Jingwen Hou

Effects of amphiphilic PCL-PEG-PCL copolymer addition on 5-fluorouracil release from biodegradable PCL films for stent application.

Biodegradable film-based stents emerged as a promising medical platform for drug delivery to resolve stenosis encountered in physiological conduits (e.g. blood vessels, biliary and urethral tracts). Drug release kinetics significantly affects the pharmacological effects of a stent, thus it is desirable for a stent to possess highly adjustable drug release kinetics. In this study, a series of amphiphilic poly(ɛ-caprolactone)-poly(ethylene glycol)-poly(ɛ-caprolactone) (PCL-PEG-PCL) copolymers were used as additives to adjust 5-fluorouracil (5-FU) release from PCL films. The effects of the copolymer addition on drug release behavior, drug permeability, crystalline states, and surface and internal morphologies of the films were investigated. It was found that, the addition of PCL-PEG-PCL could accelerate 5-FU release. The release rate of 5-FU increased with increasing content of PCL-PEG-PCL in the film, but it decreased with the ratio of PCL blocks in the PCL-PEG-PCL copolymer. The diffusion test results showed that 5-FU diffused through the film containing PCL-PEG-PCL faster than it permeated through the pure PCL film, indicating that the addition of PCL-PEG-PCL can improve the permeability of 5-FU in PCL film. The addition of PCL-PEG-PCL copolymer showed high drug-release-regulating ability in the 5-FU-loaded PCL films.

Preparation, characterization and properties of partially hydrolyzed ethylene vinyl acetate copolymer films for controlled drug release

In this study, partially hydrolyzed ethylene vinyl acetate (EVA) copolymers with three hydrolysis degrees (12.2%, 32.6% and 46.9%) were obtained by alkaline hydrolysis of EVA copolymer, characterized by Fourier-transform infrared spectroscopy (FTIR), (1)H NMR and gel permeation chromatography (GPC). Paclitaxel-loaded and drug-free films based on the partially hydrolyzed EVA copolymers were fabricated. The swelling behaviors, crystallinities, mechanical properties of the fabricated films were investigated, and the effects of hydrolysis degree, film thickness and drug loading dose on in vitro drug release from the films were also investigated. In vitro swelling study showed that the swelling of partially hydrolyzed EVA films was greater than the EVA film and the film with higher hydrolysis degree swelled more intensively. X-ray diffraction (XRD) results exhibited that the crystallinity of the polymer increased with increasing hydrolysis degree. In paclitaxel-loaded EVA film, a part of paclitaxel was in crystalline form; while in paclitaxel-loaded partially hydrolyzed EVA films, paclitaxel was distributed in amorphous form or molecularly dispersed. In the in vitro drug release test, the film with higher hydrolysis degree and smaller thickness released paclitaxel more quickly. With higher drug loading dose, the drug release rate was larger. The partially hydrolyzed EVA films were applied for drug delivery systems for the first time, and demonstrated to have great capability of controlling drug release thanks to the adjustable hydrolysis degree.

Evaluation of two polymeric blends (EVA/PLA and EVA/PEG) as coating film materials for paclitaxel-eluting stent application

The ethylene vinyl acetate copolymer (EVA)/Poly (lactic acid) (PLA) blend and EVA/Poly (ethylene glycol) (PEG) blend were applied as the drug carrier materials for a bi-layer drug-loaded stent coating film, which consisted of a paclitaxel (PTX)-loaded layer and a drug-free EVA layer. The changes of weight and appearance of the drug-free polymeric blend films with increasing time were examined by X-ray diffraction analysis (XRD), gel permeation chromatography (GPC) tests and scanning electronic microscopy (SEM), and the results showed the degradation of PLA and the leaching of PEG from the films. The effects of PLA, PEG and drug contents on in vitro drug release were investigated, and the results demonstrated that the addition of PLA promoted the drug release while the addition of PEG almost did not. Franz cells diffusion test results indicated that the bi-layer structure successfully endowed the stent coating with the release of drug in a unidirectional fashion. The release profiles of films incorporated PTX and the mechanical performance of the film could be customized by readily adjusting the contents of the blend components. Therefore, the polymeric blends could be useful drug carrier materials for drug-loaded stent coating capable of releasing drug in a highly tunable manner.

Study on hydrophilic 5-fluorouracil release from hydrophobic poly(ϵ-caprolactone) cylindrical implants

Hydrophilic 5-fluorouracil (5-FU) loaded cylindrical poly(ϵ-caprolactone) (PCL) implants with different implant diameters (2, 4 and 8 mm), different drug loadings (25% and 50%) and end-capping were fabricated and characterized. The implant structure, drug content and molecular weight of PCL after 120 days drug release were investigated. The in vitro release results showed that, when the drug loading was the same, drug release was fastest for the implant with a diameter of 2 mm and slowest for the implant with a diameter of 8 mm; for the implants with the same diameters, the release of drug from the implants with 50% drug loading was faster than that from the implants with 25% drug loading; however, this effect of drug loading decreased with the increase of implant diameter; in addition, 5-FU was released slightly slower from the end-capped implants than from the corresponding uncapped implants; the drug release data for all the uncapped implants were best fit with the Ritger-Peppas model. Drug release from the hydrophobic implants was found to be dominated by diffusion mechanism. Scanning electron microscopy images and drug content measurements revealed that 5-FU release took place gradually from the exterior region to the interior region of the implants.

Incorporation of paclitaxel solid dispersions with poloxamer188 or polyethylene glycol to tune drug release from poly(ϵ-caprolactone) films

Here we report the application of solid dispersion (SD) technique to improve paclitaxel (PTX) release from poly(ϵ-caprolactone) (PCL)-based film. Paclitaxel solid dispersions (SDs) with either poloxamer188 (PXM) or polyethylene glycol (PEG) were successfully prepared by a melting method and then incorporated into PCL films, which were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD), differential scanning calorimetry (DSC) and In vitro drug release/dissolution studies. It was found that PTX was faster released from the SDs than the corresponding physical mixtures (PMs) or PTX alone. For the PCL films with almost the same PTX loading, drug release from films containing SDs was remarkably faster than that from the film directly incorporated with PTX particles, and the films containing SDs with PXM exhibited a faster drug release than those with PEG. An increase In the content of PXM had no significant influence on PTX release from the films containing SDs. Incorporation of a higher content of SDs led to slower drug release from PCL films, indicating that PTX loading had a dominating effect on drug release. Through this study, we demonstrated the feasibility of the application of SD technique on the improvement of PTX release from PCL films and offered some beneficial information on modulating drug release behavior by changing the compositions and contents of the SDs-loaded PCL films.

Treatments of paclitaxel with poly(vinyl pyrrolidone) to improve drug release from poly(ɛ-caprolactone) matrix for film-based stent.

Drug-loaded biodegradable films as a principal part of film-based stent were investigated for controlled drug delivery systems. In this study, solid dispersion technique, a pretreatment method of paclitaxel (PTX), was applied to prepare the PTX-loaded poly(ɛ-caprolactone) (PCL) films. Drug dissolution rates and characteristics of the poly(vinyl pyrrolidone) (PVP)/PTX solid dispersions (SDs) and physical mixtures (PMs) were investigated to show that the PVP/PTX SDs were successfully prepared before being incorporated in biodegradable films. Afterwards, the effect of the application of SDs on improving drug release behavior, weightlessness, crystalline states, and surface and internal morphologies of the films were studied. It was found that, the films with SDs showed a higher drug release rate than the films with PMs or pure PTX. In addition, the content of PVP in the SDs also had impact on drug release behavior: the more PVP in SDs, the faster the drug was released. According to the drug release test and weightlessness study, the possible drug release mechanism was put forward for the films with SDs. The application of solid dispersion technique showed a remarkable effect on improving drug release behavior for film-based biodegradable stent drug delivery systems.

Prevention of Schistosoma japonicum infection in mice with long-acting praziquantel implants.

This work reports the prevention outcomes of a praziquantel (PZQ) implant against the infection of Schistosoma japonicum in mice. The PZQ implant produced stable plasma PZQ concentrations in a range of 100-1300 ng/mL for a period of 70 days, by releasing PZQ in subcutaneous tissues in a sustained manner. To assess the prevention effects, the mice were infected at varying times after implantation. All the mice were sacrificed at 6 weeks after infection for worm and egg recovery and counting, worm morphological examination, determination of egg-hatching rates, and analysis of hepatic histology. The infection was successfully prevented for mice with early infection times (within 2-3 weeks), as nearly no worms, paired worms, eggs, or miracidia were recovered. However, in mice with late infection times (after 3 weeks), the prevention effects were diminished due to the decreased plasma PZQ concentrations at late times. Interestingly, the implants showed robust prevention effects on repeated infection at 1 and 3 weeks. In the infection-prevented mouse livers, no granuloma formation or granulomatous inflammation was observed. The results demonstrated that by blocking the development of infecting miracidia and by deactivating the eggs, the PZQ implants encouragingly prevented the S. japonicum infection and avoided liver damage.