Biodegradable hollow fibres for the controlled release of hormones

Poly(l-lactide), (PLLA), hollow fibres were prepared using a dry-wet phase inversion spinning process. The effect of several spinning parameters (i.e. bore medium flow rate, spinning dope extrusion rate, fibre take-up rate, and spinning height) on the hollow fibre dimensions is reported. The use of several spinning systems (i.e. different solvent/non-solvent pairs with or without additive) resulted in PLLA hollow fibres with varying asymmetric membrane structures, i.e. a porous matrix covered by an internal and external skin varying from very thick and dense to very thin and porous. Some of the differences in membrane structure were qualitatively explained on the basis of a model developed by Reuvers [52] for the formation of flat-sheet membranes by immersion precipitation. Release experiments were carried out using PLLA hollow fibres filled with a 25 wt.% dispersion of micronized 3H-levonorgestrel in castor oil, and a receiving fluid consisting of 40 wt.% aqueous ethanol. The hollow fibre levonorgestrel release rates were found to be dependent on the membrane structure of the hollow fibre wall. For the different hollow fibre samples, zero-order levonorgestrel release rates were found, in the range of 0.1–10 μg/cm/day. Possible release mechanisms are discussed. Preliminary in vivo (rabbit) release experiments showed that constant levonorgestrel blood plasma levels could be obtained for a period up to 210 days. It is concluded that the new biodegradable hollow fibre reservoir device shows very promising properties for possible application as a long-acting contraceptive delivery system

Biodegradable hollow fibres for the controlled release of drugs

Biodegradable hollow fibres of poly-l-lactic acid (PLLA) 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 vivo 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 vivo, for over 6 months. Fibres, either γ-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.\ud \ud 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 PLLA showed a decrease from an initial Mw of 1.59x10 5 to 5.5 × 10 4 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

DIX Domain Polymerization Drives Assembly of Plant Cell Polarity Complexes

The identities of cell polarity determinants are not conserved between animals and plants; however, characterization of a DIX-domain containing protein in land plants reveals that the physical principles of polar complex assembly are preserved across eukaryotes.</p