Matrix Density Engineering of Hydrogel Nanoparticles with Simulation-Guided Synthesis for Tuning Drug Release and Cellular Uptake

Abstract

The use of a nanoparticle (NP)-based antitumor drug carrier has been an emerging strategy for selectively delivering the drugs to the tumor area and, thus, reducing the side effects that are associated with a high systemic dose of antitumor drugs. Precise control of drug loading and release is critical so as to maximize the therapeutic index of the NPs. Here, we propose a simple method of synthesizing NPs with tunable drug release while maintaining their loading ability, by varying the polymer matrix density of amine- or carboxyl-functionalized hydrogel NPs. We find that the NPs with a loose matrix released more cisplatin, with up to a 33 times faster rate. Also, carboxyl-functionalized NPs loaded more cisplatin and released it at a faster rate than amine-functionalized NPs. We performed detailed Monte Carlo computer simulations that elucidate the relation between the matrix density and drug release kinetics. We found good agreement between the simulation model and the experimental results for drug release as a function of time. Also, we compared the cellular uptake between amine-functionalized NPs and carboxyl-functionalized NPs, as a higher cellular uptake of NPs leads to improved cisplatin delivery. The amine-functionalized NPs can deliver 3.5 times more cisplatin into cells than the carboxyl-functionalized NPs. The cytotoxic efficacy of both the amine-functionalized NPs and the carboxyl-functionalized NPs showed a strong correlation with the cisplatin release profile, and the latter showed a strong correlation with the NP matrix density.

Bioactive hydrogels for bone regeneration

“…Ideal hydrogels, due to their unique structure, can also release bioactive factors in a spatiotemporally controlled manner and maintain a sustained release to allow for continuous formation of bone matrix and vascular network [ 92 ]. The molecular diffusion and hydrogel degradation rate are the main influencing factors that can be modulated via alteration of the structure and concentrations of polymers and crosslinkers [ 1 ].…”

Untitled

“…The utilization of synthetic biomaterials is a potential alternative to the use of autografts and allografts. In cases where osteonecrosis attacks larger areas such as joints, the total joint substitute method must take place [123][124][125][126][127]. Recently, there are several types of research are ongoing through all appropriate fields, and it is expected that many bone diseases method secondary to trauma, bone resection due to subtractive surgery, aging, and metabolic or genetic skeletal disorders will be successfully treated with novel bone-regeneration protocols that may address both local and systemic embellishment to optimize outcome.…”

Hydrogel-Based Drug Delivery Nanosystems for the Treatment of Brain Tumors

“…In a different perspective, Shirakura et al [104] resort to MC simulations to inspect the relation between the matrix density of hydrogel nanoparticles and the kinetics of drug release, by changing the mesh size through variations in the cross-linking. The study was conducted using CIS as a model drug and the authors found a good agreement between the simulation and the experimental results.…”