Strategy for Synthesis of Statistically Sequence-Controlled Uniform PLGA and Effects of Sequence Distribution on Interaction and Drug Release Properties

Abstract

Extensive studies have been conducted to elucidate the effects of such parameters as molecular weight, polydispersity, and composition on the controlled release properties of poly(D,Llactic-co-glycolic acid) (PLGA). However, studies dealing with the effect of monomer sequence distribution have been sparse mainly because of the difficulty of precisely controlling the monomer sequence in PLGA. Herein, we present a semibatch copolymerization strategy that enables the production of statistically sequencecontrolled "uniform PLGA" polymers through control of the rate of comonomer addition. Using this method, a series of PEG− PLGA samples having a comparable molecular weight and composition but different sequence distributions (uniform vs gradient) were prepared. The properties of these materials (PEG crystallization/melting, hygroscopicity, aqueous sol−gel transition, drug release kinetics) were found to significantly vary, demonstrating that sequence control only at the statistical level still significantly influences the properties of PLGA. Most notably, uniform PLGA exhibited the more sustained drug release behavior compared to gradient PLGA.

cRGD-targeted gold-based nanoparticles overcome EGFR-TKI resistance of NSCLC via low-temperature photothermal therapy combined with sonodynamic therapy

“…The drug release rate was higher in the acidic environment, due to the fact that the PLGA polymer compound encapsulating the drug was more stable in a neutral environment, while it was easily hydrolyzed under acidic conditions. 38 The rate of drug release was generally consistent with the findings of Zeng et al 39 The low pH of the tumor microenvironment facilitates the release of drugs in the tumor region. The amount of gefitinib release from cRGD-GIPG NPs significantly increased to 76% after irradiation with 808 nm laser (0.5 W cm −2 , 5 min) for 6 h at pH = 5.0 (Fig.…”

Radiation-induced photodynamic therapy using calcium tungstate nanoparticles and 5-aminolevulinic acid prodrug

“…For SEM, 20 μL of CWO or PEG–PLA/CWO NPs (0.1 mg mL −1 based on CWO mass) in Milli-Q water was dried on a Si wafer and coated with Pt under vacuum before imaging on a Nova NanoSEM 450. 21…”

“…For SEM, 20 μL of CWO or PEG-PLA/CWO NPs (0.1 mg mL −1 based on CWO mass) in Milli-Q water was dried on a Si wafer and coated with Pt under vacuum before imaging on a Nova NanoSEM 450. 21 The hydrodynamic diameters of bare and encapsulated NPs were obtained using dynamic light scattering (DLS, Brookhaven Instruments NanoBrook 90Plus PALS). Measurements were taken at 25 °C, with a set duration of 3 minutes and averaged across 5 readings.…”

Effect of Paclitaxel Stereochemistry on X-ray-Triggered Release of Paclitaxel from CaWO4/Paclitaxel-Coloaded PEG-PLA Nanoparticles

“…The PEG-PLA block copolymer used in this study was synthesized by ring-opening polymerization of racemic lactide using monomethoxy monohydroxy PEG (mPEG-OH, M n = 5.0 kDa) as the initiator and 1,8-diazabicyclo[5.4.0]­undec-7-ene (DBU) as the catalyst, as described in our previous publications; − DBU was used (instead of conventional tin catalysts) because DBU enables the room-temperature polymerization of LA, producing polymers with much narrower molecular weight distributions due to the absence of transesterification reactions. The number-average molecular weight of the PLA block was determined by 1 H NMR (Figure S1 of the Supporting Information (SI)) to be M n = 4.78 kDa.…”