Nanoparticles for Combination Drug Therapy

Abstract

Nanoparticles have recently emerged as a promising class of carriers for the co-delivery of multiple drugs. Combination therapies of small-molecule drugs are common in clinical practice and it is anticipated that packaging into single macromolecular carriers will enable drug release in precisely balanced ratios and rates, and in selectively targeted tissues and cells. This vast level of pharmacological control is intriguing, especially from the perspective of tailoring personalized treatments with maximized therapeutic synergy for individual patients. Here, we discuss promising formulations and opportunities to employ advanced screening tools and new animal models of disease that can improve chances for successful clinical translation.

Dual Carfilzomib and Doxorubicin–Loaded Liposomal Nanoparticles for Synergistic Efficacy in Multiple Myeloma

“…Although this will not accurately represent MTD for NP [carfþdox], it can still be used to set the dosing parameters for comparison studies, as we expect the nanoparticle formulations to be less toxic relative to the free drug formulations (5,9,12). SCID mice were subcutaneously injected with NCI-H929 cells.…”

“…Although two drugs can demonstrate synergy, they are usually only synergistic, or exhibit the greatest synergy, at specific drug-to-drug molar ratios (2)(3)(4). Although the two drugs may be administered at the optimal drug ratio for synergy, this does not ensure that this ratio will be maintained at the tumor site due to differences in injection schedules, pharmacokinetic properties, metabolism, and nonuniform biodistribution (5)(6)(7). In order for combination therapies to achieve maximal antitumor effects and improved patient outcomes, it is imperative that the drugs reach the tumor at their optimal molar ratio.…”

Natural material-decorated mesoporous silica nanoparticle container for multifunctional membrane-controlled targeted drug delivery

“…Cell viability was calculated using the formula: % viability = A s / A c , where A s and A c are the absorbance of the treated and untreated samples, respectively. The same method was used to determine the cytotoxicity of free DOX and DOX-loaded nanoparticles (DOX@MSN, DOX@MSN-NH 2 …”

“…1 An ideal drug delivery system accurately releases the drug at a precise time and location, thereby reducing the possibility of premature or off-target effects. 2 Despite recent advances in nanoparticle drug delivery systems, achieving an optimal therapeutic effect remains a significant challenge. [3][4][5] An advantage of nanoparticle carriers such as mesoporous silica nanoparticles (MSNs), [6][7][8][9][10][11][12] liposomes, [13][14][15] and carbon nanotubes, 16 which are usually considered to be the drug storage "warehouse" for drug delivery, is their high drug-loading (DL) capacity.…”

Enzymatically degradable hybrid organic–inorganic bridged silsesquioxane nanoparticles for in vitro imaging

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14] The nanoscale dimension of such materials endows them with long blood circulation times as well as preferential accumulation in cancerous tissues with the so-called enhanced permeation and retention effect. 15,16 However, one of the crucial challenges to be addressed for their future applications is the ability to degrade in biological environment.…”