Highly Scalable, Closed‐Loop Synthesis of Drug‐Loaded, Layer‐by‐Layer Nanoparticles

Abstract

Layer-by-layer (LbL) self-assembly is a versatile technique from which multicomponent and stimuli-responsive nanoscale drug carriers can be constructed. Despite the benefits of LbL assembly, the conventional synthetic approach for fabricating LbL nanoparticles requires numerous purification steps that limit scale, yield, efficiency, and potential for clinical translation. In this report, we describe a generalizable method for increasing throughput with LbL assembly by using highly scalable, closed-loop diafiltration to manage intermediate purification steps. This method facilitates highly controlled fabrication of diverse nanoscale LbL formulations smaller than 150 nm composed from solid-polymer, mesoporous silica, and liposomal vesicles. The technique allows for the deposition of a broad range of polyelectrolytes that included native polysaccharides, linear polypeptides, and synthetic polymers. We also explore the cytotoxicity, shelf life and long-term storage of LbL nanoparticles produced using this approach. We find that LbL coated systems can be reliably and rapidly produced: specifically, LbL-modified liposomes could be lyophilized, stored at room temperature, and reconstituted without compromising drug encapsulation or particle stability, thereby facilitating large scale applications. Overall, this report describes an accessible approach that significantly improves the throughput of nanoscale LbL drug-carriers that show low toxicity and are amenable to clinically relevant storage conditions.

Magnetic Hybrid Wax Nanocomposites as Externally Controlled Theranostic Vehicles: High MRI Enhancement and Synergistic Magnetically Assisted Thermo/Chemo Therapy

“…Solid lipid nanoparticles (SLNs) were first formulated in the 1980s and since then have been the subject of a lot of research as they present a number of advantages over other DDS. SLNs provide strong protection against drug degradation and metabolic inactivation, prevent premature cargo release, present high drug loading and encapsulation efficiency, and depending on the lipid nature they show high biocompatibility . More recently, lipid‐based DDS have been combined with other forms of nanostructures to create hybrid organic–inorganic nanocomposites.…”

“…To obtain the final mWNVs, both solutions were mixed together and ultrasonicated. The obtained formulations were stable for months in solution as measured by dynamic light scattering (DLS), or could also be freeze dried (in the presence of sucrose as a cryo‐protectant) and stored as a powder for longer periods of time. To study the effect of the magnetic loading on the final properties of the mWNVs and optimize their performance in MRI and MH, a series of samples incorporating increasing amounts of MNPs were prepared from 0 to 7 % MNPs (w/w with respect to the amount of wax; samples S0 , S1 , S3 , S5 , and S7 from now on).…”

Binary Targeting of siRNA to Hematologic Cancer Cells In Vivo Using Layer‐by‐Layer Nanoparticles

“…[18] To assemble the siRNA-LNF, equal volume of 0.5 mg mL −1 PLGA nanoparticles and 1 mg mL −1 PLA solution were mixed through a quick bath sonication process in a glass vial. Briefly, 25 mg of PLGA (acid terminated, lactide:glycolide 50:50, M w 24 000-38 000, Sigma-Aldrich) in 1.5 mL of sterile acetone.…”

Layer‐by‐layer nanoparticles for novel delivery of cisplatin and PARP inhibitors for platinum‐based drug resistance therapy in ovarian cancer

“…The free drugs were initially purified by filtration through a sterile 0.2‐μm filter membrane, followed by TFF. Final liposome purification and concentration were performed using TFF …”