Toxicity, biodegradation and elimination of polyanhydrides

Katti, Dhirendra S.; Lakshmi, Seetha; Langer, Robert; Laurencin, Cato T.

doi:10.1016/s0169-409x(02)00052-2

Cited by 282 publications

(223 citation statements)

References 45 publications

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“…First, there is interest in discerning the effect of device geometry (films vs nanospheres) on protein release kinetics. As mentioned before, 3,42,48,49 polyanhydride devices of various geometries have been tested for in vivo applications, and the high throughput method provides a rapid way to simultaneously study the effects of polymer chemistry and device geometry. Second, it is important to demonstrate that the fluorescence technique is amenable to various device geometries.…”

Section: Resultsmentioning

confidence: 99%

Novel, High Throughput Method to Study in Vitro Protein Release from Polymer Nanospheres

2009

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Controlled delivery of therapeutic protein drugs using biodegradable polymer carriers is a desired characteristic that enables effective, application-specific therapy and treatment. Previous studies have focused on protein delivery from polymers using conventional "one-sample-at-a-time" techniques, which are timeconsuming and costly. In addition, many therapeutic proteins are in limited supply and are expensive, so it is desirable to reduce sample size for design and development of delivery devices. We have developed a rapid, high throughput technique based on a highly sensitive fluorescence-based assay to detect and quantify protein released from polyanhydrides while utilizing relatively small amounts of protein (âˆ¼40 Î¼g). These studies focused on the release of a model protein, Texas Red conjugated bovine serum albumin, from polyanhydride copolymers based on sebacic acid (SA) and 1,6-bis(p-carboxyphenoxy)hexane (CPH). The protein release profiles were assessed simultaneously to investigate the effect of polymer device geometry (nanospheres vs films), polymer chemistry, and pH of the release medium. The results indicated that the nanosphere geometry, SA-rich chemistries, and neutral pH release medium led to a more rapid release of the protein compared to the film geometry, CPH-rich chemistries, and acidic pH release medium, respectively. This high throughput fluorescence-based method can be readily extended to study release kinetics for other proteins and polymer systems. KeywordsBovine serum albumin, drug carrier, fluorescent dye, nanosphere, plasma protein, polymer, combinatorial chemistry, cattle Controlled delivery of therapeutic protein drugs using biodegradable polymer carriers is a desired characteristic that enables effective, application-specific therapy and treatment. Previous studies have focused on protein delivery from polymers using conventional "one-sample-at-a-time" techniques, which are time-consuming and costly. In addition, many therapeutic proteins are in limited supply and are expensive, so it is desirable to reduce sample size for design and development of delivery devices. We have developed a rapid, high throughput technique based on a highly sensitive fluorescence-based assay to detect and quantify protein released from polyanhydrides while utilizing relatively small amounts of protein (∼40 µg). These studies focused on the release of a model protein, Texas Red conjugated bovine serum albumin, from polyanhydride copolymers based on sebacic acid (SA) and 1,6-bis(p-carboxyphenoxy)hexane (CPH). The protein release profiles were assessed simultaneously to investigate the effect of polymer device geometry (nanospheres vs films), polymer chemistry, and pH of the release medium. The results indicated that the nanosphere geometry, SA-rich chemistries, and neutral pH release medium led to a more rapid release of the protein compared to the film geometry, CPH-rich chemistries, and acidic pH release medium, respectively. This high throughput fluorescence-based method can be readily exten...

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Section: Resultsmentioning

confidence: 99%

Novel, High Throughput Method to Study in Vitro Protein Release from Polymer Nanospheres

2009

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“…[1][2][3][4] The drug release profiles from polyanhydride carriers can vary from days to months depending on the polymer chemistry, drug partitioning, and drug loading. The degradation via hydrolysis into their acidic monomers takes a period of months for poly(CPH), weeks for poly(SA), 5,6 and days for poly(CPTEG). 7 Previous work has shown an important relationship between polymer microstructure and drug release kinetics of the CPH:SA polyanhydride system.…”

Section: Introductionmentioning

confidence: 99%

Identifying Factors Controlling Protein Release from Combinatorial Biomaterial Libraries via Hybrid Data Mining Methods

et al. 2010

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Polyanhydrides are a class of degradable biomaterials that have shown much promise for applications in drug and vaccine delivery. Their properties can be tailored for controlled drug release, drug/protein stability, and immune regulation (adjuvant effect). Identifying the relationship between the molecular structures of the polymers and the drug release kinetics profiles would help understand the release mechanism and aid in the accurate prediction of drug release and the rational design of polymer-based drug carrier systems. The molecular structure descriptors that had the most impact on the release kinetics were identified using a prediction/optimization data mining approach. Using this new approach for modeling nonlinear release kinetics behavior, we determined that the descriptors which had the greatest effect on the release kinetics were the number of backbone -COO-nonconjugated bonds, the number of aromatic rings, and the number of -CH 2-bonds. ABSTRACT: Polyanhydrides are a class of degradable biomaterials that have shown much promise for applications in drug and vaccine delivery. Their properties can be tailored for controlled drug release, drug/protein stability, and immune regulation (adjuvant effect). Identifying the relationship between the molecular structures of the polymers and the drug release kinetics profiles would help understand the release mechanism and aid in the accurate prediction of drug release and the rational design of polymer-based drug carrier systems. The molecular structure descriptors that had the most impact on the release kinetics were identified using a prediction/optimization data mining approach. Using this new approach for modeling nonlinear release kinetics behavior, we determined that the descriptors which had the greatest effect on the release kinetics were the number of backbone -COO-nonconjugated bonds, the number of aromatic rings, and the number of -CH 2 -bonds.

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“…[1][2][3]. The extensively investigated biodegradable polymers for controlled drug delivery applications include polyesters, polyanhydrides, polycyanoacrylates, poly(amino acid), poly(ortho ester), polyphosphazenes, etc.…”

Section: Introductionmentioning

confidence: 99%

Characterization and in vitro degradation of poly(octadecanoic anhydride)

Dong

Zhang

Jiang

et al. 2007

J Mater Sci: Mater Med

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Poly(octadecanoic anhydride) (POA) has been prepared by melt polycondensation of octadecanoic diacid. POA was characterized by Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and wide angle X-ray diffraction (WAXD). The results of in vitro degradation and SEM micrographs show that the erosion process of POA is neither bulk nor perfect surface erosion but rather has elements of both in phosphate buffer at 37°C. The moving erosion front is characteristic of surface erosion whereas the remaining porous shell stems from bulk erosion. While a significant special degradation property of POA is that POA presents a very slow degradation rate in acidic condition (pH 5.98), only 1.64% weight loss for 20 days, and it completely degrades after 18 days in basic buffer (pH 7.4). Comparing with poly(sebacic anhydride) (PSA), POA has the higher crystallization degree, and the slower hydrolytic rate.

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Toxicity, biodegradation and elimination of polyanhydrides

Cited by 282 publications

References 45 publications

Novel, High Throughput Method to Study in Vitro Protein Release from Polymer Nanospheres

Novel, High Throughput Method to Study in Vitro Protein Release from Polymer Nanospheres

Identifying Factors Controlling Protein Release from Combinatorial Biomaterial Libraries via Hybrid Data Mining Methods

Characterization and in vitro degradation of poly(octadecanoic anhydride)

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