Delivery Applications

ELPs are macromolecules composed of the monomeric pentapeptide (VPGXG), where X can be any amino acid residue except proline (18,19). Through variation in the length of the pol3uner and the residue in the X position, numerous polymers have been synthesized that exhibit sharp phase transitions, due to hydrophobic collapse and aggregation, when the temperature is raised above a temperatm-e termed the 

Intravenous administration of the thermally responsive ELP-rhodamine conjugate resiilted in localized precipitation in tumor tissue heated to 42°C, while no precipitation was observed when a control ELP-rhodamine conjugate, with a Tt of 70°C, was administered. Localized hyperthermia resiilted in a 2-fold increase in intratumoral accumulation 

As mentioned previously, ELPs can be further customized by combining different pentapeptide blocks, to produce block copolymers with sensitivity to several different temperatures (20,21). Block copolymers are of great interest for drug and gene delivery applications, significantly because of their ability to form micellar structures with the ability to encapsulate drugs or nucleic acids within the core, and to display targeting moieties on the periphery of the shell (29). 

Conticello and colleagues have studied the potential of amphiphilic diblock (AB) and triblock (ABA) elastin-like copolymers, where A is a hydrophilic and B a hydrophobic block, to reversibly self-assemble into well-defined micellar aggregates (20,30). Collapse of the hydrophobic block above Tt results in the formation of elastin-based nanoparticles. To provide diversity in the mechanical properties of the micellar structures, the amino acid sequence of the hydrophobic block was varied between plastic (VPAVG) and elastomeric (VPGVG) in nature. The hydrophilic block is designed to maintain solubility and form a protective core that prevents protein adsorption and clearance by the reticuloendothelial system. 

Reversible self-assembly into monodisperse spherical micellar particles, 50-90 nm in diameter, was observed for 

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In order to become useful dmg delivery devices, biodegradable polymers must be formable into desired shapes of appropriate size, have adequate dimensional stability and appropriate strength-loss characteristics, be completely biodegradable, and be sterilizahle (70). The polymers most often studied for biodegradable dmg delivery applications are carboxylic acid derivatives such as polyamides poly(a-hydroxy acids) such as poly(lactic acid) [26100-51-6] and poly(glycolic acid) [26124-68-5], cross-linked polyesters poly(orthoesters) poly anhydrides and poly(alkyl 2-cyanoacrylates). The relative stabiUty of hydrolytically labile linkages ia these polymers (70) is as follows ... 

Ranade, S.V., Richard, R.E., and Hehnus, M.N. Styrenic block copolymers for biomaterial and drug delivery applications, Acta Biomater., 1, 137, 2005. 

Recently, there has been significant interest in peptidomimetic forms of Tat49 57, not only because of its membrane translocation activity, but as a means of treating HIV infection [1]. Several peptoids, similar in sequence to Tat49 57, have been synthesized with the intention of preventing the HlV-Tat/Tar interaction, and thus preventing HIV replication [24, 25, 30, 31]. However, only recently has this class of peptoids been applied to membrane translocation and dmg delivery applications. 

For many drug delivery applications, the preferred method of delivery of the dosage form is by injection. For controlled release applications, the most frequently used approach to allow this method of administration is to prepare microspheres of the polymer containing the drug to be delivered. Several different techniques have been developed for the preparation of microspheres from polyanhydrides. 

It was therefore particularly inteipesting to investiage whether it would be possible to replace BPA by various derivatives of L-tyrosine as monomeric building blocks for the synthesis of poly-(iminocarbonates). In order to be practically useful in drug delivery applications, the replacement of BPA by derivatives of tyrosine must give rise to mechanically strong yet fully biocompatible polymers. 

Amphipathic peptides contain amino acid sequences that allow them to adopt membrane active conformations [219]. Usually amphipathic peptides contain a sequence with both hydrophobic amino acids (e.g., isoleucine, valine) and hydrophilic amino acids (e.g., glutamic acid, aspartic acid). These sequences allow the peptide to interact with lipid bilayer. Depending on the peptide sequence these peptides may form a-helix or j6-sheet conformation [219]. They may also interact with different parts of the bilayer. Importantly, these interactions result in a leaky lipid bilayer and, therefore, these features are quite interesting for drug delivery application. Obviously, many of these peptides are toxic due to their strong membrane interactions. 

N. Kossovsky, A. Gelman, E. Sponsler, H. Hnatyszyn 1994, (Surface modified nanocrystalline ceramics for drug delivery application), Biomaterials 15, 1201. 

Biodegradable polyurethanes have been proposed and studied before (9-72). The difference in our study is the inclusion of a phosphoester linkage instead of the commonly used polyester component. This seems to provide more flexibility as the side chain of the phosphate or phosphonate can be varied. For controlled drug delivery applications, drugs can be linked to this site to form a pendant delivery system. Moreover, for certain medical applications, fast degradation rate is obtainable by the introduction of these hydrolyzable phosphoester bonds. With the LDI based polyurethanes, drugs or other compounds of interest can also be coupled to the ester side chain of the lysine portion. 

Another class of environmentally sensitive materials that are being targeted for use in drug delivery applications is thermally sensitive polymers. This type of hydrogel exhibits temperature-sensitive swelling behavior... 

Poly(2-hydroxyethyl methacrylate) (PHEMA) has been the most widely used polymer in drug delivery applications. It is an extremely hydrophilic... 

In the last few years there have been new creative methods of preparation of novel hydrophilic polymers and hydrogels that may represent the future in drug delivery applications. The focus in these studies has been the development of polymeric structures with precise molecular architectures. Stupp et al. (1997) synthesized self-assembled triblock copolymer, nanostructures that may have very promising applications in controlled drug delivery. Novel biodegradable polymers, such as polyrotaxanes, have been developed that have particularly exciting molecular assemblies for drug delivery (Ooya and Yui, 1997). 

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... 

We have already mentioned a few of the polyanhydride chemistries that have been studied in drug delivery applications. Tables II through VII present some of the polyanhydrides that have been explored for drug... 

It is important to characterize the thermal properties of polyanhydrides that are proposed for drug delivery applications, as changes in crystallinity... 

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