Modelling receptor-mediated endocytosis in hollow microneedle-based verapamil delivery through viscoelastic skin DOI

Tanmoy Bhuimali,

Sarifuddin Sarifuddin,

Prashanta Kumar Mandal

и другие.

Computer Methods in Biomechanics & Biomedical Engineering, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Март 20, 2025

Drug delivered from the microneedle (MN) tip diffuses across viscoelastic skin before entering blood compartment and being absorbed. Reversible uptake kinetics between tissue compartments, reversible specific saturable binding with its receptors, endocytosis are given due attention. Simulations predict that, unlike thinning, viscoelasticity a higher Young's modulus value, as in an older person, inhibit verapamil diffusion within skin, metabolism stabilises concentrations compartments. Simultaneously, irreversible improve drug compartment, facilitating receptor-mediated endocytosis. The results also that internalised increases time at slower internalisation rates; however, rates, it attains peak value gradually diminishing. Furthermore, rate of lysosomal degradation escalates, concentration diminishes shifts upward. A comprehensive sensitivity analysis has been performed because uncertainty about several crucial parameters. Our findings align well existing literature.

Язык: Английский

Modelling Hollow Microneedle-Mediated Drug Delivery in Skin Considering Drug Binding DOI Creative Commons

Tanmoy Bhuimali,

Sarifuddin Sarifuddin,

Diganta Bhusan Das

и другие.

Pharmaceutics, Год журнала: 2025, Номер 17(1), С. 105 - 105

Опубликована: Янв. 14, 2025

Background/Objectives: Microneedle(MN)-based drug delivery is one of the potential approaches to overcome limitations oral and hypodermic needle delivery. An in silico model has been developed for hollow microneedle (HMN)-based skin its subsequent absorption blood tissue compartments presence interstitial flow. The drug’s reversible specific saturable binding receptors kinetics across have taken into account. Methods: governing equations representing flow fluid, transport verapamil viable concentrations are solved using combined Marker Cell Immersed Boundary Methods gain a quantitative understanding under consideration. Results: viscoelastic predicted impede and, hence, reduce all forms compartments. findings reveal that higher mean concentration not always associated with longer MN length. Simulations also predict bound compartment rise decreasing tip diameters. In contrast, free increases increasing injection velocities. Conclusions: novelty this study includes metabolism two-dimensional irregular nonlinear, specific, saturable, compartment. diameter velocity thought serve as regulatory parameters effectiveness efficacy MN-mediated therapy if robust enough sustain force needed penetrate wider skin.

Язык: Английский

Процитировано

2

Modelling receptor-mediated endocytosis in hollow microneedle-based verapamil delivery through viscoelastic skin DOI

Tanmoy Bhuimali,

Sarifuddin Sarifuddin,

Prashanta Kumar Mandal

и другие.

Computer Methods in Biomechanics & Biomedical Engineering, Год журнала: 2025, Номер unknown, С. 1 - 19

Опубликована: Март 20, 2025

Drug delivered from the microneedle (MN) tip diffuses across viscoelastic skin before entering blood compartment and being absorbed. Reversible uptake kinetics between tissue compartments, reversible specific saturable binding with its receptors, endocytosis are given due attention. Simulations predict that, unlike thinning, viscoelasticity a higher Young's modulus value, as in an older person, inhibit verapamil diffusion within skin, metabolism stabilises concentrations compartments. Simultaneously, irreversible improve drug compartment, facilitating receptor-mediated endocytosis. The results also that internalised increases time at slower internalisation rates; however, rates, it attains peak value gradually diminishing. Furthermore, rate of lysosomal degradation escalates, concentration diminishes shifts upward. A comprehensive sensitivity analysis has been performed because uncertainty about several crucial parameters. Our findings align well existing literature.

Язык: Английский

Процитировано

0