Lecture 22 - Sustained Release of Factors from Polymeric Biomaterials

Question 1

Patient Benefits of Implant for Drug Release

Answer 1

• Reduce pain associated with injection
• Less inconvenience with remembering to take medication
• Possibility of targeting specific tissues or organs

Question 2

Loading Drugs into Polymers

Answer 2

• Mix the drug into the polymer during formation
• Infuse the drug into polymer after formation
• Fickian diffusion
• Microvoid diffusion

Question 3

Mixing Drug into Polymer During Formation

Answer 3

• Dissolve drug in solvent and cast
• Microencapsulation (solution of polymer, solution of drug)
• Melt and injection mold (mix drug in with molten polymer)
• Heat and extrusion (higher MW/viscosity process)
• Melt/solvent with fiber spinning (macro scale)
• Electrospinning (nano scale)
• Concerned with ensuring drug stays active (exposed to high temps, solvents)

Question 4

Infusing Drug into Polymer After Formation

Answer 4

• Lower T, could preserve drug activity
• Super critical or subcritical CO2 (adds pores)
• CO2 goes from gas to liquid (good solvent), liquid CO2 swells broad range of amorphous polymers
• Results in plasticized polymer —> increased chain motion, increased free volume, increased diffusivity, incorporate drug solution into polymer and preserves drug structure and function
• Release of pressure often foams the structure (release slow to avoid entrapment of bubbles on inside)

Question 5

Incorporate Drugs: Fickian Diffusion

Answer 5

• Polymer and glass frit soaked with drug solution
• 1) Pressurize (super critical-31C and 1070 PSI)
• 2) Swell (same # of chains, larger volume)
• 3) Impregnate (pressure maintained, concentration gradient of drug)
• 4) Depressurize

Question 6

Incorporate Drugs: Microvoid Diffusion

Answer 6

• Polymer and glass frit soaked with drug solution
• 1) Pressurize (super critical-31C and 1070 PSI)
• 2) Swell (nonuniform swelling)
• 3) Impregnate (small domains of higher concentration of drug)
• 4) Depressurize (domains left behind)

Question 7

Disadvantages of Drug Delivering Implants

Answer 7

• Requires an implantation surgery

- Surgeries vary in level of invasiveness

Question 8

In Situ Forming Implant

Answer 8

• In place, in position
• Less invasive
• Provide constant plasma-level time profiles —> reduce peaks and valleys (no sawtooth areas where no drug activity), provide appropriate dosing when level range is narrow
• Provide localized or systematic delivery for 1-4 months

Question 9

Types of In Situ Forming Implants

Answer 9

• Thermoplastic pastes
• Polymer precipitation
• Thermally induced gelling

Question 10

Thermoplastic Pastes

Answer 10

• Semi-solid polymer injecting
• Forms depot upon cooling
• Requires low T_m, T_g of polymer (prevents tissue damage, need polymer to flow)
• Drugs can be incorporated by simple mixing
• Common uses: surgical site (can be added during surgery), subcutaneous injection (need shallow injection to maintain T of polymer as injected - polymer cools)

Question 11

Polymer Precipitation

Answer 11

• Water insoluble, bio-degradable polymer in organic solvent (drug added to solution)
• Injected into body —> water infiltrates polymer solution causing phase separation from solvent, results in depot at site of injection
• Burst release —> initial burst release is common (a lot of drug comes out with organic solvent during phase separation), directly related to phase inversion
• Deliver with least amount of damage to drug, tissue surrounding

Question 12

Thermally Induced Gelling

Answer 12

• Utilize lower critical solution temperature —> phase transition between solution and gel
• Multiple polymer systems exhibit this behavior —> few are biocompatible, PEG-PLA-PEG (MW very definitive), PLGA-PEG-PLGA (solutions at room temp injected into body
• Temperature cause gelation and hydrophobic molecules within solution released to help gelation