Tuning polycaprolactone degradation for long acting implantables

Abstract

Polycaprolactone (PCL) is a bioresorbable polyester that has been widely used in biomedical applications since the 1970s. Because PCL undergoes bulk degradation, it is especially amenable to drug delivery applications. To ensure safety, a drug eluting implant must typically remain intact until the drug is exhausted, and following exhaustion the implant should breakdown and be resorbed. Many PCL based implants target delivery on the order of six months to one year, yet the time to degradation of PCLs is often on the order of multiple years. It is known that the time to degradation of PCL is directly related to its initial molecular weight; however, the limited integrity of neat low molecular weight PCLs make them unsuitable for implantation. Here we outline an approach to tune the time to degradation of PCL by blending low and high molecular weight polymers. We show that the degradation rate and permeability of PCL films are insensitive to their composition, and weight-average molecular weight (Mw) is predictive of time to fragmentation. Additionally, we demonstrate that compositions with up to 50 wt % low molecular weight polymer can retain the mechanical properties of a high molecular weight material. The resulting material has a lower effective Mw and a shorter time to degradation. In accelerated testing, it is possible to reduce time to degradation by roughly two-fold without sacrificing mechanical integrity. This provides versatility in adapting device designs to meet the needs of a specific application. These findings have implications in the development of biodegradable drug eluting implants, tissue engineering scaffolds, and resorbable surgical materials.