled drug release that center around the use of physical molecules that cover the pores of drug carriers until triggered for removal by an external stimulus. Gated drug delivery systems are a recent innovation in the field of drug delivery and pose as a promising candidate for future drug delivery systems that are effective at targeting certain sites without having leakages or off target effects in normal tissues. This new technology has the potential to be used in a variety of tissues over a wide range of disease states and has the added benefit of protecting healthy tissues and reducing systemic side effects.

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.

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.

Bioprinting drug delivery is a method of using the three-dimensional printing of biomaterials through an additive manufacturing technique to develop drug delivery vehicles that are biocompatible tissue-specific hydrogels or implantable devices. 3D bioprinting uses printed cells and biological molecules to manufacture tissues, organs, or biological materials in a scaffold-free manner that mimics living human tissue to provide localized and tissue-specific drug delivery, allowing for targeted disease treatments with scalable and complex geometry.

Ultrasound-triggered drug delivery using stimuli-responsive hydrogels refers to the process of using ultrasound energy for inducing drug release from hydrogels that are sensitive to acoustic stimuli. This method of approach is one of many stimuli-responsive drug delivery-based systems that has gained traction in recent years due to its demonstration of localization and specificity of disease treatment. Although recent developments in this field highlight its potential in treating certain diseases such as COVID-19, there remain many major challenges that need to be addressed and overcome before more related biomedical applications are clinically translated into standard of care.

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.

References

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  8. ↑ Hu, Xiaoran; Zeng, Tian; Husic, Corey C.; Robb, Maxwell J. (2021). "Mechanically triggered release of functionally diverse molecular payloads from masked 2-furylcarbinol derivatives". ACS Central Science. 7 (7): 1216–1224. doi:10.1021/acscentsci.1c00460. PMC   8323246 . PMID   34345671.
  9. ↑ Ballance, William C.; Seo, Yongbeom; Baek, Kwanghyun; Chalifoux, Madeleine; Kim, Donghyun; Kong, Hyunjoon (2018). "Stretchable, anti-bacterial hydrogel activated by large mechanical deformation". Journal of Controlled Release. 275: 1–11. doi: 10.1016/j.jconrel.2018.02.009 . PMID   29427648. S2CID   4468800.
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