Microfluidic Assembly of Monodisperse Multistage pH‐Responsive Polymer/Porous Silicon Composites for Precisely Controlled Multi‐Drug Delivery

Abstract

We report an advanced drug delivery platform for combination chemotherapy by concurrently incorporating two different drugs into microcompoistes with ratiometric control over the loading degree. Atorvastatin and celecoxib were selected as model drugs due to their different physicochemical properties and synergetic effect on colorectal cancer prevention and inhibition. To be effective in colorectal cancer prevention and inhibition, the produced microcomposite contained hypromellose acetate succinate, which is insoluble in acidic conditions but highly dissolving at neutral or alkaline pH conditions. Taking advantage of the large pore volume of porous silicon (PSi), atorvastatin was firstly loaded into the PSi matrix, and then encapsulated into the pH-responsive polymer microparticles containing celecoxib by microfluidics in order to obtain multi-drug loaded polymer/PSi microcomposites. The prepared microcomposites showed monodisperse size distribution, multistage pH-response, precise ratiometric controlled loading degree towards the simultaneously loaded drug molecules, and tailored release kinetics of the loaded cargos. This attractive microcomposite platform protects the payloads from being released at low pH-values, and enhances their release at higher pH-values, which can be further used for colon cancer prevention and treatment. Overall, the pH-responsive polymer/PSi-based microcomposite can be used as a universal platform for the delivery of different drug molecules for combination therapy.

Microfluidic assisted one-step fabrication of porous silicon@acetalated dextran nanocomposites for precisely controlled combination chemotherapy

“…The additional benefit of this approach is that the loading degree of hydrophilic therapeutics can be significantly enhanced in comparison with the traditional solid carriers, because of the prominent high loading degree of PSi materials for hydrophilic therapeutics [15]. Therefore, the composites formed by embedding the PSi particles within solid carrier matrices combine the advantages of both materials and facilitate the ratio drug delivery control over different therapeutics [16]. However, these studies were limited to the microfluidic assembled microcomposites, and the high efficient enveloping of a PSi nanoparticle inside a solid nanoparticle matrix on a 1:1 ratio still remains a challenge.…”

Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs

“…The SEM images also showed a homogeneous size distribution, suggesting the production of monodisperse particles by the microfluidic technique. 11 The DPP4 inhibitor encapsulation efficiency was 20 ± 5 %. Considering the amount (mass) of DPP4 inhibitor in the final formulation and that the IC 50 of the DPP4 inhibitor is of 14 nM, the amount of inhibitor present in the current formulation should be more than enough to be active and to inhibit the enzyme activity efficiently.…”

“…9 On the other hand PSi nanoparticles have large surface area, pore volumes with adjustable diameters (2-50 nm), as well as higher drug loading capacity compared to the majority of the other materials. [10][11][12] Furthermore, the drug loading is usually a simple process where the drug is retained inside the mesopores by physical adsorption or electrostatic interactions. 10 Nevertheless, the oral delivery of PLGA and PSi nanoparticles is not in such advanced state.…”

Targeting thyroid cancer with acid-triggered release of doxorubicin from silicon dioxide nanoparticles

“…Acid-responsive drug delivery would be beneficial for cancer therapy due to the acidic tumor microenvironment. [27][28][29][30] To show the acid-triggered release of Dox from the NPs, TSH-SiO 2 @Dox-NPs were put into dialysis bags (molecular weight cut-off 3,500 Da) and then incubated in acetate-buffered solution (pH =5.0) and phosphate-buffered solution (PBS; pH =7.4), respectively. These two pH values at 5.0 and 7.4 could simulate the pH values in the blood circulation 31 and within tumor cells.…”