Lecture 6 ProgrammedPulsed Drug Delivery and Drug Delivery in Tissue Engineering.pdf

Molecular Principles of Biomaterials Spring 2003
Lecture 6: Programmed/Pulsed Drug Delivery and Drug Delivery in Tissue
Engineering
Last time: principles of controlled release from solid polymers
Today: Pulsatile/regulated/multifactor controlled release:
3 case studies of controlled release
Reading: ‘Polymeric system for dual growth factor delivery,’ . Richardson et al., Nat. Biotech.
19, 1029-1034 (2001)
‘Microchips as controlled drug-delivery devices,’ . Santini et al., Andegwandte Chemie
Intl. Ed. 39, 2396-2047 (2000)
Regulated controlled release
Applications of regulated and pulsatile release
• Definition: release of cargo in bursts followed by periods of little/no release in a defined temporal pattern1
• Many applications would be best-served by non-monotonic and multi-cargo release profiles
o Motivation:
ƒ Single injection delivery of ‘booster’ for ination
ƒ Mimic natural secretion patterns of hormones
ƒ Provide optimal therapy for tolerance-inducing drugs
• Constant drug levels cause receptor down-regulation
ine boosting hormone release patterns in vivo
Lecture 5 – Programmed Drug Delivery 1 of 12
Molecular Principles of Biomaterials Spring 2003
ƒ Example: HIV-1 DNA ine delivered with boosters to elevate Ab titers2:
o Mechanical and electrical devices that can provide digitized release typically require larger devices and
surgical implantation (. Pharm. Res. 1, 237 (1984)); also have high cost
ƒ Show an example
o Degradable polymers allow submicron, injectable devices
• Two types
o Pre-programmed
ƒ Release profile is encoded in structure position of device
o Triggered
ƒ External signal drives release
Multilayer surface-eroding delivery devices
Case study: multilayered delivery devices3
polyphosphazene
slow-degrading
polylactide block
Fast-degrading Polyanhydride block
Hydrophilic PEG block
• Polyphosphazene:
o Base