Advanced Biomaterials - Drug Delivery

Drug Delivery Systems

Biomaterials-based drug delivery systems are sophisticated technologies that offer precise control over several critical factors in the administration of therapeutic agents. These include:

• Therapeutic agent release kinetics: The rate at which a drug is released into the body, which can significantly affect its efficacy and safety.

• Targeting: The ability to direct the drug specifically to the desired tissue or cellular target, thereby enhancing therapeutic effects while minimizing side effects.

• Bioavailability: The extent and rate at which the active ingredient or active moiety is absorbed and becomes available at the site of action.

These advanced systems utilize various biomaterial carriers such as nanoparticles, liposomes, or hydrogels to encapsulate immunomodulatory drugs, enhancing their transport and controlled release at the targeted site of action.

Biomaterial-based drug delivery systems can harness the enhanced permeability and retention (EPR) effect commonly observed in tumor environments. This biological phenomenon allows for passive accumulation of drugs within the tumor microenvironment, making these systems particularly effective for cancer therapy.

Therapeutic drugs play a significant role in the management of a wide range of medical conditions, including cancer, autoimmune disorders, and infectious diseases.

Forms of Drug Delivery:

Drug delivery can take various forms, which include:

1. Simple Oral Systems: These include solid forms like tablets, capsules, and liquid forms like syrups, which are widely used for their convenience and ease of administration.

   • Challenges: Oral delivery can be hindered by factors such as first-pass metabolism (the process where the concentration of a drug is greatly reduced before it reaches systemic circulation) and variable absorption rates in the gastrointestinal tract.

2. Transdermal Systems: These systems, such as ointments and patches, are designed for the delivery of drugs through the skin for systemic effects, circumventing the digestive system.

   • Benefits: They offer prolonged drug release and can provide a controlled and steady influx of medication into the bloodstream.

3. Intravenous Delivery: This method employs suspensions or nanoparticles to achieve rapid systemic effects. It provides a direct entry of the drug into the bloodstream, which is particularly useful in emergencies.

   • Considerations: Requires careful monitoring to avoid complications such as infection or irritation at the injection site.

Therapeutic Index

The therapeutic index of a drug is a critical concept in pharmacology that reflects the safety margin between the minimum effective concentration and the minimum toxic concentration of a drug.

• Therapeutic Index (TI): TI = (Minimum Toxic Concentration)/(Minimum Effective Concentration)

Understanding the therapeutic index is essential for optimizing drug dosages and individualizing treatment regimens to minimize adverse effects while maximizing therapeutic outcomes.

Drug Release Profiles

Drug delivery systems can have varied drug release profiles:

1. Conventionally Administered Single Dose: The drug exhibits rapid metabolism and distribution, leading to a quick rise in plasma concentration, which may subsequently decline exponentially.

   • Limitations: This can lead to sub-therapeutic levels or reach toxic levels if not properly managed.

2. Multiple Doses Administered at Regular Intervals: This method creates fluctuations in drug concentration in the plasma, often requiring careful scheduling and patient compliance.

   • Challenges: Erratic peaks can lead to side effects, and troughs may fall below effective levels, complicating therapy.

3. Controlled Release: The preferred approach for long-term therapies, controlled drug release maintains drug levels within the therapeutic index over extended periods. Implants releasing chemotherapeutic agents directly at tumor sites exemplify this approach, maximizing therapeutic impact while minimizing systemic toxicity.

   • Mechanisms: Controlled release involves zero-order kinetics, where the rate of drug release is constant regardless of concentration.

Different Types of Controlled Drug Delivery

There are several categories of controlled drug delivery systems:

1. Diffusion-controlled systems: Drug release is governed by the diffusion rate through a barrier.

   • controlled in the core of the device (reservoir) is surrounded by a polymer membrane

   • drug is delivered from the device through diffusion across the polymer membrane

   • Rate is controlled by thickness of membrane, characteristics, and porosity of the polymer membrane.

   • Porous vs non-porous

   • Non-Porous: Flux of the drug is defined by flicks first law of diffusion, since partition coefficient is used to describe the ratio of the drug concentration in the membrane, that is in equilibrium

2. Water-penetration-controlled systems: Drug release is regulated by the penetration of water into the polymer matrix, often linked to swelling or erosion processes.

   • Two types of control: Osmotic agent compartment & Drug compartment

   • Osmotic agent: filled with agent and pressure moves it

   • Drug compartment: filled with the drug that is to be delivered which contains laser drilled orifice, these two compartments are separated by a movable partition.

   • Depends on concentration and volume flux

3. Chemically-controlled systems: Involves drug release through chemical reactions like hydrolysis (the breakdown of compounds by reaction with water) or enzymatic degradation.

   • Polymer-drugs

4. Responsive systems: These systems react to external stimuli (e.g., pH, temperature) to release drugs in a controlled manner.

5. Particle-based systems: Include microparticles and nanoparticles which can facilitate targeted delivery and controlled release mechanisms, enhancing the therapeutic index and efficacy of the medication.

• Particle type: Micro and nanoparticles are used for their small size, allowing them to navigate biological barriers and reach specific target sites in the body.

• Drug mechanism is through diffusion

• Limitations - non-economical manufacturing methods

• burst released due to rupture of the exterior membrane. -Limitation

• Microspheres uniformly distributed in the polymer matrix

• Nano-shells: three different classes for nano drug deliveries

• Useful for target delivery such as in cancer targeting therapies

• Hydrogel systems: provide controlled release profiles, enhancing the efficacy of drug delivery while minimizing side effects.

• Gold is most preferred: bio-inert and good conductor