INTERMITTENT HORMONE DELIVERY SYSTEM

TO REDUCE STRESS IN LABORATORY ANIMALS, AND ULTIMATELY ALSO IN CLINICAL SETTINGS, CAMBRIDGE SCIENTIFIC, INC., PROPOSES TO REPLACE HORMONE DELIVERY PUMPS WITH IMPLANTABLE CAPSULES THAT RUPTURE AT PREDETERMINED TIMES, I.E., "PULSED" RELEASE. EXPERIMENTAL RESULTS TO DATE USING BIODEGRADABLE POLYMERS HAVE DEMONSTRATED THIS "BURST" PHENOMENON. FEASIBILITY WILL BE DEMONSTRATED IF, IN PHASE I, A POLYLACTIC/GLYCOLIC ACID POLYMER FORMULATION IS PREPARED WITH MECHANICAL PROPERTIES FAVORING PREDICTABLE BURSTS, AND A METHOD FOR PRODUCING IMPLANTS OF PRECISE SIZE AND POLYMER COATING THICKNESS IS DEMONSTRATED. PHASE I RESEARCH INCLUDES: (1) MEASURING YOUNG'S MODULUS, TENSILE STRENGTH, AND DIALYSIS PERMEABILITY OF POLYMER FORMULATIONS; (2) USINGTHE VALUES OF (1) TO DETERMINE OPTIMUM SIZE AND COATING THICKNESSES; (3) PRODUCING MODEL IMPLANTS; (4) SORTING IMPLANTS INTO PRECISE SIZE CATEGORIES; (5) PREPARING IMPLANTS WITH POLYMER; AND (6) MEASURING BURSTING TIMES OF CAPSULES WITH A SERIES OF COATING THICKNESSES. PHASE II WILL BE AIMED AT TESTING SELECTED HORMONES FOR INTERMITTENT RELEASE USING BOTH IN VITRO AND IN VIVO METHODSAND IN VIVO EVALUATIONS OF STRESS EFFECTS (I.E., HORMONAL ALTERATIONS) WITH THE MICROSPHERE-BASED PUMP ALTERNATIVE. THE OVERALL GOAL WILL BE THE VALIDATION OF IMPLANTABLE BURSTING CAPSULES AS A NOVEL PULSATILE HORMONE DELIVERY SYSTEM FOR RESEARCH AND CLINICAL APPLICATIONS; VALIDITY WILLBE MEASURED BY BOTH DELIVERY EFFICACY AND STRESS MODULATION.