Physiologically Relevant Mechanics of Biodegradable Polyester Nanoparticles

Abstract

Despite the extensive use of biodegradable polyester nanoparticles for drug delivery, and reports of the strong influence of nanoparticle mechanics on nano−bio interactions, there is a lack of systematic studies on the mechanics of these nanoparticles under physiologically relevant conditions. Here, we report indentation experiments on poly­(lactic acid) and poly­(lactide-co-glycolide) nanoparticles using atomic force microscopy. While dried nanoparticles were found to be rigid at room temperature, their elastic modulus was found to decrease by as much as 30 fold under simulated physiological conditions (i.e., in water at 37 °C). Differential scanning calorimetry confirms that this softening can be attributed to the glass transition of the nanoparticles. Using a combination of mechanical and thermoanalytical characterization, the plasticizing effects of miniaturization, molecular weight, and immersion in water were investigated. Collectively, these experiments provide insight for experimentalists exploring the relationship between polymer nanoparticle mechanics and in vivo behavior.

Implications of Quenching‐to‐Dequenching Switch in Quantitative Cell Uptake and Biodistribution of Dye‐Labeled Nanoparticles

“…[22] Temperature also plays ac ritical role in PLGA degradation, and the elastic modulus of PLGA NPs was found to decrease significantly in water at 37 8 8C. [23] The swelling and/or degradation mechanism of PLGA NPs in FBS could also be explained by the adsorption of serum proteins onto the NP surface thus reducing the stability of particles. [24] Thec atalyzing effect of divalent ions (Ca 2+ ,M g 2+ )i nF BS might also accelerate the degradation of PLGA.…”

Oxidative Damage Induced by Phototoxic Pheophorbide a 17-Diethylene Glycol Ester Encapsulated in PLGA Nanoparticles

“…Among a variety of different materials for modern nanodrugs design [ 20 , 21 , 22 ], we chose poly(D,L-lactide-co-glycolide) (PLGA), which is accepted for medical application and widely used as a material for surgical suture, orthopedics, and traumatology products and is also a carrier for drug delivery [ 23 ]. It is important that PLGA degrades in aqueous media in vitro and in vivo and forms lactic and glycolic acid monomers metabolized in the Krebs cycle [ 24 , 25 ].…”

Implications of Quenching‐to‐Dequenching Switch in Quantitative Cell Uptake and Biodistribution of Dye‐Labeled Nanoparticles

“…reported an increase of the overall average fluorescence intensity of their dye‐loaded PLGA NPs in the presence of FBS, [10] as PLGA can be degraded by both acidic pH and enzymes in cells, as well as salt, serum proteins and their catalyzing effect [22] . Temperature also plays a critical role in PLGA degradation, and the elastic modulus of PLGA NPs was found to decrease significantly in water at 37 °C [23] . The swelling and/or degradation mechanism of PLGA NPs in FBS could also be explained by the adsorption of serum proteins onto the NP surface thus reducing the stability of particles [24] .…”