Improving delivery of hydrophobic drugs from hydrogels through cyclodextrins.

A simple and effective technique of improving delivery of hydrophobic drugs from swellable systems is presented. Conventional methods of drug loading in hydrogel systems are limited by the characteristics of the pharmacological agent. The approach we present uses complexants to modulate drug release. Crosslinked poly(ethylene glycol) (PEG) hydrogels were synthesized, characterized, and used for vascular applications. The release of cyclosporine (CyA) from PEG hydrogels is significantly altered by the sterilization techniques. It was hypothesized that the release of CyA from PEG hydrogels can be modulated by using complexants. A cyclodextrin-CyA complex solution was prepared and used for drug loading. The sterilized PEG hydrogels that were loaded using the cyclodextrin-CyA complex solution had favorable release characteristics compared with the release from PEG hydrogels that were loaded using the conventional technique. Hence, drug release from swellable systems can be tailored by the application of this strategy.

Polymeric sustained local drug delivery system for the prevention of vascular intimal hyperplasia.

Anastomotic intimal hyperplasia (IH) is a major cause of both autologous vein and synthetic vascular graft failure. We have previously published data suggesting that cyclosporin may reduce the development of IH in a canine model. However, systemic administration of cyclosporin could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of cyclosporin from a polymeric vascular wrap will prevent the development of IH. To test this hypothesis, we developed a controlled release vascular wrap (sheet/ring) using a poly(ethylene glycol) (PEG) hydrogel. Sterilization of the polymers was performed using the ethylene oxide and hydrogen peroxide sterilization methods. It was found that except for one combination (8000 molecular weight and 1:1 crosslinking ratio), the differences in the swelling ratios for the sterilized and unsterilized hydrogels were not statistically significant. Release studies from unsterilized and ethylene oxide-sterilized PEG hydrogels were conducted. It was found that release lasted for approximately 50 h for sterilized as well as unsterilized PEG hydrogels. Acute animal studies, to test the deployment of both the polymeric sheets and rings to the adventitial surface of native arteries and veins, were completed successfully.

Sustained local drug delivery from a novel polymeric ring to inhibit intimal hyperplasia.

The long-term clinical success of autologous vein and synthetic vascular grafts are limited because of the development of anastomotic intimal hyperplasia (IH). We have previously published data suggesting that cyclosporine (CyA) may reduce the development of IH in a canine model (Hirko et al., J Vasc Surg 1993;17:877-887). However, systemic administration of CyA could create serious adverse effects. Therefore, it is our long-term goal to test the hypothesis that the controlled local release of CyA from a polymeric vascular wrap would prevent the development of IH. To test this hypothesis, we developed a controlled release polymeric ring that could be placed around anastomotic sites to deliver therapeutic drugs locally. The ring is a composite polymeric device consisting of poly(DL-lactide-co-glycolide) (PLGA) microspheres embedded in a poly(ethylene glycol) hydrogel. Several in vitro studies were conducted to evaluate the effects of different sterilization procedures on the properties of the device. It was determined that gamma sterilization was the preferred sterilization method of choice for this device. In vivo studies were conducted on a swine model to evaluate the biocompatibility of the ring. The histological findings of the ring implants at 2 and 4 weeks demonstrate the biocompatibility of this device.

Effects of sterilization on poly(ethylene glycol) hydrogels.

The past few decades have witnessed a dramatic increase in the development of polymeric biomaterials. These biomaterials have to undergo a sterilization procedure before implantation. However, many sterilization procedures have been shown to profoundly affect polymer properties. Poly(ethylene glycol) hydrogels have gained increasing importance in the controlled delivery of therapeutics and in tissue engineering. We evaluated the effect of ethylene oxide (EtO), hydrogen peroxide (H(2)O(2)), and gamma sterilization of poly(ethylene glycol) hydrogels on properties relevant to controlled drug delivery and tissue engineering. We observed that the release of cyclosporine (CyA) (an immunosuppressive drug that is effective in combating tissue rejection following organ transplantation) was significantly affected by the type of sterilization. However, that was not the case with rhodamine B, a dye. Hence, the drug release characteristics were observed to be dependent not only on the sterilization procedure but also on the type of agent that needs to be delivered. In addition, differences in the swelling ratios for the sterilized and unsterilized hydrogels were statistically significant for 1:1 crosslinked hydrogels derived from the 8000 MW polymer. Significant differences were also observed for gamma sterilization for 1:1 crosslinked hydrogels derived from the 3350 MW polymer and also the 2:1 crosslinked hydrogels derived from the 8000 MW polymer. Atomic force microscopy (AFM) studies revealed that the roughness parameter for the unsterilized and EtO-sterilized PEG hydrogels remained similar. However, a statistically significant reduction of the roughness parameter was observed for the H(2)O(2) and gamma-sterilized samples. Electron spin resonance (ESR) studies on the unsterilized and the sterilized samples revealed the presence of the peroxy and the triphenyl methyl carbon radical in the samples. The gamma and the H(2)O(2)-sterilized samples were observed to have a much higher concentration of the radical pecies when compared with the EtO and the unsterilized samples.

Dollars and sense: attributing value to a level I trauma center in economic terms.

BACKGROUND: Reliable, accurate, program-specific data for hospital product lines are often difficult to obtain. The purpose of this study was to determine the impact that trauma center status has on hospital net income when compared with other traditional hospital product lines and services. METHODS: Over a 3-year period, financial data were collected for 16 payor classes: 8 major payors for all injury diagnoses, in-patient and out-patient. These data were analyzed by total charges, total direct costs, contribution margin, and net income. A key assumption of this strategy was that although injury patients are treated at most hospitals, only trauma center status allows access to patients and provision of services that can contribute significantly to the bottom line. RESULTS: Over the 3-year period, the contribution margin increased for trauma patients (excluding Level I trauma), Level I trauma patients, and the combined population of trauma patients. The most significant portion of the increase resulted from patients seen as a result of trauma center status. CONCLUSION: We conclude that, for our institution, the investment in resources necessary to achieve and maintain trauma center status makes economic sense in that the trauma program contributes favorably to hospital net revenue.