Biodegradable hollow fibres of poly-L-lactic acid (PLEA) filled with a suspension of the contraceptive hormone levonorgestrel in castor oil were implanted subcutaneously in rats to study the rate of drug release, rate of biodegradation and tissue reaction caused by the implant. The in viva drug release was compared with the release in vitro using different release media. Fibres, disinfected with alcohol showed a zero-order release, both in vitro and in viva, for over 6 months. Fibres, either y-sterilized or disinfected with alcohol were harvested at time intervals ranging from 1 d to 6 months after implantation. Molecular weights of PLLA, tensile strengths, and remaining amounts of drug were determined as a function of time.The tissue reaction can be described as a very moderate foreign body reaction with the initial presence of macrophages, which are gradually replaced by fibroblasts which form a collagen capsule. Molecular weight determinations of PLEA showed a decrease from an initial M, of 1.59 X lo5 to 5.5 X 19" in 4 months (after alcohol sterilization). A gradual decrease in fibre strength with time was observed which did not significantly impair the release rate of levonorgestrel. Keywords: Drugs, controlled release, hollow fibre, biodegradable, poly-L-lactic acidThe development of improved methods of drug delivery has received a lot of attention in the last two decades. In many cases a constant effective non-toxic level of the drug at a particular body location is needed. To reach this goal many variations of controlled release have been investigated. These include the useof bioerodible matrices',' (from which the drug is released by controlled degradation of the top layers of the matrix), microspheres or even nanoparticles, with a polymer body, (from which the drug is slowly released)3 or controlled delivery by (mini) devices4.The methods mentioned above may have one or more disadvantages e.g. (i) either no zero-order release can be achieved, (ii) the appliance cannot, or not easily, be removed in case of an emergency, (iii) an operation is needed to insert the device, (iv), the materials used are not optimally biocompatible.Therefore a release system was developed with none of these disadvantages 5-7 i.e. a hollow fibre of poly-L-lactic acid (PLLA) containing the drug suspended in oil from which it is released at a zero-order rate. Its dimensions (1 cm long, diam. 0.7 mm) allow a simple application, using a syringe.Correspondence to Dr J.M. Schakenraad.Removal of the fibre can easily be performed by a small incision, in case of an emergency.In this paper we present the results of studies on the in vivo and in vitro release of levonorgestrel from hollow fibres, the rate of biodegradation of the fibre material, and the cell-biological evaluation as a response to the subcutaneous implantation of the fibre in rats. MATERIALS AND METHODS Fibres.The hollow fibres were spun from poly-L-lactic acid (M, 159 000) using a 'dry-wet' coagulation spinning process5* 6 . Molecular weight.After harvesting, the fibrou...

The basement membrane zone (BMZ) of the epithelium of the vocal folds was investigated electron microscopically in 10 patients suffering from various benign lesions and in 3 controls. Various defects were observed: a thickening by deposition of electron dense material, a loss of normal architecture, and a near absence of normal hemidesmosomes and anchoring fibers. Beside these previously reported phenomena, many vesicles carrying electron dense material were found near the plasma membrane. The vesicles were observed at various stages of fusion with the plasma membrane, on the other side of which their content was discharged. In the cytoplasm an increase of mitochondria was seen. The amount of condensed chromatin decreased while the nucleoli increased in comparison with the controls. These observations are suggestive of a hyperactivity of the basal cells of the epithelium in response to vibratory stress.

Dextran-magnetite particles (DMP) were studied for their use as a MR contrast agent to visualize lesions with a blood-brain barrier (bbb) disruption. A freezing injury to the rat cerebral cortex was used as a model of bbb disruption. The biodistribution of iv-injected DMP was studied using atomic absorption spectrophotometry, electron microscopy, and MRI. One hour after injection, focal accumulation of the particles in capillary endothelial cells could be demonstrated in the freezing lesion. Despite the observation that the relaxivity of DMP in vivo appears to be less well pronounced than that in vitro, the MR imaging studies show that DMP can be used to visualize bbb disruption with adequate contrast.

The high number of available wound dressings as well as the scientific reports about this topic indicates that the problem of an ideal wound dressing material is not jet solved. In the last 30 years lot of scientific reports about collagen as wound covering has been published. The positive effect of collagen by this application on a wound is well-known. We investigated the effect of a collagen sponge on healing of full thickness wound in rats. The animals were divided in two control and two experimental groups. In the control groups there were air exposed wounds as well as wounds covered with paraffin gauze. In the experimental groups the wounds were covered with natural reconstituted collagen sponge as well as with chemically prepared sponge. All results were compared. The wounds with collagen sponge covering healed significantly faster. Also the quality of the wound healing was better in the experimental groups.

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