Mathematical modeling of drug release from hydrogel matrices via a diffusion coupled with desorption mechanism

Singh, Manish Pratap; Lumpkin, Janice A.; Rosenblatt, Joel

doi:10.1016/0168-3659(94)90221-6

Cited by 56 publications

(29 citation statements)

References 13 publications

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“…On the contrary, arterial dynamics of heparin, paclitaxel and rapamycin are all characterized by large Damköhler numbers ( Fig. 1), implying that binding is diffusion limited (15,22) and that concentrations of bound and free drug coexist in a quasi-equilibrium so that (6) where equilibrium dissociation constant is determined by ratio of dissociation and association rate constants,…”

Section: Model Reductionmentioning

confidence: 99%

Diffusion‐limited binding explains binary dose response for local arterial and tumour drug delivery

Tzafriri¹,

Levin²,

Edelman³

2009

Cell Proliferation

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Background Local drug delivery has transformed medicine, yet it remains unclear how drug efficacy depends on physicochemical properties and delivery kinetics. Most therapies seek to prolong release, yet, recent studies demonstrate sustained clinical benefit following local bolus endovascular delivery. Objectives The purpose of the current study was to examine the interplay between drug dose, diffusion and binding in determining tissue penetration and effect. Methods We introduce a quantitative framework that balances dose, saturable binding and diffusion and measured the specific binding parameters of drugs to target tissues. Results Model reduction techniques augmented by numerical simulations revealed that the impact of saturable binding on drug transport and retention is determined by the magnitude of a binding potential, Bp, the ratio of the binding capacity to the product of the equilibrium dissociation constant and accessible tissue volume fraction. At low Bp (<1) drugs are predominantly free and transport scales linearly with concentration. At high Bp (>40) drug transport exhibits a threshold dependence on applied surface concentration. Conclusions In this paradigm, drugs and antibodies with large Bp penetrate faster and deeper into tissues when presented at high concentrations. A threshold dependence of tissue transport on the applied surface concentration of paclitaxel and rapamycin may explain the threshold dose dependence of the in vivo biological efficacy of these drugs.

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Section: Model Reductionmentioning

confidence: 99%

Diffusion‐limited binding explains binary dose response for local arterial and tumour drug delivery

Tzafriri¹,

Levin²,

Edelman³

2009

Cell Proliferation

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“…7(A) and 8(A) for details]. This excellent antimicrobial durability is most likely attributable to the disassociation coupled with diffusion release mechanism41 of the new system, as described earlier.…”

Section: Resultsmentioning

confidence: 78%

“…Therefore, the amount of bound drug will be much higher than the amount of free drug. This coupled disassociation and diffusion release mechanism41 may be the major reason for the sustained drug release of the new system, which can lead to relatively long antimicrobial durations.…”

Section: Resultsmentioning

confidence: 99%

Chitosan‐based rechargeable long‐term antimicrobial and biofilm‐controlling systems

Cao¹,

Sun²

2008

J Biomedical Materials Res

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Chitosan, a natural cationic polymer, strongly binds anionic antibiotics (e.g., rifampin) through the formation of ionic complexes. The new system shows sustained rifampin release, leading to potent antimicrobial and biofilm-controlling functions against gram-positive bacteria including Staphylococcus epidermidis and Staphylococcus aureus, which are responsible for a wide range of medical device-related infections, for longer than 30 days. Moreover, the released drugs can be recharged to further extend antimicrobial durations. Drug release mechanisms and potential applications of the new system are also discussed.

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“…Mathematical modeling can be used to provide valuable insights into the effect of hydrogel properties on bioactive release due to degradation processes [149].…”

Section: Modeling Releasementioning

confidence: 99%

Designing hydrogel particles for controlled or targeted release of lipophilic bioactive agents in the gastrointestinal tract

Zhang

Chen

et al. 2015

European Polymer Journal

160

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Mathematical modeling of drug release from hydrogel matrices via a diffusion coupled with desorption mechanism

Cited by 56 publications

References 13 publications

Diffusion‐limited binding explains binary dose response for local arterial and tumour drug delivery

Diffusion‐limited binding explains binary dose response for local arterial and tumour drug delivery

Chitosan‐based rechargeable long‐term antimicrobial and biofilm‐controlling systems

Designing hydrogel particles for controlled or targeted release of lipophilic bioactive agents in the gastrointestinal tract

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