Polymers eroding systems

To be useful as an implant, the polymer must hydrolyze to small, water soluble and toxicologically safe molecules and to be useful as a surface-eroding system, the hydrolysis must occur at much higher rates in the outer layers than it does in the bulk. Therefore, the successful development of such devices requires the selection of bonds that are capable of undergoing rapid hydrolysis. Two such bonds are anhydrides which are rapidly hydrolyzed to diacids even at the physiological pH of 7.4 and ortho esters which at pH 7.4 are slow to hydrolyze but which hydrolyze at increasingly rapid rates as the pH is lowered. Polymers based on both of these linkages are under intensive development and this chapter will cover, in depth, the development and current status of poly (ortho esters). 

Experiments were also performed to evaluate whether the extent of enhancement could be regulated externally. By varying the ultrasound intensity, the degree of enhancement for both polymer degradation and drug release for the bioerodible and non-erodible systems could be altered 10-fold (42). 

Chemically controlled release is governed by reactions that occur within polymer systems. In chemically controlled erodible systems, the drag release rate is controlled by degradation or dissolution of the polymer. In contrast to this, in pendent chain systems cleavage of polymer chains between the polymer network and a drag occurs via hydrolytic or enzymatic degradation (Peppas et al., 2000). 

The area of applied bioactive polymeric systems includes such diverse entities as controlled release systems (erodable systems, diffusion controlled systems, mechanical systems and microcapsules), and biologically active polymers, such as natural polymers, synthetic polypeptides, pseudo-enzymes, pseudo-nucleic acids and polymeric drugs. The area can also include immobilized bioactive materials, such as immobilized enzymes, antibodies and other bioactive agents and the area of artificial cells. This Chapter reviews the general field of biologically active synthetic and modified natural macromolecules with an emphasis on their common characteristics, problems and applications. The areas reviewed include both medical and non-medical applications for both controlled release systems and polymers that exhibit direct biological activity. 

The rate of drug release (E) from the eroding matrix is controlled by (a) the chemical properties of the system - the hydrolytic and the neutralizing process at the boundary of the device, catalytic degradation of the polymer and the intrinsic backbone reactivity, and (b) several concomitant physical processes such as water diffusivity, water solubility, water partitioning, etc. 

An erodible insert developed as a potential ocular drug-delivery system is marketed as a prescription drug for the lubricant properties of the polymer base. Lacrisert is a sterile ophthalmic insert used in the treatment of moderate to severe dry eye syndrome and is usually recommended for patients unable to obtain symptomatic relief with artificial tear solutions. The insert is composed of 5 mg of hydroxypropylcellulose in a rod-shaped form about 1.27 mm diameter by about 3.5 mm long. No preservative is used, since it is essentially anhydrous. The quite rigid cellulose rod is placed in the lower conjunctival sac and first imbibes water from the tears and after several hours forms a... 

When describing erosion of and drug release from surface erodible polymers, it is often implicitly assumed that the matrix erodes uniformly, thus resulting in a uniform release profile for a homogenously dispersed drug. While this may be a valid assumption for some homopolymer systems, neglecting the effects of crystallinity, some multicomponent... 

The past two decades have produced a revival of interest in the synthesis of polyanhydrides for biomedical applications. These materials offer a unique combination of properties that includes hydrolytically labile backbone, hydrophobic bulk, and very flexible chemistry that can be combined with other functional groups to develop polymers with novel physical and chemical properties. This combination of properties leads to erosion kinetics that is primarily surface eroding and offers the potential to stabilize macromolecular drugs and extend release profiles from days to years. The microstructural characteristics and inhomogeneities of multi-component systems offer an additional dimension of drug release kinetics that can be exploited to tailor drug release profiles. 

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