Modeling of small-molecule release from crosslinked hydrogel microspheres: Effect of crosslinking and enzymatic degradation of hydrogel matrix

Cheng, Felice; Choy, Young Bin; Choi, Hyungsoo; Kim, Kyekyoon Kevin

doi:10.1016/j.ijpharm.2010.10.029

Cited by 14 publications

(6 citation statements)

References 27 publications

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“…As Lao et al reported, when both diffusion and reaction phenomena are occurring within a biodegradable polymer, drug release can be modeled by a three-step sequence: solvent penetration, degradation-dependent relaxation, and drug diffusion . Cheng et al have also applied this multistep approach to model degradation and diffusion from enzymatically degradable gelatin. Although surface and bulk degradation likely occur simultaneously, Himmelstein and co-workers , modeled the simultaneous diffusion-reaction transport due to acid-catalyzed hydrolysis and used the ratio of characteristic times of diffusion and reaction, shown in eq , to predict the type of degradation. When the ratio is greater than unity, the degradation is limited by diffusion and surface erosion is more likely to occur.…”

Section: Resultsmentioning

confidence: 99%

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Enzymatic Biodegradation of Hydrogels for Protein Delivery Targeted to the Small Intestine

2015

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Multiresponsive poly(methacrylic acid-co-N-vinylpyrrolidone) hydrogels were synthesized with biodegradable oligopeptide crosslinks. The oligopeptide crosslinks were incorporated using EDC-NHS zero-length links between the carboxylic acid groups of the polymer and free primary amines on the peptide. The reaction of the peptide was confirmed by primary amine assay and IR spectroscopy. The microgels exhibited pH-responsive swelling as well as enzyme-catalyzed degradation targeted by trypsin present in the small intestine, as demonstrated upon incubation with gastrointestinal fluids from rats. Relative turbidity was used to evaluate enzyme-catalyzed degradation as a function of time, and initial trypsin concentration controlled both the degradation mechanism as well as the extent of degradation. Trypsin activity was effectively extinguished by incubation at 70 °C, and both the microgels and degradation products posed no cytotoxic effect toward two different cell lines. The microgels demonstrated pH-dependent loading of the protein insulin for oral delivery to the small intestine.

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Section: Resultsmentioning

confidence: 99%

“…Cheng et al 52 have also applied this multi-step 27,54 modeled the simultaneous diffusion-reaction transport due to acid-catalyzed hydrolysis and used the ratio of characteristic times of diffusion and reaction, shown in Eq. 7, to predict the type of degradation.…”

Section: Degradationmentioning

confidence: 99%

Enzymatic Biodegradation of Hydrogels for Protein Delivery Targeted to the Small Intestine

2015

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“…In addition, Trypan blue has been used as a common model for charged drug species in hydrogel diffusion and controlled release studies. [54][55][56][57][58] Recently, it has even been used to analyze cell viability via perfusion through hydrogels into the bulk tissue of the brain-on-chip model. 59 Due to its diffusion properties, broad use as a model drug and high extinction coefficient which enables the easy imaging of diffusion gradients, we selected Trypan blue as the model solute to characterize diffusion from the perfused media, across the microvessel wall and into the cell culture chamber (Figure 3).…”

Section: Empirical Diffusion Measurements In Manifold Devicementioning

confidence: 99%

Microvessel manifold for perfusion and media exchange in three-dimensional cell cultures

et al. 2016

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Integrating a perfusable microvasculature system is a substantial challenge for "on-chip" tissue models. We have developed an inclusive on-chip platform that is capable of maintaining laminar flow through porous biosynthetic microvessels. The biomimetic microfluidic device is able to deliver and generate a steady perfusion of media containing small-molecule nutrients, drugs, and gases in three-dimensional cell cultures, while replicating flow-induced mechanical stimuli. Here, we characterize the diffusion of small molecules from the perfusate, across the microvessel wall, and into the matrix of a 3D cell culture.

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“…The success of these formulations, (i.e., gelatin, hydrogel, and scaffolds) was enhanced by cross-linking agents such as glutaraldehyde, sugar, and enzyme transglutaminase. It was also discovered that the cross-linking density of gelatin was able to affect the rate of degradation and rate of bioactive agents release from gelatin vehicles or from liposomes embedded inside gelatin-based systems [127–130]. Another study by Peptu and coworkers [83] reported a controlled release of liposome-encapsulated calcein fluoroscence dye or calcein labeled with rhodamine from temporary depot of gelatin-based system which is made up of Gelatin-carboxymethylcellulose films.…”

Section: Natural Product-based Liposomal Drug Delivery Systemsmentioning

confidence: 99%

A Review on Composite Liposomal Technologies for Specialized Drug Delivery

Mufamadi

Pillay

Choonara

et al. 2011

Journal of Drug Delivery

200

132

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The combination of liposomes with polymeric scaffolds could revolutionize the current state of drug delivery technology. Although liposomes have been extensively studied as a promising drug delivery model for bioactive compounds, there still remain major drawbacks for widespread pharmaceutical application. Two approaches for overcoming the factors related to the suboptimal efficacy of liposomes in drug delivery have been suggested. The first entails modifying the liposome surface with functional moieties, while the second involves integration of pre-encapsulated drug-loaded liposomes within depot polymeric scaffolds. This attempts to provide ingenious solutions to the limitations of conventional liposomes such as short plasma half-lives, toxicity, stability, and poor control of drug release over prolonged periods. This review delineates the key advances in composite technologies that merge the concepts of depot polymeric scaffolds with liposome technology to overcome the limitations of conventional liposomes for pharmaceutical applications.

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Modeling of small-molecule release from crosslinked hydrogel microspheres: Effect of crosslinking and enzymatic degradation of hydrogel matrix

Cited by 14 publications

References 27 publications

Enzymatic Biodegradation of Hydrogels for Protein Delivery Targeted to the Small Intestine

Enzymatic Biodegradation of Hydrogels for Protein Delivery Targeted to the Small Intestine

Microvessel manifold for perfusion and media exchange in three-dimensional cell cultures

A Review on Composite Liposomal Technologies for Specialized Drug Delivery

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