Development of self-deployment and drug release polymeric film device

摘要

Introduction: The design of drug-delivery systems (DDS) targeting a local specific organ in body, e.g., bladder and subretinal structure, is one of the most challenging tasks. It is ideal for DDS devices to be less-invasive as much as possible. Given the conventional DDS devices, DDS microspheres are superior in terms of less-invasive by injection but they cannot be located at the affected area. On the other hand, sheet type DDS devices require surgical procedure to retain in the body while they can delivery drug for long-term at affected area. Therefore we aimed at developing of DDS device that can be injected and located at the affected area for long-term drug release. We made the DDS devices by embedding DDS microspheres in polymeric film. Herein, we report the fabrication of device, microspheres distribution in the film, release characteristics and self-deployment. Material and Method: Collagen microspheres (COLs) were made by water-in-oil emulsion method. And COLs were immersed in solution of a model drug FITC-dextran {FD-40). The devices were made by photopolymerization with UV light of mixtures of polyethylene glycol dimethacrylate (PEGDM), a photopolymerization initiator and COLs (Fig. 1). The devices were observed by SEM and fluorescence microscope to reveal the distribution of COLs in PEGDM. In vitro release study was carried out to reveal release characteristics. To estimate the amounts of FD-40 that had diffused out of the devices, the devices were immersed in 3 mL of PBS and incubated at 37 C. The fluorescent intensities of the PBS solutions were measured spectrofluorometrically. PEGDM sheets of different thickness were photopolymerized with UV light. They were rounded several times around a glass cylindrical shape and the deployment times were measured in water in order to examine self-deployment characteristics. Result and Discussion: COLs were uniformly distributed in the device (Fig.2) and a part of COLs was exposed on the surface of the device. In vitro release study confirmed that devices could release FD-40 continuously over 10 days. Additionally, release characteristics changed matrix type by increasing the concentration of COLs in the device. PEGDM sheets showed a linear relationship between deployment time and the number of turns of the sheet until it is fully expanded. These observations and Fig. 3 indicate the injectability of this device. Conclusion: We developed a new DDS device targeting a local specific organ, which can be injected and release drugs over 10 days. This device can provide less-invasive and long-term locally drug release. Embedding DDS microspheres in thin film has great promise to efficacious treatment.