Poly tyrosine-derived polycarbonates

Particularly noteworthy are the tyrosine-derived polycarbonates (27), a family of polymers based on alkyl esters of desaminotyrosyl-tyrosine. The lead polymer in this family is poly[desaminotyrosyl-tyrosine ethyl ester (DTE) carbonate], a polymer derived from desaminotyrosyl-tyrosine ethyl ester. Other polymers in this series of tyrosine-derived polycarbonates are poly[desaminotyrosyl-tyrosine butyl ester (DTB) carbonate], poly[desaminotyrosyl-tyrosine hexyl ester (DTH) carbonate], and poly [desaminotyrosyl-tyrosine octyl ester (DTO) carbonate], where the letters B, H, and O indicate the presence of butyl, hexyl, or octyl ester pendent chains, respectively. 

Z. Dong, Synthesis of Four Structurally Related Tyrosine-Derived Polycarbonates and In Vitro Study of Dopamine Release from Poly(Desaminotyrosyl-Tyrosine Hexyl Ester Carbonate), Master s Thesis, Rutgers University, New Bnmswick, NJ, 1993. 

Poly(amino acids), poly(anhydrides), poly(caprolactones), poly(lactic/glycolic) acid cr lymers, poly(hydroxybutyrates), poly(orthoesters), tyrosine-derived polycarbonates... 

Johnson, P.A., et al. 2010. Interplay of anionic charge, poly (ethylene glycol), and iodinated tyrosine incorporation within tyrosine-derived polycarbonates Effects on vascular smooth muscle cell adhesion, proliferation, and motility. Journal of Biomedical Materials Research, Part A 93(2) 505-514. 

Pulapura, S., and J. Kohn. 1992. Tyrosine-derived polycarbonates backbone-modified pseudo -poly(amino acids) designed for biomedical appUcations. Biopolymers 32(4) 411-417. 

Pseudo-poly(amino acids) were first described in 1984 (Kohn, 1984) and have since been evaluated for use in several medical applications (Kohn, 1987 Yu-Kwon, 1989 Zhou, 1990 Kohn, 1993 Mao, 1993). Although a range of different pseudo-poly(amino acids) has been prepared, detailed studies of the physical properties, biological properties, and possible applications of these polymers have so far been conducted only for a select group of new tyrosine- derived polycarbonates, polyiminocarbonates, and polyarylates. This review will encompass the work to date on these specific materials. 

In vitro attachment and proliferation of fibroblasts on tyrosine-derived polycarbonates w as a function of the pendent chain length (Ertel, 1994). Consistent with the hypothesis that cells favor more hydrophilic and molecularly rigid surfaces, poly(DTE carbonate), the most hydrophilic and rigid of the surfaces tested (TaWte I), supported cell growth and proliferation better than the more hydrophobic poly(DTO carbonate). Poly(DTB carbonate) and poly(DTH carbonate) were intermediate in their ability to support ceU attachment and growth. 

The presence of a fibrous layer surrounding the PLA coupons is characteristic of a mild foreign body response. That such a fibrous layer was not formed at the bone/material interface for poly(DTE carbonate) and poly(DTH carbonate) is an important characteristic of these polymers. Intimate contact between bone and implant, even at 48 weeks post-implantation, is a strong indicator of the biocompatibility of the tyrosine-derived polycarbonates. 

Choueka,J., Char et,J.L., Koval, K.J., Alexander, H.,James, KS., Hooper, K.A. and Kohn,J. (1996) Canine bone response to tyrosine-derived polycarbonates and poly(L-lactic acid). /. Biomed. Mater. Res., 31, 35-41. 

Dong, Z. (1993) Synthesis of four structurally related tyrosine-derived polycarbonates and in vitro study of dopamine release from poly(desaminotyTosyI-tyrosine hexy l ester carbonate) MSc. Thesis, Rutgers University. ... 

Figure 2.17a shows an example of the neutron scattering that results when DjO is preferentially absorbed by one segment in a polymer. These data were obtained from a polymer in which poly(ethylene glycol), PEG, segments are randomly inserted along the polymer chains composed mostly of hydrophobic groups, tyrosine-derived polycarbonates... 

In dew of the nonprocessibility of conventional poly(L-tyrosine), which cannot be used as an engineering plastic, variational derivatives were emlsioned. The development of tyuosine-based polycarbonates, polyarylates and polyiminocarbonates represents the first time tyrosine-derived polymers wth favorable engineering properties have been identified. 

In an attempt to identify new, biocompatible diphenols for the synthesis of polyiminocarbonates and polycarbonates, we considered derivatives of tyrosine dipeptide as potential monomers. Our experimental rationale was based on the assumption that a diphenol derived from natural amino acids may be less toxic than many of the industrial diphenols. After protection of the amino and carboxylic acid groups, we expected the dipeptide to be chemically equivalent to conventional diphenols. In preliminary studies (14) this hypothesis was confirmed by the successful preparation of poly(Z-Tyr-Tyr-Et iminocarbonate) from the protected tyrosine dipeptide Z-Tyr-Tyr-Et (Figure 3). Unfortunately, poly (Z-Tyr-Tyr-Et iminocarbonate) was an insoluble, nonprocessible material for which no practical applications could be identified. This result illustrated the difficulty of balancing the requirement for biocompatibility with the need to obtain a material with suitable "engineering" properties. 

S.L. Bourke, J. Kohn, Polymers derived from the amino acid 1-tyrosine polycarbonates, polyarylates and copolymers with poly(ethylene glycol), Adv. Drug Deliv. Rev. 55 (2003) 447-466. 

Materials being developed include lactide/glycolide polymers, polyorthoesters, derivatives of pseudo-and poly-amino acids such as poly(l-glutamate), polyphosphazenes, poly(e-caprolactone) and tyrosine-polycarbonates. Advantages of these materials lies in their ease of processability and their biocompatibility with extracellular matrix components present in the body. They may be made as high surface area, porous devices thereby allowing cell movement and adhesion within the device both important for the assimilation of the material within the body and in the eventual replacement of the biodegradable component with the bodies own tissue. 

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