15.4 Bioengineering Approaches in Drug Discovery and Delivery
3 min read•july 25, 2024
Bioengineering is revolutionizing drug discovery and delivery. It's making the process faster, cheaper, and more personalized. From to , these techniques are finding new drugs and testing them more efficiently.
Targeted drug delivery is a game-changer. It gets drugs where they need to go, reducing side effects. and are making this possible, with things like liposomes and . These advances are making treatments more effective and easier for patients.
Drug Discovery Techniques
Role of bioengineering in drug discovery
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Top images from around the web for Role of bioengineering in drug discovery
Frontiers | Computational Approaches in Preclinical Studies on Drug Discovery and Development View original
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Frontiers | QSAR-Based Virtual Screening: Advances and Applications in Drug Discovery View original
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- Enhances efficiency in drug development process reducing time and cost of bringing new drugs to market while improving success rates of drug candidates (Moderna's COVID-19 vaccine)
- Enables personalized medicine approaches tailoring treatments to individual patient profiles (cancer immunotherapy)
- Facilitates development of novel drug delivery systems improving drug efficacy and patient compliance ()
- Integrates computational modeling and simulation predicting drug behavior and interactions in silico ()
- Utilizes tissue engineering for drug testing creating more accurate models for drug screening ()
Bioengineering techniques for drug screening
- High-throughput screening (HTS) automates testing of large compound libraries using robotics and data processing software to identify potential drug candidates rapidly (10,000+ compounds/day)
- Microfluidics utilizes miniaturized devices for drug testing allowing precise control of fluid flow and mixing enabling single-cell analysis and organ-on-a-chip models (lung-on-a-chip)
- Cell-based assays evaluate drug effects on living cells providing insights into cellular responses and toxicity (cytotoxicity assays)
- DNA-encoded libraries combine chemical synthesis with DNA tagging allowing screening of vast compound collections (billions of molecules)
- In silico screening uses computational methods to predict drug-target interactions employing machine learning and artificial intelligence algorithms ()
Drug Delivery Systems
Principles of targeted drug delivery
- Selective accumulation of drugs at target sites improves drug concentration at desired locations while minimizing exposure to healthy tissues ()
- Utilization of targeting mechanisms:
- Passive targeting exploits physiological differences between diseased and healthy tissues
- Active targeting uses specific ligands to bind to target cells or tissues
- of drugs maintains therapeutic drug levels over extended periods reducing frequency of drug administration (extended-release formulations)
- Enhanced permeability and retention (EPR) effect allows accumulation of nanoparticles in tumor tissues (liposomal doxorubicin)
- triggers drug release in response to specific environmental cues (pH-sensitive, temperature-sensitive, or enzyme-responsive systems)
Nanomedicine and biomaterials for drug delivery
- Nanoparticle-based drug carriers:
- Liposomes phospholipid vesicles for drug encapsulation (Doxil)
- biodegradable carriers for sustained release (PLGA nanoparticles)
- highly branched structures for drug loading (PAMAM dendrimers)
- Biomaterial-based drug delivery systems:
- Hydrogels 3D networks for controlled drug release (contact lenses for ocular drug delivery)
- long-term drug delivery platforms (drug-eluting stents)
- Surface modification of nanocarriers:
- increases circulation time and reduces immunogenicity (pegylated interferon)
- Antibody conjugation enhances targeting specificity ()
- combines diagnostic and therapeutic functions in a single platform (iron oxide nanoparticles for MRI and hyperthermia)
- Overcoming biological barriers:
- (transferrin-functionalized nanoparticles)
- (cell-penetrating peptides)
- Challenges and considerations:
- and (silk fibroin scaffolds)
- Scalability and manufacturing processes (microfluidic-based nanoparticle synthesis)
- Regulatory and safety concerns (FDA guidelines for nanomedicine)
Key Terms to Review (37)
3D Organoids: 3D organoids are miniaturized and simplified versions of organs that are grown in vitro from stem cells, mimicking the architecture and functionality of real tissues. These structures are significant in bioengineering as they provide a more accurate platform for studying human biology, disease modeling, and drug discovery, allowing researchers to test drugs on more representative biological systems than traditional 2D cell cultures.
3D printing of pharmaceuticals: 3D printing of pharmaceuticals refers to the innovative process of using additive manufacturing techniques to create customized drug formulations and delivery systems. This technology allows for the precise control of drug dosage, release profiles, and shapes, which can lead to improved therapeutic outcomes and personalized medicine. By leveraging bioengineering approaches, this method enhances drug discovery and delivery through tailored solutions that address individual patient needs.
Antibody-drug conjugates: Antibody-drug conjugates (ADCs) are targeted cancer therapies that combine an antibody with a cytotoxic drug. This innovative approach allows for the delivery of potent drugs directly to cancer cells, minimizing damage to healthy tissues while enhancing the therapeutic effect. By leveraging the specificity of antibodies for tumor-associated antigens, ADCs improve the efficacy and safety profiles of traditional chemotherapy.
Bioavailability: Bioavailability refers to the proportion of a drug or substance that enters the systemic circulation when introduced into the body and is available for therapeutic action. This concept is crucial because it helps determine how effectively a drug can achieve its intended effects, influencing drug-target interactions, the rational design of drugs, and strategies in drug delivery systems.
Biocompatibility: Biocompatibility refers to the ability of a material to perform its desired function in a specific biological environment without eliciting an adverse reaction. This concept is crucial in ensuring that medical devices and drug delivery systems interact safely with the body, promoting effective therapeutic outcomes while minimizing harmful side effects. Understanding biocompatibility helps in selecting materials that support healing, integration, and functionality in biomedical applications.
Biodegradability: Biodegradability is the ability of a substance to be broken down by living organisms, particularly by microorganisms like bacteria and fungi, into simpler, non-toxic substances. This process is essential in assessing the environmental impact of materials, especially in fields like drug discovery and delivery, where the development of biodegradable materials can lead to safer and more sustainable medical solutions.
Blood-brain barrier penetration: Blood-brain barrier penetration refers to the ability of substances, such as drugs, to cross the blood-brain barrier (BBB), a selective permeability barrier that protects the brain from harmful agents while allowing essential nutrients to pass through. This process is crucial in drug discovery and delivery since many therapeutic agents struggle to reach their target sites within the central nervous system due to the restrictive nature of the BBB, making it a significant challenge in treating neurological diseases.
Clinical trials: Clinical trials are systematic studies conducted to evaluate the safety and efficacy of new drugs or medical treatments in humans. These trials are essential in the drug discovery and delivery process, providing critical data that informs regulatory approval and clinical practice, ensuring that new therapies are both effective and safe for patient use.
Combination Therapy: Combination therapy refers to the use of two or more therapeutic agents simultaneously to enhance treatment effectiveness, reduce resistance, or mitigate side effects. This approach leverages the synergistic effects of different drugs to improve patient outcomes, particularly in diseases like cancer and HIV, where single-agent therapies may be insufficient.
Controlled Release: Controlled release refers to the method of delivering drugs in a way that prolongs their therapeutic effect by releasing them at a predetermined rate over a specific period. This approach enhances the drug's efficacy while minimizing side effects, making it an essential strategy in drug delivery systems. By using various bioengineering techniques, controlled release can improve patient compliance and optimize drug pharmacokinetics.
Dendrimers: Dendrimers are highly branched, tree-like macromolecules that have a well-defined structure and can be precisely engineered at the molecular level. Their unique architecture allows for a high degree of functionalization and surface customization, making them particularly valuable in various applications including drug delivery and molecular recognition in bioengineering. The ability to carry multiple drug molecules simultaneously and target specific cells enhances their potential in improving therapeutic outcomes.
Enhanced Permeability and Retention Effect: The enhanced permeability and retention (EPR) effect refers to the phenomenon where certain macromolecules and nanoparticles preferentially accumulate in tumor tissue due to the leaky vasculature and impaired lymphatic drainage typical of tumors. This effect is significant in drug delivery systems as it allows for targeted therapy, maximizing the concentration of therapeutic agents in cancerous tissues while minimizing exposure to healthy tissues.
FDA Approval: FDA approval is the authorization granted by the U.S. Food and Drug Administration (FDA) for a drug or medical device to be marketed and sold in the United States after it has been rigorously tested for safety and efficacy. This process is essential in ensuring that new therapies meet high standards before they can be made available to patients, reflecting a critical step in drug discovery and delivery approaches.
Half-life: Half-life is the time required for the concentration of a substance to reduce to half of its initial value. This concept is crucial in understanding reaction rates, where it helps describe how quickly reactants are converted to products, particularly in first-order reactions. Additionally, half-life is significant in drug design, as it influences dosing schedules and effectiveness, and plays a role in bioengineering approaches that enhance drug delivery and efficacy.
High-throughput screening: High-throughput screening (HTS) is a method that allows researchers to quickly conduct millions of chemical, genetic, or pharmacological tests to identify potential drug candidates or enzyme activities. This technique relies on automation and data analysis to efficiently evaluate vast libraries of compounds, facilitating the rapid discovery of new drugs and the understanding of biological processes.
Hydrogels: Hydrogels are three-dimensional polymeric networks that can retain large amounts of water while maintaining their structure. These materials are crucial in various applications due to their unique ability to swell and absorb fluids, making them particularly useful in drug delivery systems where controlled release of therapeutic agents is essential.
Implantable devices: Implantable devices are medical instruments that are surgically inserted into the body to enhance or replace biological functions. These devices can deliver drugs, monitor health conditions, or support physiological processes, playing a critical role in the advancements of personalized medicine and targeted therapies.
In silico modeling: In silico modeling refers to the use of computer simulations and computational techniques to study and predict biological and chemical processes. This approach allows researchers to analyze complex systems, optimize drug design, and evaluate potential therapeutic effects without relying solely on laboratory experiments. The power of in silico modeling lies in its ability to handle large datasets and simulate interactions at a molecular level, which is crucial for advancing drug discovery and delivery strategies.
Intracellular delivery of macromolecules: Intracellular delivery of macromolecules refers to the process by which large biomolecules, such as proteins, nucleic acids, and polysaccharides, are transported into living cells to exert therapeutic effects or to study cellular processes. This delivery is crucial in bioengineering approaches, as it allows for targeted treatment strategies in drug discovery and enhances the understanding of cellular functions through genetic manipulation or protein supplementation.
Liposome formulation: Liposome formulation refers to the process of creating liposomes, which are spherical vesicles made from lipid bilayers that encapsulate drugs or other therapeutic agents for targeted delivery in the body. This technique is crucial in bioengineering as it enhances the bioavailability and stability of drugs, allowing for controlled release and minimizing side effects during drug delivery.
Microencapsulation: Microencapsulation is a process that involves enclosing active substances within a protective coating, creating tiny capsules that can control the release of these substances over time. This technique is crucial in various applications, particularly in drug delivery, where it enhances the stability and bioavailability of drugs while minimizing side effects. Microencapsulation allows for targeted delivery and can improve the efficacy of therapeutic agents by ensuring they are released at the right location and time within the body.
Microfluidics: Microfluidics is the science and technology of manipulating and analyzing fluids at the microscale, typically involving channels with dimensions in the micrometer range. This technology is crucial for applications in drug discovery and delivery, as it allows for precise control of small fluid volumes, enabling rapid and efficient experiments that can improve the development of therapeutics and diagnostics.
Molecular docking: Molecular docking is a computational technique used to predict the preferred orientation of one molecule, typically a drug candidate, when it binds to a target protein. This process is vital in rational drug design, allowing scientists to visualize how potential drugs interact with biological targets at the molecular level. By assessing these interactions, researchers can optimize drug candidates for better efficacy and reduced side effects.
Monoclonal antibodies: Monoclonal antibodies are laboratory-produced molecules engineered to serve as substitutes for natural antibodies in the immune system. These antibodies are created by identical immune cells that are clones of a unique parent cell, allowing for highly specific targeting of antigens. Their precision makes them invaluable in drug discovery and delivery, particularly in treating diseases like cancer and autoimmune disorders.
Nanomedicine: Nanomedicine is a branch of medicine that uses nanotechnology to develop new diagnostic, therapeutic, and preventive techniques to improve healthcare. By manipulating materials at the nanoscale (1 to 100 nanometers), it enables more precise drug delivery, targeted therapies, and the creation of advanced medical devices. This innovative approach enhances the effectiveness of treatments and minimizes side effects, making it a vital aspect of modern bioengineering.
Nanoparticle delivery: Nanoparticle delivery refers to the use of engineered nanoparticles as carriers to transport drugs or therapeutic agents directly to targeted cells or tissues in the body. This approach improves the efficacy and safety of treatments by enhancing drug solubility, controlling release rates, and minimizing side effects, thereby playing a vital role in modern drug discovery and delivery techniques.
Nanotheranostics: Nanotheranostics refers to the combined approach of nanotechnology in the fields of therapeutics and diagnostics, enabling simultaneous drug delivery and imaging at the nanoscale. This innovative strategy allows for targeted treatment and real-time monitoring of diseases, particularly in cancer, by utilizing nanoparticles that can carry therapeutic agents while also providing diagnostic information. The integration of these functions enhances personalized medicine by improving treatment efficacy and reducing side effects.
Pegylation: Pegylation is the process of attaching polyethylene glycol (PEG) molecules to a drug, protein, or other therapeutic agents to improve their properties. This modification can enhance the solubility, stability, and bioavailability of the therapeutic compound, while also reducing immunogenicity and clearance rates in the body. As a result, pegylation is a widely used strategy in bioengineering approaches for drug discovery and delivery.
Polymeric nanoparticles: Polymeric nanoparticles are tiny particles made from polymers, typically ranging from 1 to 1000 nanometers in size, used for drug delivery, imaging, and other biomedical applications. These nanoparticles can encapsulate drugs, providing controlled release and targeted delivery, thus enhancing therapeutic efficacy while minimizing side effects. Their unique size and surface properties enable them to interact favorably with biological systems, making them a powerful tool in drug discovery and delivery.
Recombinant proteins: Recombinant proteins are proteins that are artificially produced through the combination of DNA from different sources, typically using techniques like recombinant DNA technology. This process allows for the expression of proteins that may not be naturally occurring in a specific organism or may require large quantities for research or therapeutic applications. By inserting the gene encoding a desired protein into a host organism, such as bacteria, yeast, or mammalian cells, scientists can produce these proteins for various uses, including drug development and therapeutic interventions.
Smart biomaterials: Smart biomaterials are advanced materials designed to interact dynamically with biological systems, adapting their properties in response to environmental stimuli. These materials play a crucial role in enhancing drug discovery and delivery by offering targeted therapeutic effects, controlled release mechanisms, and improved biocompatibility. By responding to specific triggers like pH, temperature, or biochemical signals, smart biomaterials optimize the efficacy of drugs while minimizing side effects.
Stimuli-responsive drug delivery: Stimuli-responsive drug delivery refers to a sophisticated approach in which drug release is controlled by external stimuli such as pH, temperature, light, or specific biological signals. This method enhances the therapeutic efficacy of drugs by ensuring that they are released in response to particular conditions, allowing for targeted and controlled treatment. By utilizing the unique characteristics of biological environments or external triggers, stimuli-responsive systems improve the specificity and reduce side effects associated with conventional drug delivery methods.
Targeted therapy: Targeted therapy is a type of cancer treatment that uses drugs or other substances to precisely identify and attack cancer cells while causing minimal harm to normal cells. This approach is based on the understanding of cancer's genetic, molecular, and cellular characteristics, which enables the development of therapies that specifically target those unique features. By focusing on specific pathways or mutations involved in tumor growth, targeted therapies aim to improve treatment outcomes and reduce side effects compared to traditional chemotherapy.
Therapeutic index: The therapeutic index is a measure of the safety and effectiveness of a drug, defined as the ratio of the dose that produces toxicity to the dose that produces the desired therapeutic effect. A higher therapeutic index indicates a wider margin of safety, meaning there is a larger difference between effective and harmful doses. Understanding the therapeutic index is crucial for determining appropriate dosages and minimizing adverse effects when developing and delivering medications.
Transdermal patches: Transdermal patches are drug delivery systems designed to deliver medication through the skin for systemic effects. They allow for controlled, sustained release of drugs over time, offering an alternative to oral or injectable routes of administration. This method enhances patient compliance and can provide a steady therapeutic effect while minimizing side effects and peak drug concentrations.
Tumor-targeted nanoparticles: Tumor-targeted nanoparticles are engineered drug delivery systems designed to specifically accumulate in tumor tissues while minimizing exposure to healthy tissues. These particles can be loaded with therapeutic agents and utilize various targeting mechanisms, such as surface modifications or ligands, to enhance their selectivity for cancer cells. This approach improves the efficacy of treatments and reduces side effects associated with conventional drug delivery methods.
Virtual screening: Virtual screening is a computational technique used to identify potential drug candidates from large libraries of compounds by predicting their interactions with biological targets. This method leverages algorithms and molecular modeling to efficiently evaluate and prioritize compounds based on their binding affinity, making it a crucial step in the drug discovery process. It allows researchers to reduce the number of compounds that need to be physically tested, ultimately accelerating the development of new therapies.