BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Example: HIV-1 DNA vaccine delivered with boosters to elevate Ab titers2 o Mechanical and electrical devices that can provide digitized release typically require larger devices and surgical implantation(e.g Pharm. Res. 1, 237(1984); also have high cost Show an example o Degradable polymers allow submicron, injectable devices · Two types Release profile is encoded in structure and composition of device o Triggered External signal drives release Multilayer surface-eroding delivery devices >drug-loaded PEBP laver NHCHICONHOCOC&Hs )y fN-P o- poly phosphazene (NHCH2COOCH:CHJ PLCA coating p polyanhydride(PSP or PSTP) polylactide block m2.[o是mC ∞xwox,[o CH3 CHa Fast-degrading Polyanhydride block (xy-30: 70 by molar) Hydrophilic PEG block · Polyphosphazene Base-catalyzed degradation, acid-inhibited degradation ·PEG-b- Polyanhydride o Rapid bulk erosion-use hydrophilic block to make hrs-long degradation time for mm-thick caps(very fast o .. becomes porous during erosion, so need a means to prevent next layer from starting to degrade as ater reaches drug-containing layer o creates acidic byproducts as it degrades o First polyphosphazene layer degrades quickly( first burst release) o Polyanhydride layer: degrades quickly, acidifies internal environment Even though water penetrates the polyanhydride. A ne polyanhydride has completely adation of polyphosphazene begins and no drug is released from the polyphosphazene layer until eroded and acidic products are removed from microenvironment Lecture 5- Programmed Drug Delivery 2 of 12BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 ƒ Example: HIV-1 DNA vaccine delivered with boosters to elevate Ab titers2 : o Mechanical and electrical devices that can provide digitized release typically require larger devices and surgical implantation (e.g. 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 and composition of device o Triggered ƒ External signal drives release Multilayer surface-eroding delivery devices Case study: multilayered delivery devices3 Fast-degrading Polyanhydride block Hydrophilic PEG block polyphosphazene slow-degrading polylactide block • Polyphosphazene: o Base-catalyzed degradation, acid-inhibited degradation • PEG-b-Polyanhydride: o Rapid bulk erosion- use hydrophilic block to make hrs-long degradation time for mm-thick caps (very fast) o …becomes porous during erosion, so need a means to prevent next layer from starting to degrade as water reaches drug-containing layer o creates acidic byproducts as it degrades • Function of complete device: o First polyphosphazene layer: degrades quickly (first burst release) o Polyanhydride layer: degrades quickly, acidifies internal environment ƒ Even though water penetrates the polyanhydride, no degradation of polyphosphazene begins and no drug is released from the polyphosphazene layer until the polyanhydride has completely eroded and acidic products are removed from microenvironment Lecture 5 – Programmed Drug Delivery 2 of 12