BEH.462/3. 962J Molecular Principles of Biomaterials Spring 2003 Lecture 5: Controlled release devices ast time: Using enzyme substrate and cytokine peptides to engineer biological recognition of synthetic polymer Tod controlled release devices and applications principles of controlled release devices based on degradable polymers Synthesis of controlled release devices Theory of polymer-based controlled release adin Materials for protein delivery in tissue engineering, S.P. Baldwin and W.M. Saltzman, Adv Drug Deliv. Rev., 33, 71-86(1998) Controlled Release Applications in Biological Engineering and Medicine Overview Controlled release: Cargo molecules( small molecule drug, protein, DNA, etc. )released to physiological environment at a designed rate why develop controlled release systems? o Recent estimates from FDA: -10 years and $150 to develop a single new drug product- looking for added alue o Many drugs have a narrow therapeutic index(difference between toxic level and therapeutic level Requires multiple injection Poor patient compliance ncreased incidence of infection and hemmorhages o Danger of systemic toxicity with more potent drugs; some drugs simply cannot be used IL-2 promotes lymphocyte proliferation, useful as an anti-cancer drug but toxic at systemic level (induces fever, pulmonary edema, and vascular shock) o Targeted delivery possible o Improves availability of drugs with short half lives in vivo Some peptides have half-lives of a few minutes or even seconds o Release systems can double as adjuvants for vaccines Show Figure 1 p 347 Ratner Where applicable Application Examples Active concentration of cargo Provide missing soluble factors Replace deficient human growth 1-10 pM; Hormones promoting cell differentiation, hormone in children 5-10nM growth, survival, or other functions Sustained or modulated delivery of Release of anti-cancer drugs at varies a therapeutic dru site of tumors to induce cancer Lecture 5- Controlled Release Devices 1 of 14BEH.462/3.962J Molecular Principles of Biomaterials Spring 2003 Lecture 5: Controlled Release Devices Last time: Using enzyme substrate and cytokine peptides to engineer biological recognition of synthetic polymers Today: controlled release devices and applications principles of controlled release devices based on degradable polymers Synthesis of controlled release devices Theory of polymer-based controlled release Reading: ‘Materials for protein delivery in tissue engineering,’ S.P. Baldwin and W.M. Saltzman, Adv. Drug Deliv. Rev., 33, 71-86 (1998) Controlled Release Applications in Biological Engineering and Medicine Overview • Controlled release: Cargo molecules (small molecule drug, protein, DNA, etc.) released to physiological environment at a designed rate • why develop controlled release systems? o Recent estimates from FDA: ~10 years and $150 to develop a single new drug product- looking for added value o Many drugs have a narrow therapeutic index (difference between toxic level and therapeutic level) ƒ Requires multiple injections ƒ Poor patient compliance ƒ Increased incidence of infection and hemmorhages o Danger of systemic toxicity with more potent drugs; some drugs simply cannot be used ƒ IL-2 promotes lymphocyte proliferation, useful as an anti-cancer drug but toxic at systemic level (induces fever, pulmonary edema, and vascular shock) o Targeted delivery possible o Improves availability of drugs with short half lives in vivo ƒ Some peptides have half-lives of a few minutes or even seconds o Release systems can double as adjuvants for vaccines • Show Figure 1 p. 347 Ratner Where applicable: Application Examples Active concentration of cargo Provide missing soluble factors promoting cell differentiation, growth, survival, or other functions Replace deficient human growth hormone in children 1-10 pM; Hormones 5-10 nM Sustained or modulated delivery of a therapeutic drug Release of anti-cancer drugs at site of tumors to induce cancer varies Lecture 5 – Controlled Release Devices 1 of 14