Solute diffusion in genetically engineered silk–elastinlike protein polymer hydrogels

Dinerman, Adam A.; Cappello, Joseph; Ghandehari, Hamidreza; Hoag, Stephen W.

doi:10.1016/s0168-3659(02)00134-7

Cited by 84 publications

(69 citation statements)

References 17 publications

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“…[36][37][38][39][40] Four types of antibody and antibody fragments with different molecular weights (MWs) were chosen to study the influence of the reagent size on the release. The radii of the antibodies were calculated using nm 0.066 Da…”

Section: Influence Of Reagent Size On the Releasementioning

confidence: 99%

Controlled antibody release from gelatin for on-chip sample preparation

Zhang¹,

Wasserberg²,

Breukers³

et al. 2016

Analyst

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A practical way to realize on-chip sample preparation for point-of-care diagnostics is to store the required reagents on a microfluidic device and release them in a controlled manner upon contact with the sample. For the development of such diagnostic devices, a fundamental understanding of the release kinetics of reagents from suitable materials in microfluidic chips is therefore essential. Here, we study the release kinetics of fluorophore-conjugated antibodies from (sub-) µm thick gelatin layers and several ways to control the release time. The observed antibody release is well-described by a diffusion model. Release times ranging from ~20 s to ~650 s were determined for layers with thicknesses (in the dry state) between 0.25 µm and 1.5 µm, corresponding to a diffusivity of 0.65 µm 2 /s (in the swollen state) for our standard layer preparation conditions. By modifying the preparation conditions, we can influence the properties of gelatin to realize faster or slower release. Faster drying at increased temperatures leads to shorter release times, whereas slower drying at increased humidity yields slower release. As expected in a diffusive process, the release time increases with the size of the antibody. Moreover, the ionic strength of the release medium has a significant impact on the release kinetics. Applying these findings to cell counting chambers with on-chip sample preparation, we can tune the release to control the antibody distribution after inflow of blood in order to achieve homogeneous cell staining. IntroductionOne of the major fields of applications for microfluidics is in vitro diagnostics, with great potential particularly in point-of-care diagnostics. 1-3 Many process steps and sensing principles have been realized on microfluidic devices. 4 Recently, on-chip sample preparation using reagents stored in microfluidic devices has received more and more attention. 5 On-chip sample preparation can eliminate the dependence on external instrumentation for reagent delivery as well as benchtop sample treatment, thus integrating the complete test into one disposable. 6 To realize on-chip sample preparation, reagents are integrated in microfluidic devices and released upon contact with the inflowing sample. Compared with liquid reagents 7-10 , integrating dry reagents in microfluidic devices is beneficial for long-term storage and convenient for transportation, due to the better stability of reagents in the dry state. 11 However, the controlled dissolution of the reagent and on-chip mixing with the added sample is challenging. Especially in applications where the inflowing sample passes a reservoir of the reagent and slowly dissolves or washes out the stored reagent 12-15 , very precise control of the sample flow and the reagent release process is required. In contrast, mixing between sample and reagents in stopped flow applications can be realized simply by releasing the reagent with sufficient delay after the sample inflow has stopped at the required position on the chip. 16 To realize controlled reagen...

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Section: Influence Of Reagent Size On the Releasementioning

confidence: 99%

Controlled antibody release from gelatin for on-chip sample preparation

Zhang¹,

Wasserberg²,

Breukers³

et al. 2016

Analyst

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“…22 A decrease in cross-linking density can result in an increase in the degree of swelling. An increase in molecular weight of the polymer chains can result in an q 10 increase in inter-and intrapolymer interactions and entangle-I ft ments, leading to increased cross-linking density and decreased degree of swelling and drug/gene release.…”

Section: Imentioning

confidence: 99%

“…The kinetics of this sol-to-gel transition allow solutions of polymer and bioactive agents with aqueous solubility to be prepared at room temperature and injected through a small gauge needle, with hydrogel matrices formed in situ within minutes. The hydrogels release the incorporated bioactive agents through diffusion and/or matrix degradation (22,23). While the applications of SELP-mediated controlled gene delivery are numerous, we have focused our efforts on the controlled delivery of plasmid DNA and adenoviral vectors to solid tumors.…”

Section: Amount Of Non-freezable Water In Selp-47k Hydrogelsmentioning

confidence: 99%

“…A number of classes of recombinant polymers have now been synthesized, including the elastin-like polymers (ELPs) (15,16), silk-like polymers (SLPs) (17,18), silk-elastinlike polymers (SELPs) (13,19), poly(glutamic acid)s (20), silk-collagen polymers (14), and others (21). Several of these polymers have been characterized for biomedical applications including controlled release (22,23), tissue repair (24), and targeted drug delivery (25). In our laboratory, we use genetically engineered protein polymers both as a research tool, to understand structure/property relationships, and as a therapeutic tool, to deliver DNA to solid tumors.…”

Section: Introductionmentioning

confidence: 99%

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Silk-Elastinlike Copolymers for Breast Cancer Gene Therapy

Ghandehari¹

2005

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Public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering end maintaining the data needed, and completing and reviewing this collection of information. Send comments regarding this burden estimate or any other aspect of this collection of information, including suggestions for reducing this burden to Washington Headquarters Services, Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302, and to the Office of Management and Budget, AUTHOR(S)Hamid Ghandehari, Ph.D. PERFORMING ORGANIZA TION NAME(S) AND ADDRESS(ESJ ABSTRACT (Maximum 200 Words)The overall purpose of the project is to use silkelastin-like polymers (SELPs) for the development of controlled gene delivery systems for localized breast cancer gene therapy. The rationale is that by controlling the structure of the polymer, it is possible to control DNA release, duration of transgene expression and the corresponding reduction in tumor size. In year 2 progress was made in the following areas: i) Finished the biosynthesis of three SELP 415K analogs with incremental increase in molecular weight and started on the biosynthesis of SELP 815K, ii) Compared the physicochemical characteristics of hydrogels made from SELP 415K and SELP 47K, iii) Compared the DNA release characteristics of hydrogels made from SELP 415K and SELP 47K and evaluated the interaction of DNA with these polymers. The next logical steps are to finish the biosynthesis of the third analog (815K), conduct characterization and release studies using hydrogels made from this analog and evaluate the delivery systems in murine models of breast cancer as proposed in the application. University of Maryland, Baltimore INTRODUCTION:The overall purpose of the project is to use silkelastin-like polymers (SELPs) for the development of controlled gene delivery systems for localized breast cancer gene therapy. The rationale is that by controlling the structure of the polymer, it is possible to control DNA release, duration of transgene expression and the corresponding reduction in tumor size. Three Specific Aims were proposed: 1) To synthesize and characterize a series of SELP hydrogels.2) To examine the influence of polymer structure on DNA release in vitro.3) To evaluate the influence of polymer structure on transfection efficiency and therapeutic efficacy in vivo.In year 2 of the project progress was made to partially accomplish Aims 1 and 2. In addition related areas were explored as outlined in the body of this report. Factors that influence hydrogel properties are not only polymeric structure (as proposed in the grant application) but also polymeric molecular weight. The biosynthesis of the additional analogs will allow us to establish the relationship between polymer molecular weight on one hand with hydrogel properties, DNA release, and in vivo transfection efficiency on the other. 1Annual Report (Apr...

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“…103 However, the release from these matrices is rapid, occurring almost completely in a matter of h, even for large protein drugs. 104 In Situ Cross-Linking Hydrogels Hydrogels can be formed from liquid or soluble precursors by in situ chemical reaction by a number of mechanisms including thermal polymerization, photopolymerization, or in situ polymer-polymer cross-linking reactions. For any application, it is desirable for such reactions to take place under biologically compatible conditions and usually with minimal side reactions to nearby tissue.…”

mentioning

confidence: 99%

Injectable hydrogels

Overstreet

Dutta

Stabenfeldt

et al. 2012

J Polym Sci B Polym Phys

163

124

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Hydrogels are promising for a variety of medical applications due to their high water content and mechanical similarity to natural tissues. When made injectable, hydrogels can reduce the invasiveness of application, which in turn reduces surgical and recovery costs. Key schemes used to make hydrogels injectable include in situ formation due to physical and/or chemical cross-linking. Advances in polymer science have provided new injectable hydrogels for applications in drug delivery and tissue engineering. A number of these injectable hydrogel systems have reached the clinic and impact the health care of many patients. However, a significant remaining challenge is translating the ever-growing family of injectable hydrogels developed in laboratories around the world to the clinic. V C 2012 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 50: 2012

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Solute diffusion in genetically engineered silk–elastinlike protein polymer hydrogels

Cited by 84 publications

References 17 publications

Controlled antibody release from gelatin for on-chip sample preparation

Controlled antibody release from gelatin for on-chip sample preparation

Silk-Elastinlike Copolymers for Breast Cancer Gene Therapy

Injectable hydrogels

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