Mechanistic relationships between polymer microstructure and drug release kinetics in bioerodible polyanhydrides

Shen, Elizabeth; Kipper, Matt J.; Dziadul, Brianne; Lim, Mee-Kyung; Narasimhan, Balaji

doi:10.1016/s0168-3659(02)00125-6

Cited by 114 publications

(183 citation statements)

References 22 publications

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“…The maximal graft density ρ g,max is ≈ 1nm −2 as calculated from the estimated specific surface area of MMT, 600 m 2 g , 88 and ion exchange capacity of 0.92 meq g . ATRP reactions were conducted using unbound EBP or BBr as the initiator using molar ratios of monomer, initiator, Cu I Br, Cu II Br 2 , and PMDETA equal to 1000:1:1:0.06:1.06.…”

Section: Resultsmentioning

confidence: 98%

“…Montmorillonite clay was generously supplied by Southern Clay Products Inc. Based on the ion exchange capacity, 92 mequiv 100g , and measurements of the specific surface area, 139 MMT contains ≈ 1 site nm 2 . Functionalized MMT (fMMT) was prepared via ion exchange of pristine MMT with a bromine terminated alkylammonium surfactant.…”

Section: Methodsmentioning

confidence: 99%

“…The benefits of CPAs arise from the interaction of the drug with the encapsulating polymer in terms of polymer microstructure, compatibility of the drug with the polymer, and solubility of the drug in the polymer. 170 The intelligent design of drug delievery devices for biomedical applications necessitates a detailed understanding of the drug interactions with the host polymer as well as the release mechanism of the delivery device. This is especially true for biodegradable polymers where the diffusion of drugs through the polymer, the polymer degradation rate, and diffusion of degraded monomer away from the bulk surface all play key roles in determining drug release rates.…”

Section: Applications Of Cpasmentioning

confidence: 99%

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Hierarchically Ordered Montmorillonite Block Copolymer Brushes

2010

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Section: Resultsmentioning

confidence: 98%

Section: Methodsmentioning

confidence: 99%

Section: Applications Of Cpasmentioning

confidence: 99%

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Hierarchically Ordered Montmorillonite Block Copolymer Brushes

2010

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“…Here, L CPH is the number average sequence length of CPH in the copolymer reported by Shen et al 38 and k CPH-SA is the rate constant for the degradation of CPH-SA bonds, approximated here as k SA-SA . The rate constant for degradation of SA-SA bonds is approximated as 2k SA .…”

Section: Model Solution For Poly(cph:sa) 20:80mentioning

confidence: 99%

Molecular Description of Erosion Phenomena in Biodegradable Polymers

Kipper

Narasimhan

2005

Macromolecules

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A new model for the erosion kinetics of semicrystalline surface-erodible homopolymers and copolymers is presented. The model is derived for a class of surface-erodible polyanhydride copolymers, with the goal of describing erosion in terms of fundamental, elementary processes. This model is based on an accurate description of copolymer microstructure and can thereby account for the heterogeneous erosion due to microphase separation and crystallinity. In addition to accurately predicting the overall erosion profile and the release of individual monomer species, several key phenomena that occur during erosion are described. These include precipitation of slightly soluble degradation products inside the pores of the erosion zone and pH changes during erosion due to dissolution of acidic monomers and the consequent changes in monomer solubility. This model also motivates future experiments to investigate predicted phenomena such as the effects due to local changes in pH and degradation rate constants for crystalline and amorphous moieties. The rational design of biomedical devices such as vehicles for drug delivery and scaffolds for tissue engineering will be aided by the application of this model and future extensions of it. Received November 13, 2004; Revised Manuscript Received December 13, 2004 ABSTRACT: A new model for the erosion kinetics of semicrystalline surface-erodible homopolymers and copolymers is presented. The model is derived for a class of surface-erodible polyanhydride copolymers, with the goal of describing erosion in terms of fundamental, elementary processes. This model is based on an accurate description of copolymer microstructure and can thereby account for the heterogeneous erosion due to microphase separation and crystallinity. In addition to accurately predicting the overall erosion profile and the release of individual monomer species, several key phenomena that occur during erosion are described. These include precipitation of slightly soluble degradation products inside the pores of the erosion zone and pH changes during erosion due to dissolution of acidic monomers and the consequent changes in monomer solubility. This model also motivates future experiments to investigate predicted phenomena such as the effects due to local changes in pH and degradation rate constants for crystalline and amorphous moieties. The rational design of biomedical devices such as vehicles for drug delivery and scaffolds for tissue engineering will be aided by the application of this model and future extensions of it.

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“…For instance, factors that influence polymer degradation, drug release kinetics, and stability are the polymer degradation rate (controlled by the polymer chemistry), the drug loading, and polymer-drug interactions. 4,5,8 Therefore, rapid, highthroughput methods that generate and screen compositional libraries of polyanhydride copolymers may be useful in rapidly developing new materials for controlled release applications.…”

Section: Introductionmentioning

confidence: 99%

Parallel Synthesis and High Throughput Dissolution Testing of Biodegradable Polyanhydride Copolymers

et al. 2005

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We have demonstrated that polycondensation reactions can be carried out in a combinatorial fashion and that the polymer library can be screened at high throughput using a rapid prototyping technique to fabricate multiwell substrates. A linearly varying compositional library of 100 different biodegradable polyanhydride random copolymers that are promising carriers for controlled drug delivery was designed, fabricated, and characterized by IR microscopy within a few hours. The polyanhydride copolymer library was based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic anhydride (SA) and was characterized with infrared microspectroscopy to determine the composition within each well. Since degradation and release rates depend on copolymer composition, we also developed new high-throughput methods to investigate drug release from this library of copolymers by designing specific wells for each task. A subset of this library was chosen, and a substrate was designed and fabricated to enable the synthesis and monitoring of dye dissolution from a range of polyanhydride copolymers in a parallel fashion using a CCD camera. Multisample substrates were fabricated with a novel rapid prototyping method that consists of an organic solvent-resistant array of 10 x 10 microwells of 2-Î¼L volume each. The libraries were deposited with a custom-built liquid dispensing system consisting of a series of computer-controlled volume-dispensing pumps and XYZ motion stages. The parallel dye dissolution study displayed a decreasing rate of release with increasing CPH content. This result agrees with previously published data for dye release from poly(CPH-co-SA) copolymers. The methodology described in this work is amenable to numerous applications in the arenas of high-throughput polymer synthesis and characterization. We have demonstrated that polycondensation reactions can be carried out in a combinatorial fashion and that the polymer library can be screened at high throughput using a rapid prototyping technique to fabricate multiwell substrates. A linearly varying compositional library of 100 different biodegradable polyanhydride random copolymers that are promising carriers for controlled drug delivery was designed, fabricated, and characterized by IR microscopy within a few hours. The polyanhydride copolymer library was based on 1,6-bis(p-carboxyphenoxy)hexane (CPH) and sebacic anhydride (SA) and was characterized with infrared microspectroscopy to determine the composition within each well. Since degradation and release rates depend on copolymer composition, we also developed new high-throughput methods to investigate drug release from this library of copolymers by designing specific wells for each task. A subset of this library was chosen, and a substrate was designed and fabricated to enable the synthesis and monitoring of dye dissolution from a range of polyanhydride copolymers in a parallel fashion using a CCD camera. Multisample substrates were fabricated with a novel rapid prototyping method that consists of an organic s...

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Mechanistic relationships between polymer microstructure and drug release kinetics in bioerodible polyanhydrides

Cited by 114 publications

References 22 publications

Hierarchically Ordered Montmorillonite Block Copolymer Brushes

Hierarchically Ordered Montmorillonite Block Copolymer Brushes

Molecular Description of Erosion Phenomena in Biodegradable Polymers

Parallel Synthesis and High Throughput Dissolution Testing of Biodegradable Polyanhydride Copolymers

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