Implants bioerodible

Grossman, S. A., Reinhard, C., Colvin, O. M., Chasin, M., Brundrett, R., Tamargo, R., and Brem, H., The intracerebral distribution of BCNU delivered by surgically implanted bioerodable polymers. Submitted. 

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. 

The principal focus of our work is the development of a sub-dermally implantable, bioerodible monolithic device that would release contraceptive steroids by close to zero order kinetics for at least six months. Also, polymer erosion and drug release should be coupled so that no pol3iTner remains in the tissue after all the drug has been released. 

Poly(anhydrides). Poly(anhydrides) are another class of synthetic polymers used for bioerodible matrix, dmg dehvery implant experiments. 

The development of a bioerodible implant capable of releasing controlled amounts of a contraceptive steriod from a subcutaneous implant for periods of time ranging from three months to about a year has been in progress for many years. The three principal bioerodible polymers currently in use are copolymers of lactic and glycolic acid (25), poly(e-caprolactone) (26), and poly (ortho esters) (14). The desire to develop such a contraceptive system was the principal motivation for the initial development of the poly(ortho ester) polymer system. 

Some implantation devices have extended well beyond the classic diffusional systems and have included not only bioerodible devices, but also implantable therapeutic systems that can be activated. There are devices activated by change in osmotic pressure to deliver insulin [225], morphine release trigger by vapor pressure [226], and pellets activated by magnetism... 

Busch, O., Solheim, E., Bang, G., and Tomes, K. (1996). Guided tissue regeneration and local delivery of insulinlike growth factor I by bioerodible polyorthoester membranes in rat calvarial defects. Int. J. Oral Maxillofac. Implants, 11, 498-505. 

Figure 3.21 Bioerodable polymers can be used for the controlled release of pharmaceutical molecules (black clipscs). Ideally, hydrolysis of the implanted matrix polymer should occur at the polymer surface only so that the drug molecules are released at a constant rate—a so-called zero-order release profile.

Gopferich, A. Bioerodible implants with programmable drug release. J. Contr. Rel. 44 271-281, 1997. 

The availability of polymers having different delay times makes possible the construction of devices that can release proteins in well defined and well spaced pulses. To do so, it is only necessary to use a device that contains two or more different polymer formulations in separate domains. This can be achieved by placing these formulations in a thin, bioerodible, macroporous cylinder for subsequent implantation, or better, t.o encapsulate each formulation in a bioerodible, macroporous membrane. In this latter approach, desired release profiles can be achieved by using appropriate mixtures of different capsules. 

Semi-solid bioerodible implant materials would enable the delivery of soft implants with a needle and syringe. Heller introduced such a material, poly(orthoester) IV, that shows long residence time after subconjunctival administration, an erosion-controlled drug release, and ocular biocompatibility. Depending on the ocular site of injection, the ocular lifetime of the drug ranges from 5 to 6 months. 

Most bioinert rigid polymers are commodity plastics developed for nonmedical applications. Due to their chemical stability and nontoxic nature, many commodity plastics have bwn used for implantable materials. This subsection on rigid polymers is separated into bioinert and bioerodable materials. Table 11.6 contains mechanical property data for bioineit polymers and is roughly ordered by elastic modulus. Polymers such as the nylons and poly(ethylene terephthalate) slowly degrade by hydrolysis of the polymer backbone. However, they are considered bioinert since a significant decrease in properties takes years. 

Poly (hexamethylene adipimide) is also known as Nylon 6,6 since its repeat unit has two six-caibon sequences. Nylon is tough, abrasion resistant, and has a low coefficient of friction, making it a popular suture material. Nylon 6,6 is hydrophilic and absorbs water when placed in tissues or in humid environments (9 to 11 percent water when fully saturated ). Absorbed water acts as a plasticiser, increasing the ductility and reducing the modulus of Nylon 6,6. Nylon bioerodes at a very slow rate. Nylon 6,6 implant in dogs lost 25 percent of its tensile strength after 89 days and 83 percent after 725 days. ... 

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. 

Bioerodible implant. Insulin is formulated in a polymer that dissolves in tissue at a given rate. Once implanted in the tissue, insulin is released into the body at a rate determined by the rate at which the polymer dissolves. 

Performance parameter Injection Oral Iontophoresis Nasal Bioerodible implant [nfusion pump IV microparticle Ultrasound... 

S.R. Chennamaneni, C. Mamalis, B. Archer, Z. Oakey, and B.K. Ambati, Development of a novel bioerodible dexamethasone implant for uveitis and postoperative cataract inflammation, / Control Release, 167,53-59,2013. 

Bioerodable materials in current use are limited to applications that do not require long-term strength retention. It is acknowledged by the medical profession that problems exist with the current practices of bone fracture fixation. Two serious problems are osteoporosis due to stress shielding [1-3] and necessary second operations for device removal after bone healing. To alleviate these problems, polymers of a-hydroxy acids such as lactic and glycolic acid are being explored. They have shown potential utility as biocompatible, fully resorbable implant devices. The biocompatibility of poly(a-hydroxy acids) has been known for some time from in vivo acute and subacute tissue reaction [4], as well as in vitro cytotoxicity response [5]. Sutures of these materials have been in use now for many years. 

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