Controlling Morphology and Release Behavior of Sorafenib-Loaded Nanocarriers Prepared by Flash Nanoprecipitation

Abstract

Flash nanoprecipitation (FNP) is a recent developed method featuring fast processing and simple equipment for preparing drug-carrier NPs. Herein, we prepared stable sorafenib-loaded NPs with biocompatible amphiphilic poly­(ethylene glycol)-block-poly­(lactide acid) (PEG-b-PLA) as stabilizing polymer based on FNP. The formed NPs show well-controlled size and high drug loading content compared with nanoparticles from traditional antisolvent precipitation. Moreover, drug/polymer mass ratio (D/P) and stream velocity presented as Reynolds number (Re) show strong effects on particles size and internal morphology. Low D/P ratio and Re number provide core–shell nanoparticles with drug nuclei distributed in PLA matrix, which could release the sorafenib completely but keep the polymer aggregates after the drug release. While high D/P ratio and Re number lead to grained nanoparticles with bigger size and low packing density due to the coprecipitation of the PEG blocks in the structure. The drug release of these particles is fast and typically accompanied by the dissociation of the nanoparticles. Our study demonstrates that the particle internal morphology and solute packing density are crucial factors to manipulate the drug release of the FNP nanoparticles, and the developed strategy could be widely adopted to assess drug release of FNP nanoparticles for further therapeutic applications.

Control and Preparation of Quaternized Chitosan and Carboxymethyl Chitosan Nanoscale Polyelectrolyte Complexes Based on Reactive Flash Nanoprecipitation

“…As shown in Figure a, as the flow rate increases from 1 mL/min to 7 mL/min, the radius decreases from 142 nm to around 74 nm, reaching the smallest size, and the size distribution is narrower from 0.31 to 0.24 (Figure a). When the flow rates are higher than 7 mL/min (Re ≈ 406), the size remains constant at around 76 nm, suggesting intensive mixing under these conditions. ,,, These results are consistent with the literature results observed for amphiphilic polymer NPs prepared by the RFNP method, where the NP size becomes independent at a high flow rate at a fixed polymer concentration …”

“…As shown in Figure 2d, there is a drop in light intensity on the ninth day due to the possible sedimentation of the aggregated large-size NC, indicating the instability of the NCs prepared by the conventional method. 17,26 Our results suggest that the RFNP method is more conducive to prepare small and stable NCs than the conventional method; meanwhile, it is demonstrated that nanoscale complexation occurs in different environments in these two processes.…”

“…RFNP can prevent growth and aggregation faster, thus forming relatively stable NCs. , These results are consistent with those previously reported. According to Wang et al., RFNP NPs have a hydrodynamic radius of about 74 nm and narrow size distribution, while typical precipitation particles have larger sizes and a wider size spread . We also demonstrated the effect of fast mixing on the polyelectrolyte complex NPs compared with self-assembly mixing.…”

“…Different from many manual mixing methods, flash nanoprecipitation (FNP), invented by Johnson and Prud’homme in 2003, could offer a rapid and efficient homogeneous mixing for the facile controlled preparation of NPs, − and FNP is further developed by Zhu et al − In FNP, amphiphilic diblock polymers (stabilizers) and hydrophobic active materials are dissolved in an organic phase and rapidly mixed with an antisolvent stream to produce controlled precipitation with tunable particle sizes (50–500 nm) and limited size distribution, in which supersaturation can be generated much faster than the diffusion-limited aggregation that controls NP assembly at all production scales. , Great progress has been made in the past decade to obtain various kinds of NPs via FNP, such as drugs, imaging agents, genes, structured polymeric NPs, and so on. − Different from the common FNP method forming NPs based on solvent-induced supersaturation and precipitation of stabilizing polymers and hydrophobic active solutes, Zhu et al first proposed in situ reactive flash nanoprecipitation (RFNP) and used RFNP to construct NPs through fast coupling two reactive end-capped polymers [PEG–NH 2 (methoxy–poly­(ethylene glycol)–amine) and PCL–COCl (poly­(ε-caprolactone)–acetyl chloride)] . Later, Zhu et al further developed the RFNP method, in which water-soluble polyelectrolytes could be used instead of common-used amphiphilic block copolymer to prepare NPs such as linear or branched polyethyleneimine, chitosan, and ε-polylysine .…”

One-Pot Synthesis of Small and Uniform Gold Nanoparticles in Water by Flash Nanoprecipitation

“…Product properties can obviously be tuned by means of experimental parameters such as solvent/antisolvent ratio, flow rates, and concentrations of solute and stabilizer. FNP has been applied widely to prepare drug-loaded polymeric nanoparticles , because of its typical advantages: simple equipment and proper control of loading capacity and particle size by means of a simple straightforward parameter setting. By means of reactive FNP, metal nanoparticles such as Ag and Pt can be prepared (by reduction of a suitable precursor) and encapsulated in polymeric particles. − In these cases, the challenge is again to properly select the reducing and capping agents and to optimize the parameters; in literature reports so far, control over the size and size distribution of metal nanoparticles is still poor.…”