Role of self‐assembly conditions and amphiphilic balance on nanoparticle formation of PEG‐PDLLA copolymers in aqueous environments

Abstract

The production of well‐defined and reproducible polymeric nanoparticles (NPs), in terms of size and stability in biological environments, is undoubtedly a fundamental challenge in the formulation of novel and more effective nanomedicines. The adoption of PEGylated lactide (LA) block copolymers as biodegradable and biocompatible nanocarriers at different clinical stages has rendered these materials an attractive polymeric platform to be exploited and their formulation is further understood. In the present work, we synthesized a library of linear polyethylene glycol‐poly(D,L‐lactide) block copolymers with different lengths of LA (15, 25, 50, and 100 LA units) via simple and metal‐free ring‐opening polymerization, in order to alter the amphiphilic balance of the different macromolecules. The produced polymers were formulated into NPs while varying a series of key parameters in the solvent displacement process, including solvent:nonsolvent ratios and the nature of the two media, and the effect on size and stability was assessed. In addition, stability to protein–NPs interaction and aggregation was studied, highlighting the different NP final properties according to the nature of the amphiphilic balance and nanoformulation conditions. Therefore, we have illustrated a systematic and methodological process to optimize a series of NPs parameters balancing particle size, size distribution, surface charge, and stability to guide future works in the nanoformulation field. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1801–1810

Physicochemical properties and bio‐interfacial interactions of surface modified PDLLA‐PAMAM linear dendritic block copolymers

“…In order to determine how effective proteins were at binding to the surface of the aggregates, a protein binding assay using bovine serum albumin (BSA) as the model protein was performed. This study was modeled after those conducted by Pearce et al 25 Nanoaggregate suspensions were prepared at a concentration of 1 mg ml −1 using the protocol mentioned above. Following the equilibration period, BSA was added (0.2 wt%) to each aggregate suspension.…”

Polymer Pro-Drug Nanoparticles for Sustained Release of Cytotoxic Drugs Evaluated in Patient-Derived Glioblastoma Cell Lines and In Situ Gelling Formulations

“…Initial stability studies were carried out in order to mimic two common environments for nanoformulations, in particular, “control NPs” were kept at 4 °C to replicate storage of NPs in standard cool-chain conditions and the “experimental NPs” were kept at 37 °C in DMEM, replicating the physiological conditions for future in vitro work. A DLS-based assay was chosen as the screening technique due to the fast response time and ease of detection of aggregation within each sample [ 32 ].…”

2‐Methyltetrahydrofuran (2‐MeTHF) as a versatile green solvent for the synthesis of amphiphilic copolymers via ROP, FRP, and RAFT tandem polymerizations

“…NPs were prepared at a concentration of 1 mg/ml adopting a simple solvent displacement methodology (acetone/water ratio 1:5). [ 10 ] Samples were equilibrated at 25°C for 20 s prior to measurements. All experiments were performed in duplicate averaging 15 scans per run of the same sample.…”

“…[26] All the materials were able to self-assemble in water into well-defined NPs, with diameters ranging from approximately 40 up to 80 nm and PDIs equal or below 0.250 (Table 2), without the use of additional stabilizers during the nanoprecipitation step. [10] As a proof of concept, the in vitro cytotoxicity of mPEG-CL 50 and mPEG-CL 50 -LA 25 was tested on Caco-2 (intestinal), Calu-3 (airway), and THP-1 (macrophage) cells at a fixed concentration of 500 μg/ml. Both particles showed no cytotoxicity in both assays carried out in all cell types studied similarly to the cell culture medium HBSS adopted as vehicle control ( Figure S3a,b).…”

“…Aliphatic polyesters have been explored for a range of biological applications including bone and tissue scaffolds, sutures and pharmaceutical encapsulation for drug and vaccine delivery systems. [8,10,11] Specifically, the use of poly(lactide)s (PDLLA), poly (caprolactone)s (PCL), and poly(glycolide)s (PGA) and their copolymers have been the main focus for biomedical applications. [12,13] Ideally, these sets of polyesters can also be produced from biological feedstocks, making them "green" alternatives to petrochemical polymers.…”