Size-tunable nanoparticles composed of dextran-b-poly(D,L-lactide) for drug delivery applications

Abstract

Nanoparticles (NPs) formulated using self-assembly of block copolymers have attracted significant attention as nano-scaled drug delivery vehicles. Here we report the development of a biodegradable NP using self-assembly of a linear amphiphilic block copolymer, Dex-b-PLA, composed of poly(D,L-lactide), and dextran. The size of the NPs can be precisely tuned between 15 and 70 nm by altering the molecular weight (M W ) of the two polymer chains. Using doxorubicin as a model drug, we demonstrated that the NPs can carry up to 21% (w/w) of the drug payload. The release profile of doxorubicin from NPs showed sustained release for over 6 days. Using a rat model, we explored the pharmacokinetics profiles of Dex-b-PLA NPs, and showed proof-of-concept that long circulation lifetime of the NPs can be achieved by tuning the M W of Dex-b-PLA block copolymer. While the terminal half-life of Dex-b-PLA NPs (29.8 h) was similar to that observed in poly(ethylene glycol)-coated (PEG-coated) NPs (27.0 h), 90% of the injected Dex-b-PLA NPs were retained in the blood circulation for 38.3 h after injection, almost eight times longer than the PEG-coated NPs. The area under curve (AUC) of Dex-b-PLA NPs was almost four times higher than PEG-based NPs. The biodistribution study showed lower accumulation of Dex-b-PLA NPs in the spleen with 19.5% initial dose per gram tissue (IDGT) after 24 h compared to PEG-coated poly(lactide-co-glycolide) (PLGA) NPs (29.8% IDGT). These studies show that Dex-b-PLA block copolymer is a promising new biomaterial for making controlled nanoparticles as drug delivery vehicles.

Anti-migratory and increased cytotoxic effects of novel dual drug-loaded complex hybrid micelles in triple negative breast cancer cells

“…1(a)). Since a diameter of more than 7 nm was previously reported to be able to escape renal filtration and urinary excretion, this suggests that the devised micelle may potentially exhibit a prolonged circulatory half-life and enhance the accumulation of particles at the tumor site in vivo through the EPR effect [46,47]. Using FETEM, we observed that the micelles were spherical in shape and had a smooth surface ( Fig.…”

Hydrophobically-modified poly(vinyl pyrrolidone) as a physically-associative, shear-responsive ophthalmic hydrogel

“…Four samples were prepared by mixing (1) 0.5 mL of a 2.5 mg/mL solution of doxorubicin hydrochloride with 0.5 mL of PBS (drug-only control, to correct for membrane effects on release kinetics); (2) 0.5 mL of a 60 wt% C18-PVP-55kDa solution in PBS with 0.5 mL of a 2.5 mg/mL doxorubicin hydrochloride solution in PBS (to assess the effect of the associative hydrogel on release kinetics); (3) 0.5 mL of a 650 mg/mL suspension of drug-loaded nanoparticles in PBS with 0.5 mL of PBS (to assess the release kinetics achieved with nanoparticles alone); and (4) 0.5 mL of a 650 mg/mL suspension of drug-loaded nanoparticles in PBS with 0.5 mL of a 60 wt% C18-PVP-55kDa solution in PBS (to assess the combined effect of nanoparticles and the associative hydrogel on release kinetics). For nanoparticle formulations, nanoparticles based on the self-assembly of dextran-blockpoly(lactide-co-glycolic acid) (dex-b-PLGA) were produced as previously described (Verma et al, 2012), dried in vacuo, and then rehydrated at a concentration of 50 mg/mL in a solution of 50 mg/ mL doxorubicin hydrochloride in water. These solutions were sonicated for 10 min in a bath sonicator to allow the drugs to diffuse into the nanoparticles and then left stirring for three days to ensure equilibrium had been attained.…”

1,3-Beta-Glucans: Drug Delivery and Pharmacology

“…Nanoparticles are typically used in drug delivery applications because of high drug encapsulation efficiency [35], controlled drug release and incorporation of diagnostic agents [36,37]. One of the major challenges with drug delivery is achieving specificity with cellular uptake.…”

“…The amount of lysis was compared to a negative control of veronal buffered saline and positive control of deionized water. Curdlan-graft-PEG nanoparticles showed hemolysis below 5% at clinically relevant concentrations [5], which is considered biocompatible [35]. Therefore, nanoparticles and microparticles based on 1,3--glucans provide promising opportunities for drug delivery as structural units and as targeting ligands.…”