Mesoscopic Simulation for the Effect of Cross-Linking Reactions on the Drug Diffusion Properties in Microneedles

Abstract

The drug diffusion issue in microneedles is the focus of its medical application. It will not only affect the distribution of drugs in the needle body but will also have an impact on the drug release performance of the microneedle. The utilization of cross-linked polymer materials to obtain the drug diffusion control has been experimentally verified as a feasible method. However, the mechanism research on the molecular level is still incomplete. In this study, the dissipative particle dynamics (DPD) simulation has been applied to study the effect of the crosslinking reaction on drug diffusion in hyaluronic acid microneedles. We have discovered that when the cross-linking degree reaches 90%, the diffusion coefficient of the drug is 6.45 times lower than that of the uncross-linked system. The main reason for the decline in drug diffusion ability is that the cross-linking reaction varies the conformation of the polymer. The amplification in the cross-linking degree makes the polymer coils more compact and approach each other, finally forming a continuously distributed cross-linked network, which reduces its degradation rate in the body. Simultaneously, these cross-linked networks can also hinder the interaction of soluble drugs with water, thereby preventing the premature release of drugs. The simulation results are consistent with the data collected in the previous microneedle experiment. This work will be an extension of DPD simulation in the application of biological materials. HIGHLIGHT FOR REVIEWERS• Cross-linking reaction model is established in the DPD simulation for microneedle research. • The cross-linking reaction inhibits the diffusion of the drug by hindering the interaction between the drug and the water molecules. • The amplification in the cross-linking degree leads to a continuously distributed cross-linked network. • The simulation results are consistent with the data collected in the previous microneedle experiment.

Morphological transitions of micelles induced by the block arrangements of copolymer blocks: dissipative particle dynamics simulation

“…The density distribution and the radius of gyration ( R g ) were widely employed in the study of morphological and structural characterization of copolymer micelles, 37 as described in detail in the ESI †…”

Self-Nanoformulating Poly(2-oxazoline) and Poly(2-oxazine) Copolymers Based Amorphous Solid Dispersions as Microneedle Patch: A Formulation Study

“…This rapid release phenomenon is consistent with existing literature, [34,37] which suggests that lower drug-to-polymer ratios typically yield matrices with less physical cross-linking, and, thus, a looser network structure that permits a faster dissolution of the amorphous solid dispersion into micelles. [45,46] This could be particularly advantageous in clinical scenarios necessitating a quick onset of action. However, the trade-off is a shorter duration of therapeutic effect, which may not be ideal for conditions requiring prolonged drug exposure.…”

Application of hydrogel microneedles in the oral cavity

“…HA Biocompatible; non-immunogenic; dissolving; easily acquired; fast drug release Weak mechanical properties Burst releasing of loaded drug [139] HAMA Controlled drug release; better mechanical property; photocurable Sustained drug releasing [140] GelMa Photocurable; biodegradable; can promote cell attachment and remodeling; adjustable mechanical properties Weak mechanical properties Used to promote wound healing and delivery active substance [141] Chitosan Biocompatible; antibacterial; rich functionality and modifiability; polycationic; biodegradable; antiinflammatory Water-insoluble; the low molecular weight polymer has poor mechanical strength Used to promote wound healing [15] PVA improve drug stability and be processed into nanoparticles [142] PVP More significant impact on enhancing the dissolution rate; biocompatibility; ability to enhance drug solubility and permeability; fast drug release Used to achieve the graded release of drugs [68] T A B L E 3 Current application and future possibilities of hydrogel microneedles in the oral cavity.…”