15.4 Bioengineering Approaches in Drug Discovery and Delivery

Bioengineering is revolutionizing drug discovery and delivery. It's making the process faster, cheaper, and more personalized. From high-throughput screening to microfluidics, 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. Nanomedicine and smart biomaterials are making this possible, with things like liposomes and hydrogels. These advances are making treatments more effective and easier for patients.

Drug Discovery Techniques

Role of bioengineering in drug discovery

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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 (transdermal patches)
• Integrates computational modeling and simulation predicting drug behavior and interactions in silico (molecular docking)
• Utilizes tissue engineering for drug testing creating more accurate models for drug screening (3D organoids)

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 (virtual screening)

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 (tumor-targeted nanoparticles)
• Utilization of targeting mechanisms:
  1. Passive targeting exploits physiological differences between diseased and healthy tissues
  2. Active targeting uses specific ligands to bind to target cells or tissues
• Controlled release 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)
• Stimuli-responsive drug delivery 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)
  • Polymeric nanoparticles biodegradable carriers for sustained release (PLGA nanoparticles)
  • Dendrimers 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)
  • Implantable devices long-term drug delivery platforms (drug-eluting stents)
• Surface modification of nanocarriers:
  • PEGylation increases circulation time and reduces immunogenicity (pegylated interferon)
  • Antibody conjugation enhances targeting specificity (antibody-drug conjugates)
• Nanotheranostics combines diagnostic and therapeutic functions in a single platform (iron oxide nanoparticles for MRI and hyperthermia)
• Overcoming biological barriers:
  • Blood-brain barrier penetration (transferrin-functionalized nanoparticles)
  • Intracellular delivery of macromolecules (cell-penetrating peptides)
• Challenges and considerations:
  • Biocompatibility and biodegradability (silk fibroin scaffolds)
  • Scalability and manufacturing processes (microfluidic-based nanoparticle synthesis)
  • Regulatory and safety concerns (FDA guidelines for nanomedicine)