Biodegradable hollow fibres for the controlled release of drugs

Abstract

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...

Particulate retrieval of hydrolytically degraded poly(lactide-co-glycolide) polymers

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Late degradation simulation of poly(I-Lactide)

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Copolymers of 1.5‐dioxepan‐2‐one and L‐ or D,L‐dilactide ‐ synthesis and characterization

“…Several commercial products are currently available in which poly(1actide) is a major component, either as a homopolymer or perhaps more commonly as a part in a copolymer. Surgical sutures, drug-delivery matrices and bone grafts are examples of applications that have been developed (5)(6)(7). Poly-L-lactic acid (PLLA) is a semicrystalline polymer with a glass-transition temperature (Tg) around 55OC (S), while poly-D,L-lactic acid (PDLLA) is amorphous, with a Tg in the same region (9).…”