Bioerodable drug delivery

In bioerodible drug delivery systems various physicochemical processes take place upon contact of the device with the release medium. Apart from the classical physical mass transport phenomena (water imbibition into the system, drug dissolution, diffusion of the drug, creation of water-filled pores) chemical reactions (polymer degradation, breakdown of the polymeric structure once the system becomes unstable upon erosion) occur during drug release. 

Goldbart, R. Kost, J. Calcium responsive bioerodible drug delivery system. Pharm. Res. 1999,16, 1483-1486. 

V. Enzyme-based Bioartificial Polymeric Materials as Bioerodable Drug Delivery Systems... 

A second class of biodegradable polymers of interest are those used in the human (or animal) body. These polymers include those used in artificial organs, other implants, and controlled release devices for delivery of pharmaceuticals. Being placed in contact with the tissue environment, they can potentially biodegrade. In products such as biodegradable sutures and bioerodible drug-delivery matrices, such breakdown in the body may be undesirable. 

Because of possible adverse effects or a desire to terminate therapy, implanted bioerodible drug delivery systems should be easily removable at any time. For this reason, solid devices that maintain their mechanical integrity throughout the major portion of their delivery regime are particularly attractive. A further desirable feature is drug release that is close to zero order. 

Phosphazene polymers can act as biomaterials in several different ways [401, 402,407]. What is important in the consideration of skeletal properties is that the -P=N- backbone can be considered as an extremely stable substrate when fluorinated alcohols [399,457] or phenoxy [172] substituents are used in the substitution process of the chlorine atoms of (NPCl2)n> but it becomes highly hydrolytically unstable when simple amino acid [464] or imidazole [405-407] derivatives are attached to the phosphorus. In this case, an extraordinary demolition reaction of the polymer chain takes place under mild hydrolytic conditions transforming skeletal nitrogen and phosphorus into ammonium salts and phosphates, respectively [405-407,464]. This opens wide perspectives in biomedical sciences for the utilization of these materials, for instance, as drug delivery systems [213,401,405,406,464] and bioerodible substrates [403,404]. 

Polyphosphazenes can be considered as biomaterials in several different ways, depending on the type of utilization one can predict for these substrates. In this regard, we will consider three different topics concerning water-soluble POPs and their hydrogels, bioerodible POPs for drug delivery systems and for tissue engineering, and the surface implications of POP films. 

Skeletal Biocompatibility. Two Substituent Groups Attached to the Same Phosphazene Skeleton. Hydrolytical Instability 0 II — NH- CH2— C- OC2H5 Glycine or Lower Alkyl Aminoacid Esters Hydrolytically Unstable Polymers. Bioerodible Materials. Drug Delivery Systems. Tissue Engineering... 

Bioerodible polymers offer a unique combination of properties that can be tailored to suit nearly any controlled drug delivery application. By far the most common bioerodible polymers employed for biomedical applications are polyesters and polyethers (e.g., polyethylene glycol), polylactide, polyglycolide and their copolymers). These polymers are biocompatible, have good mechanical properties, and have been used in... 

Shen, E., Pizsczek, R., Dziadul, B., and Narasimhan, B. (2001), Microphase separation in bioerodible copolymers for drug delivery, Biomaterials, 22(3), 201-210. 

Siepmann, J., and Gopferich, A. (2001), Mathematical modeling of bioerodible, polymeric drug delivery systems, Adv. Drug Deliv. Rev., 48(2-3), 229-247. 

Heller, J. Baker, R.W. Theory and practice of controlled drug delivery from bioerodible polymers. In Controlled Release of Bioactive Materials Baker, R., Ed. Academic Press New York, 1980 1-17. 

The feedback-regulated drug delivery concept has been applied to the development of a bioerosion-regulated CrDDS by Heller and Trescony. " This CrDDS consists of a drug-dispersed bioerodible matrix fabricated from poly(vinyl methyl ether) half-ester, which was coated with a layer of immobilized urease (Fig. 26). In a solution with near neutral pH, the polymer only erodes very slowly. In the presence of urea, urease at... 

Fig. 26 Cross-sectional view of a bioerosion-regulated hydrocortisone delivery system, a feedback-regulated drug delivery system, showing the drug-dispersed monolithic bioerodible polymer matrix with surface-immobilized ureases. The mechanism of release and time course for the urea-activated release of hydrocortisone are also shown. (From Ref > 1)...

Polyanhydrides are a class of bioerodible polymers that have shown excellent characteristics as drug delivery carriers. The properties of these biomaterials can be tailored to obtain desirable controlled release characteristics. Extensive research in this promising area of biomaterials is the focus of this entry. In the first part of the entry, the chemical structures and synthesis methods of various polyanhydrides are discussed. This is followed by a discussion of the physical, chemical, and thermal properties of polyanhydrides and their effect on the degradation mechanism of these materials. Finally, a description of drug release applications from polyanhydride systems is presented, highlighting their potential in biomedical applications. 

H.B. Rosen, J. Chang, G.E. Wnek, R.J. Lin-hardt and R. hanger, Bioerodible polyanhydrides for controlled drug delivery. Biomaterials 1983, 4, 131-133. 

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