The encapsulation of ribozymes in biodegradable polymeric matrices.
Ribozymes are catalytic RNA that bind and cleave specific regions of target RNA. Therefore, protein synthesis by the target RNA may be specifically inhibited by ribozymes. However, ribozymes are rapidly cleared from plasma so effective treatment of proliferative diseases may rely on the repeated administration of these agents to maintain therapeutic ribozyme concentrations. Therefore, the objective of this study was to encapsulate ribozymes in injectable polymeric paste and microsphere formulations to allow for the controlled release of these agents over extended periods of time. Ribozymes were effectively encapsulated in poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic) (PLGA) microspheres in various size ranges using a modified water-in-oil-in-water emulsion system and in poly(epsilon-caprolactone) (PCL) pastes by physical blending. These formulations released non-degraded ribozymes, in vitro, in a controlled manner. PLLA microspheres released the ribozymes rapidly whereas PLGA released drugs more slowly. The release rate of ribozymes from PCL pastes could be effectively controlled by altering the loading concentration of ribozymes in the paste. These polymeric injectable formulations of ribozymes may allow for the extended treatment of localized disease sites, such as cancer and arthritis, without the need for repeated dosing.
Jackson
John K
JK
Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, 2146 East Mall, BC, Canada V6T 1Z3.
Liang
Linda S
LS
Hunter
William L
WL
Reynolds
Mark
M
Sandberg
Jennifer A
JA
Springate
Chris
C
Burt
Helen M
HM
D001673:Biodegradation, Environmental; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D006016:Glycolates; D019344:Lactic Acid; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D016337:RNA, Catalytic / Q000737:chemistry*
D003692:Delayed-Action Preparations; D006016:Glycolates; D011091:Polyesters; D011108:Polymers; D016337:RNA, Catalytic; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; D019344:Lactic Acid; C033616:poly(lactide)