Microparticles Presentation

BSEN 416

MICROPARTicles

Zahraa Al-waeli

INDEX

What is a microparticle?

Preperation methods

Biomedical applications

Does size matter?

Drug releasing mechanism

Types of materials

Comparision to nanoparticles

Mechanical properties

Pros and cons

Surface properties

What is a microparticle?

• Spherical particles that have a diamter that ranges from 1-1000μm
• Used commonly as a biomaterial in biomedical applications, specifically drug delivery, tissue engineering and diagnostics.
• 1960s-1970s: First used in pharmaciutical applications
• 1980s-1990s: research for imaging and thearupitic delivery
• 2000's: tissue engineering and targeted therapies

Does size matteR?

• Impacts delivery route
• Drug delivery impact
• Cellular penetration
• Practical challenges
• Retention & stability

Material used for the synthesis of Microparticles:

Natural Polymers:

• Chitosan
• Alginate
• Dextran

Synthetic Polymers

• Poly(α-hydroxy acid)
• Poly(ε-caprolactone)
• Poly(ortho ester)
• Polyanhydrides
• Polyacetals
• PEGylation
• Smart polymers

Nonpolymeric Materials

• Lipids
• Liposomes

Mechanical and surface properties

*Microparticles have a diverse range of properties due to the different materials available for synthesis.

Preperation methods

Emulsifation

Single emulsifation :

• Polymer and drug are dissolved in solvent, the solution is than dispersed with mechanical agitation in an immiscible liquid.
• Used to encapsulate hydrophobic drugs
• Example: Making small capsules of Vitamin E (a hydrophobic drug) by mixing it with a biodegradable polymer and emulsifying it in water to form tiny particles for controlled release in skincare products

Double emulsifation:

• Requires an extra step but instead is used for hydrophilic drugs
• Example: Creating tiny particles that carry insulin (a hydrophilic protein) by mixing insulin with a polymer in oil, then emulsifying it again in water. This method protects insulin for use in diabetes treatment

Preperation methods

Microfluidic emulsion:

• Microparticles can be synthesized using techniques that manipulate the interaction between a continuous and dispersed phase to create uniform droplets
• T-junction: dispersed phase flows into a perpendicular channel, where the continuous phase exerts shear force to break it into droplets
• Flow focusing: the dispersed phase is surrounded and funneled by the continuous phase through a narrow channel, which increases shear force and enables precise droplet formation.
• Example: Using a microfluidic device to make perfectly uniform particles filled with a red dye for use in medical imaging. The setup ensures that each particle is the same size, making them ideal for testing in diagnostics.

Preperation methods

Coacervation phase separation

• Coacervation phase separation involves dissolving polymers in an organic solvent containing drug-loaded aqueous droplets. When the solution conditions or solvent system are altered, the polymer becomes insoluble and forms droplets. These polymer droplets then coat the surface of the aqueous drug droplets. Microparticles are formed by solidifying the polymer coating through processes like washing, centrifugation, and lyophilization, resulting in stable, encapsulated particles.

• Example: Encapsulating flavor oils (like peppermint oil) in gelatin. By changing the temperature, the gelatin separates and forms a shell around the oil droplets, creating tiny capsules used in chewing gum for flavor release:

Preperation methods

spray drying:

• Dispersion of drugs in a solvent system which is then sprayed through a fine nozzle into a chamber

• Example: Chitosan microparticles loaded with insulin for oral delivery. The insulin and chitosan solution is sprayed into a hot chamber, forming fine particles designed to protect insulin from degradation in the gastrointestinal tract.

Biomedical applications

Drug delivery systems

Vaccine Delivery:

• Controlled release: Microparticles can encapsulate drugs and release them in a controlled manner, improving therapeutic efficacy and reducing side effects

Example: PLGA can encapsulate doxorubicin

• Targeted delivery: Microparticles coated with antibodies or ligands can selectively bind to cancer cells, directly deliverying to tumors

• Adjuvents: Adjuvents can be loaded with microparticles to enhance immune response in vaccines, by providing a slow release mechaism for antigens.

Example: Hepatitis B or influenza

tissue engineering

• Microparticles can be used to create three-dimensional scaffolds for tissue engineering, providing a structure for cells to grow and regenerate tissues

Example: Collagen-based microparticles can be used to create porous scaffolds that mimic the extracellular matrix, facilitating cell attachment and growth for skin or cartilage regeneration

Biomedical applications

Bone regeneration:

Diagnostics applications

• Biosensors:

Example: Magnetic microparticles can be functionalized with antibodies to capture specific biomarkers (e.g., cancer antigens) for early cancer detection in blood samples.

• Imaging:

Example: Gold or silica-based microparticles can be loaded with imaging agents, enhancing the contrast in MRI or CT scans, improving the detection of tumors or abnormalities.

• Bone Fillers:

Example: Hydroxyapatite microparticles can be used as bone graft substitutes to fill defects and support new bone growth in orthopedic surgeries.

• Drug Delivery:

Example: Microparticles loaded with BMP-2 (Bone Morphogenetic Protein-2) can be implanted at bone defect sites to stimulate bone healing and regeneration

Wound healing:

• Therapeutic Release:

Example: Microparticles that release growth factors like PDGF (Platelet-Derived Growth Factor) can be used in chronic wound dressings to enhance healing rates and tissue regeneration.

• Biomaterial Coatings:

Example: Collagen microparticles can be incorporated into wound dressings to provide a moist environment and promote healing while reducing infection risk

Drug releasing mechanism:

Drug release from microparticles involves the migration of a drug from within the matrix or fromthe particle's surface to the surrounding environment

Swelling

Degredation

Diffusion

• Chemical breakdown (through hydrolysis or enzymatic cleavage) in a controlled manner.
• Two types:
• Surface erosion :

Occurs with hydrophobic polymers

• Bulk erosion:

Common in hydrophillic polymers

• Example:

Biodegradable sutures

• Occurs when the polymer matrix absorbs water causing it to swell.
• As the matrix expands, the polymer network mesh size increases, allowing the drug to diffuse out more rapidly
• Stimulus responsive polymers
• Example:

Hydrogel microparticles for insulin delivery

• Drug moves from inside the particle to the outside due to a chemical gradient.
• Factors influencing diffusion:
• Porosity
• Permeability
• Particle size
• Example:

PLGA microparticles releasing Doxorubicin

Comparision to nanoparticles: :

Disadvantages:

Advantages:

• Limited capacity
• Mechanical strength
• Complex design
• Cost of production

• Controlled release
• Versatile
• Biocompatible
• High surface area
• Enhanced stability
• Targeting capabilities

References:

1. Ayala-Somayajula, S.P. and Kompella, U.B. Subconjunctivally administered celecoxib-PLGA microparticles sustain retinal drug levels and alleviate diabetes-induced oxidative stress in a rat model. Eur. J. Pharmacol. 511, 191–198 (2005).
3. Black, K.A., Priftis, D., Perry, S.L., Yip, J., Byun, W.Y., and Tirrell, M. Protein encapsulation via polypeptide complex coacervation. ACS Macro Lett. 3, 1088–1091 (2014).
5. Bradley, M. and Vincent, B. Poly(vinylpyridine) core/poly(N-isopropylacrylamide) shell microgel particles: their characterization and the uptake and release of an anionic surfactant. Langmuir 24, 2421–2425 (2008).
7. Chen, Y. and Liu, L. Modern methods for delivery of drugs across the blood–brain barrier. Adv. Drug Deliv. Rev. 64, 640–665 (2012).
9. Lee, S., Yang, S.C., Heffernan, M.J., Taylor, W.R., and Murthy, N. Polyketal microparticles: a new delivery vehicle for superoxide dismutase. Bioconjug. Chem. 18, 4–7 (2007).
11. Li, Y. and Kohane, D.S. Microparticles. In: Wagner, W.R., Sakiyama-Elbert, S.E., Zhang, G., and Yaszemski, M.J. (Eds.), Biomaterials Science, 4th ed. Academic Press, 431–451 (2020).

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