Delivery control

Small molecules can penetrate and penneate tlirough polymers. Because of this property, polymers have found widespread use in separation teclmology, protection coating, and controlled delivery [53]. The key issue in these applications is the selective penneability of the polymer, which is detennined by the diffusivity and the solubility of a given set of low-molecular-weight compounds. The diffusion of a small penetrant occurs as a series of jumps... 

Among other uses, these polymers have been employed in a variety of biomedical applications. Poly(phosphazenes) containing organic side chains, derived from the anaesthetics procaine and benzocaine, have been used to prolong the anaesthetic effect of their precursor drugs. They have also been used as the bioerodable matrix for the controlled delivery of drugs. 

Dunn, R. L., Lewis, D. H., and Goodson, J. M., MonoUthic fibers for controlled delivery of tetracycline, Proc. Int. Symp. Control. Rel. Bioact. Mater., 9, 157, 1982. 

The high permeability of PCL and its copolymers coupled with a controllable induction period prior to polymer weight loss (vide infra) lends itself to the development of delivery devices that are based on diffusion-controlled delivery of the drug during the induction period prior to weight loss. The subsequent biodegradation of the polymer serves the purpose of eliminating the need to recover the spent device. 

Goodson, J. M., Holborow, D., Dunn, R. L, Hogan, P., and Dunham, S., Monolithic tetracycline-containing fibers for controlled delivery to periodontal pockets, J. Periodontol., 54. 575-579. 1983. 

The biomedical uses of polyphosphazenes mentioned earlier involve chemistry that could in principle be carried out on a classical petrochemical-based polymer. However, in their bioerosion reactions, polyphosphazenes display a uniqueness that sets them apart. This uniqueness stems from the presence of the inorganic backbone, which in the presence of appropriate side groups is capable of undergoing facile hydrolysis to phosphate and ammonia. Phosphate can be metabolized, and ammonia is excreted. If the side groups released in this process are also metabolizable or excretable, the polymer can be eroded under hydrolytic conditions without the danger of a toxic response. Thus, poljnners of this tjT are candidates for use as erodible biostructural materials or sutures, or as matrices for the controlled delivery of drugs. Four examples will be given to illustrate the opportunities that exist. 

Juliano, R. L., and Me Cullough, H. N. (1980). Controlled delivery of an antitumor drug Localized action of liposome encapsulated cytosine arabinoside administered via the respiratory system, J. Pharmacol. Exp. Ther., 214, 381-387. 

In 2000, the first example of ELP diblock copolymers for reversible stimulus-responsive self-assembly of nanoparticles was reported and their potential use in controlled delivery and release was suggested [87]. Later, these type of diblock copolypeptides were also covalently crossUnked through disulfide bond formation after self-assembly into micellar nanoparticles. In addition, the encapsulation of l-anilinonaphthalene-8-sulfonic acid, a hydrophobic fluorescent dye that fluoresces in hydrophobic enviromnent, was used to investigate the capacity of the micelle for hydrophobic drugs [88]. Fujita et al. replaced the hydrophilic ELP block by a polyaspartic acid chain (D ). They created a set of block copolymers with varying... 

Kirby, C.J., Microencapsulation and controlled delivery of food ingredients. Food Sci. Technol. Today, 5, 74, 1991. 

Kiparissis Y, Akhtar P, Elodson PV, Brown RS. 2003. Partiton-controlled delivery of toxicants a novel in vivo approach for embryo toxicity testing. Environ Sci Technol 37 2262-2266. 

Reaction selectivity of the parent ortho-QM has also been explored with a variety of amino acid and related species.30 In these examples, the rates of alkylation and adduct yields were quantified over a range of temperatures and pH values. The initial QM3 was generated by exposing a quaternary benzyl amine (QMP3) to heat or ultraviolet radiation (Scheme 9.10). Reversible generation of QM3 was implied by subsequent exchange of nucleophiles at the benzylic position under alternative photochemical or thermal activation.30 Report of this work also included the first suggestion that the reversible nature of QM alkylation could be used for controlled delivery of a potent electrophile. 

This study has shown that typical coating biocides can be encapsulated within modified silica frameworks. These porous frameworks offer a means to inhibit the aqueous extraction of the biocide. In such combinations the biocides retain their anti-microbial properties, while controlled delivery facilitates a dynamic equilibrium to maintain a minimum inhibitory concentration at the coating interface, over an extended time period. There is evidence that biocide housed in such frameworks has a longer effective activity for a given initial concentration, since it is to some extent protected from the usual environmental degradation processes. 

There are many polymers which have been used as physical matrices for controlled delivery of drugs. In this paper, these polymers are separated into water-soluble, biodegradable, and nonbiodegradable materials. A description of each class of polymers is presented. Examples of polymers from each class that have been used as drug delivery matrices and the criteria for their selection are included in this general review. 

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