Compressed poly(vinyl alcohol)-polycaprolactone admixture as a model to evaluate erodible implants for sustained drug delivery.
An implant may release a drug either by diffusion concurrent with dissolution of the polymeric implant material without depolymerization (Type A) or by bioerosion involving depolymerization (Type B). The Type A material may induce immune response, while the erosion of Type B polymer releases fragments which could cause toxicity problems. It is proposed that a combination of the two types of polymers may attenuate the intensity of immune response and toxicity, because the presence of one in an implant of the same weight reduces the amount of the other. However, it is important to determine first, if sustained delivery may be achieved by such an implant. In this study, partially hydrolyzed poly(vinyl acetate) (PVA) and polycaprolactone (PCL) were chosen as the model Type A, and B polymers, respectively, to evaluate this objective in vitro. Pellet discs were prepared to assess the effects of compression, proportion of PVA to PCL, acetyl content of PVA, PCL hydrolysis catalyst and drug loading, using methylene blue (MB) as a model drug. Results showed that sustained delivery could be effected, but PCL erosion did not occur as planned. Therefore, PCL served only as a passive component of the implant, while PVA was eroded with the release of MB. Consequently, it was inferred that a polymer may not be required as a passive component, which suggested the use of other compounds of known biocompatibility. Tests with insulin in a compressed solid admixture with cholesterol showed that reduction of hyperglycemia in diabetic Wistar rat could be effected reproducibly for at least 2 weeks. Thus, the present study, originally planned to test a proposed concept, indicates that many nonpolymeric materials of known biocompatibility may be suitable for drug delivery implants as well.
Wang
P Y
PY
Institute of Biomedical Engineering, Faculty of Medicine, University of Toronto, Canada.
D000818:Animals; D001673:Biodegradation, Environmental; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy*; D004343:Drug Implants; D007328:Insulin / Q000008:administration & dosage* / Q000627:therapeutic use; D008299:Maleic Anhydrides; D008751:Methylene Blue; D011091:Polyesters; D011142:Polyvinyl Alcohol; D051381:Rats; D011919:Rats, Inbred Strains
D001786:Blood Glucose; D004343:Drug Implants; D007328:Insulin; D008299:Maleic Anhydrides; D011091:Polyesters; D011142:Polyvinyl Alcohol; D008751:Methylene Blue